DukeMed Magazine

The Rapid Rise of Duke-NUS

Tue, 21 Jun 2011 14:20:06 -0400

This summer, the first class of medical students at Duke-NUS Graduate Medical School in Singapore officially becomes its first graduates -- receiving the first joint degrees ever to be granted by its parent schools, Duke University and the National University of Singapore (NUS).

It’s a major milestone in the short but action-packed history of Duke-NUS, which has grown in a mere six years from a promise on paper into a dynamic institution that is well on its way to becoming one of the leading medical schools in Asia.

Exceeding All Expectations

By any account, the school’s achievements are remarkable.

Since its 2005 launch, it has gone from 16 faculty and staff to more than 850, including 83 regular-rank faculty -- many of whom are internationally recognized biomedical researchers.

The student body has soared from an entering class of 26 in 2007 to 186 MD and 12 PhD students today, from 21 countries and more than 40 undergraduate institutions including Oxford, Cambridge, Johns Hopkins, Yale, Harvard, Peking University, and Stanford.

It has created robust research programs, with faculty attracting more than S$100 million (U.S.$81 million) in competitive research funding and publishing more than 370 papers in international peer-reviewed journals. The school has also generated innovative models of medical education that are drawing interest from programs across the globe.

“Duke has built many relationships with strategic partners around the world, but we will always see Duke-NUS as the crown jewel of our international activities,” says Victor J. Dzau, MD, Duke’s chancellor for health affairs. “It represents a distinctive achievement by multiple committed and trusting partners -- Duke, NUS, and the Singapore government -- that is unparalleled.”

Victor J. Dzau, MD, talks with medical students at Duke-NUS in Singapore. The school is graduating its first class this summer.

In fact, the school has zoomed past the initial goals its partners set for it, achieving milestones that had been established for its first seven years in just a little over four.

In an era when many U.S. universities are attempting to forge global academic collaborations, “Duke-NUS is a real success story,” says Michael Merson, MD, director of the Duke Global Health Institute and vice chancellor for Duke-NUS affairs. “What has been accomplished there since its founding is tremendous.”

“In terms of university partnerships on a global scale, there are not many like Duke-NUS,” agrees Patrick Casey, PhD, senior vice dean for research at Duke-NUS, who was among the school’s founding administrators. “In terms of medical school partnerships, there are none.”

Committing to Excellence

What has made the difference, he says, is commitment: “The commitment of Duke leaders, Duke faculty, leaders in Singapore -- commitment at the highest level. There were many times we could have stumbled, but everyone was committed to succeed and because of that we were able to work through the challenges.”

The commitment needed to build a medical school from scratch was no small thing. In 2000, the government of Singapore -- a city-state of 5 million people -- had launched an ambitious S$3-billion biomedical sciences initiative aimed at establishing the country as the biomedical hub of Southeast Asia.

As part of that effort, Singapore sought to create an American-style graduate-level medical school aimed at producing research-trained physician-scientists, complementing its existing British-model undergraduate medical school at the National University of Singapore.

Singapore approached Duke as a potential partner in establishing the new school based on its unique research-oriented medical school curriculum and its track record in producing leaders in academic medicine, research, industry, and clinical care delivery.

Silencing Skeptics

While the initiative was to be funded entirely by Singapore, it would require a significant investment of time and expertise from Duke.

“Many people were skeptics at first,” recalls R. Sanders Williams, MD, president of The J. David Gladstone Institutes, who served as dean of the Duke University School of Medicine from 2001 to 2007, and in 2005 became the founding dean of Duke-NUS.

“I myself wondered how on earth we could support a serious program halfway around the world when there were so many important things to do in Durham. But over time, as we got to know the remarkable people in Singapore and better envision the opportunities, that skepticism turned into excitement. We became convinced that this partnership could greatly advance medical care, education, and research not only in Singapore but also for Duke.”

“The benefits outweighed the hesitations,” agrees Rebecca Trent Kirkland, MD, a Duke University School of Medicine alumna and member of the Duke family, who served on the Duke University Board of Trustees during the years leading up to the 2005 partnership agreement and later visited the school on behalf of the Duke University Health System Board of Directors.

“We knew that some of our faculty would need to spend a good bit of time in Singapore, but we have been able to weather that and it’s actually been beneficial, as our faculty have been able to ally with NUS faculty in many areas."

"In the end, we believed that this partnership would broaden the reach of the university and provide wonderful opportunities for our students and faculty as well as the students in Singapore. It’s truly a partnership where we can grow together.”

Building an All-Star Team

As the new school took shape, so did a new world of possibilities for global collaboration. Respected Duke faculty relocated to Singapore to help get the school off the ground, including Casey and Ranga Krishnan, MB ChB, then chair of psychiatry and behavioral sciences, who would succeed Williams as dean of Duke-NUS in 2008.

They were joined by other distinguished faculty from Singapore and all over the world -- including early recruits such as Sir Colin Blakemore, former chair of the British Biomedical Research Council (comparable to the NIH), David Virshup, MD, a noted cancer researcher and pediatric oncologist, and Duane Gubler, ScD, a globally recognized infectious diseases researcher.

“We began with a few really good people and like began to attract like,” says Krishnan. “Along with the significant scientific resources available in Singapore, I believe that has been a major reason faculty have been drawn to Duke-NUS -- having strong potential partners in place for research collaborations, not only within the school but with other research groups in Singapore as well as with faculty at Duke in Durham. It’s an environment conducive to good science.”

Constructing a Cogent Curriculum

To focus the school’s efforts, leaders from Singapore and Duke early on identified five signature areas of research emphasis -- emerging infectious diseases, cancer and stem cell biology, neuroscience and behavioral disorders, cardiovascular and metabolic disorders, and health services and systems research.

Rather than being lodged in traditional academic departments, faculty have been recruited into these five specialized programs. “We identified these areas because they represent the major health needs of Singapore and Southeast Asia, while also capitalizing on Duke’s strengths in research,” explains Casey.

As notable faculty from Singapore, Duke, and all over the world have converged at the school, they have formed productive new research partnerships in those key arenas. Progress has been rapid on the education front, as well.

The school had a strong foundation to begin with, since the Duke-NUS curriculum is based on that of Duke University School of Medicine -- which condenses basic-science study into one year instead of the usual two, giving students earlier clinical experience as well as an entire year devoted to independent research.

With the fresh start in Singapore, however, leaders took advantage of the opportunity to innovate, introducing a new, technology supported model of team-based learning called TeamLEAD that’s been hailed as the future of medical education -- and a critical factor in the school’s success.

“As a faculty, we’re asking ourselves how we can promote creativity and critical thinking and how course material will actually be used down the line in the students’ professional ives,” says Doyle Graham, MD, PhD, former dean of medical education at Duke University School of Medicine, who now directs the TeamLEAD-based Body and Disease course at Duke-NUS.

“It’s the most powerful learning situation I’ve ever been in -- I consider it the highlight of my teaching career.”

Duke-NUS students have proven the power of the approach, scoring well above the mean for all U.S. medical students on both the clinical knowledge and basic science United States Medical Licensing Exams.

In 2010, the school expanded its academic offerings, opening an Integrated Biology and Medicine PhD program designed to produce leaders in translational research.

Looking Toward the Future

Although the initial 2005 partnership agreement between Duke and NUS was to last seven years, the school’s round success prompted both partners to renew their agreement early and enthusiastically, committing in November 2010 to another five-year tie-up (as it’s called in the local parlance).

“I would say that this partnership has greatly exceeded our already high initial expectations,” said NUS president Tan Chorh Chuan at the signing ceremony. “The second phase . . . promises to be even more exciting and productive.”

A primary goal for the partnership’s next half-decade is to more closely integrate Duke-NUS with SingHealth, Singapore’s largest health care group, which serves more than 4.3 million patients a year.

The school is located on the same campus as SingHealth’s 1,500-bed Singapore General Hospital as well as national heart, cancer, and other specialty centers, providing fertile ground for collaboration, says Krishnan.

“Our faculty and students are already deeply engaged in these institutions. Many of our faculty serve on their medical staff, our students perform clinical rotations there, and we work together to conduct clinical research.”

For example, he notes, Duke-NUS helped establish the SingHealth Investigational Medicine Unit, a 32-bed research unit which opened last year to conduct early-phase clinical studies. Duke-NUS also founded an Office of Clinical Sciences to provide specialized training to third-year medical students and to SingHealth clinicians interested in clinical research.

The office is led by vice dean John Rush, MD, who also serves as CEO of the Singapore Clinical Research Institute (modeled after, and in collaboration with, the Duke Clinical Research Institute).

“Our charge in phase two of the partnership is to build on this foundation to create a true academic medical center, which will help us connect research efforts inside the school to clinical care delivery and develop next-generation treatments and technologies,” Krishnan says.

Already, Duke-NUS and SingHealth leaders have worked together to create academic departments within SingHealth institutions. Graduate medical education is also being strengthened; recently, the U.S. Accreditation Council for Graduate Medical Education (ACGME) established a new international arm that is working with Singapore’s Ministry of Health to accredit 38 residency programs at SingHealth and other Singapore hospitals by 2012.

These are the first residency programs to be accredited by ACGME International standards, says William E. Rodak, PhD, ACGME-I’s vice president for international accreditation. “We’re contributing to improving graduate medical education outside of the United States and in turn, health care in other parts of the world,” he says.

The new programs will provide the next step for this summer’s graduating class, almost all of whom will complete residency training in Singapore. “These are wonderful students, and they will be excellent physicians -- bright, accomplished, committed to service, and with a truly global perspective,” Krishnan says. “We can be very proud of them as the first to graduate under the Duke-NUS banner.”

“The graduation gives us an opportunity to pause and truly appreciate the success of this venture,” adds Kirkland.

“It makes me think of the words of the Indenture that originally established Duke University, which called us to ‘provide real leadership in the educational world’ and to teach what would ‘most help to develop our resources, increase our wisdom, and promote human happiness.’ Well, with Duke-NUS, that’s just what we’ve done.”

Research with a Global Reach: Duke-NUS

Tue, 28 Jun 2011 09:15:58 -0400

The opening of Duke-NUS has opened up new opportunities for researchers in both Durham and Singapore to advance biomedical science on a global scale.

Nearly a third of Duke-NUS faculty hold joint appointments at Duke, and many other Duke faculty have taken advantage of the rich possibilities for collaboration with scientists on the other side of the world.

“Singapore is an appealing place to conduct research,” says Patrick Casey, PhD, senior vice dean for research at Duke-NUS.

“The country has made a tremendous investment in biomedical science, which has attracted top researchers internationally and provided opportunities to access unique technologies, such as a chronobiology suite for sleep research that’s one of the few of its kind in the world. Singapore also offers access to a well-annotated patient population with different ethnicities and lifestyles than in North Carolina, so it’s a great place to conduct comparative clinical studies.”

Among the dozens of Duke-Singapore collaborations to date include research focused on:

Dengue fever: A team of researchers at Duke and Duke-NUS led by Mariano Garcia-Blanco, MD, PhD, used gene silencing technologies to identify dozens of proteins the dengue fever virus relies on identifying promising new targets to develop antiviral drugs for the devastating mosquito-borne disease.

Dengue has been one of the first major research concentrations of Duke-NUS; the school’s program in infectious diseases is led by Duane Gubler, ScD, considered the world’s foremost expert on dengue fever.

Metabolic disorders: Duke-NUS’s Scott Summers, PhD, is studying how a type of lipids called ceramides contributes to the development of insulin resistance and diabetes, working with Christopher Newgard, PhD, of Duke’s Stedman Nutrition and Metabolism Center

Parkinson’s disease: Tso-Pang Yao, PhD, of Duke’s Department of Pharmacology and Cancer Biology, and Kah Leong Lim, PhD, of Duke-NUS and Singapore’s National Neuroscience Institute, have elucidated the role of certain disease-causing mutations in the Parkin gene -- contributing to understanding of the causes of neurodegeneration in Parkinson’s disease.

Aging: Researchers Angelique Chan, PhD, of Duke-NUS and Truls Ostbye, MD, PhD, have conducted population-based and longitudinal studies related to the care and well-being of the elderly in Singapore, one of the most rapidly aging countries in Asia.

Sleep deprivation: Neuroscientists led by Michael Chee, MD, of Duke-NUS and Scott Huettel, PhD, of Duke’s Center for Interdisciplinary Decision Science found that sleep deprivation can alter strategic preferences in risky decision-making -- increasing sensitivity to gains while decreasing sensitivity to losses.

These global collaborations are just a start; over the past year, Duke and Duke-NUS have hosted a series of symposia that bring faculty from Duke and Singapore together to discuss shared research interests and generate ideas for joint projects in areas from heart disease to health services research.

In addition, more than 50 Duke and Duke-NUS faculty have joined a new Duke Cardiovascular Research Center established to advance global basic research objectives. The center is led by Thomas Coffman, MD, chief of Duke’s division of nephrology, who also directs Duke-NUS’s Cardiovascular and Metabolic Disorders research program.

“The ties between Duke and Singapore provide a unique opportunity to bridge researchers who are literally a half world apart,” he says. “We hope to create an environment that amplifies the quantity and quality of research across both campuses.”

See page 12 of the Summer 2011 issue of DukeMed Magazine (PDF, 5 MB) to learn more about the graduates of the Duke-NUS class of 2011.

Leading with TeamLEAD: An Innovative Curriculum at Duke-NUS

Mon, 27 Jun 2011 16:27:15 -0400

From the prime minister of Kazakhstan to representatives from Harvard, more than 100 delegations from all over the world have visited Duke-NUS to learn more about the school’s innovative approach to medical education.

Called TeamLEAD (learn, engage, apply, develop), the method is a radical departure from traditional lecture-based teaching formats. Instead, students are responsible for learning the bulk of the material before class, using recorded lectures from Duke University School of Medicine along with reading assignments from textbooks and medical journals.

Once in class, they are tested both individually and in small groups, so instructors can focus the rest of the session on areas of weakness. The teams then work together, with “open-book” access to medical references, to solve clinically oriented questions related to the material.

“The best doctor is no longer the doctor with the best memory,” says Robert Kamei, MD, vice dean for education at Duke-NUS. “In an age when information is available anywhere, instantaneously, we want to provide students with the skills they’ll need in the future -- the ability to find the latest information and apply it to clinical practice.

To succeed at the highest level, they need to be able to both work in teams and provide leadership, so our curricular approach focuses on developing those abilities, not just rote memorization.”

Although the concept of team-based learning was introduced in business schools in the 1980s, TeamLEAD is the first time it has been adapted for medical education.

“It’s difficult to introduce a whole new approach within an existing school,” says Ranga Krishnan, MB, ChB, dean of Duke-NUS. “In Singapore we had the opportunity to ask ourselves, with everything we know now about medicine, research, and teaching, what is the best way to train our students?”

“There are significant advantages to the TeamLEAD approach,” agrees Edward Buckley, MD, vice dean for education at Duke medical school, who helped develop the Duke-NUS curriculum. “It makes more efficient use of the instructor’s time and is better suited to the way adults learn, which is by applying new information in a practical context. It’s also very good preparation for clinical practice, which is increasingly moving toward multidisciplinary, team-based care.”

In fact, the approach is now being adopted in pilot programs at “Duke Durham,” as the U.S. school is known in Singapore. This year, first-year medical students in the Brain and Behavior, Molecules and Cells, and Body and Diseases courses participated in team-based learning exercises, and “we plan to adapt more of the methodology going forward, especially after we move into our new Learning Center,” says Buckley.

“The opportunity to exchange these kinds of ideas and share experiences is a very rich and rewarding part of this partnership.”

See page 12 of the Summer 2011 issue of DukeMed Magazine (PDF, 5 MB) to learn more about the graduates of the Duke-NUS class of 2011.

The Brain Electric: Deep Brain Stimulation for Neurologic Disorders

Thu, 23 Jun 2011 09:17:17 -0400

Rigid posture, tremor, postural instability, shuffling gait. These are the technical terms you might apply to the man with advancing Parkinson’s disease as he struggles to descend the stairs outside his front door and staggers down his driveway, shoulders hunched, balancing himself precariously between his cane and the car door as he makes his way toward the mailbox at the end of the drive.

The same man on the same day, with his brain stimulator turned on, can walk down the stairs while putting on his jacket, step easily into his car, and drive to the post office. If you saw him on the street, you wouldn’t know he was sick at all.

“It’s a striking outcome, but it’s by no means unusual,” says Duke biomedical engineer and neuroprosthetics expert Warren Grill, PhD.

Brain stimulators, which are devices that deliver steady electrical currents to certain structures in the brain, have been implanted in more than 80,000 patients worldwide. Most commonly used to suppress the symptoms of severe tremor and some cases of Parkinson’s disease, brain stimulation was also recently approved by the FDA for use in medication-resistant obsessive-compulsive disorder.

It’s being explored for treatments of other brain-born illnesses as well, such as epilepsy and depression.

Brain stimulation offers an alternative to medical therapies, which work mostly to block or boost the release and uptake of chemicals that affect neural function. But the brain is an electrical organ as well as a chemical one, and the field of brain stimulation seeks to explore and expand the use of electrical current as a tool for treating disease.

It may even improve the understanding of how the brain does what it does, so that we may better fix it when something goes awry.

Biomedical engineer Warren Grill is investigating ways to improve DBS technology.

The Perks

In deep-brain stimulation (DBS), electrodes are implanted into carefully chosen places in the brain -- for Parkinson’s disease the subthalamic nucleus, an almond-sized structure in the middle of the head, is the usual place -- and a battery-operated pulse generator, implanted just below the clavicle, delivers a steady electric current of about 130 pulses per second through the electrodes.

When the physician finds the right spot and the right frequency, the symptoms go away.

“Unlike with ablation, you’re not killing any tissue when you use DBS -- so you can undo it at any time -- and you can modulate the frequency of the current,” says Duke neurologist Mark Stacy, MD, who along with fellow Duke neurologists Burton Scott, MD, PhD, and Julia Johnson, MD, refers eight to 10 patients a month for the surgical procedure.

The impact on patients’ quality of life can be astounding, especially after medical therapies have failed. “In the people whom you know are going to do well, it’s exciting to know they’re going to have their lives changed,” says Stacy.

Some patients with essential tremor or dystonia don’t get any relief from medication, so for those patients DBS is a real lifeline.

In Parkinson’s patients who do respond well to their medication, DBS can be an excellent extender of treatment, especially after these patients see the inevitable drop in the effectiveness of the drugs. For them, DBS is a way to turn back time; Stacy says it takes the clock back about five years in terms of motor-control symptoms.

DBS does not replace medication in Parkinson’s patients -- it works synergistically with their medication to provide more functional hours in the day.

“As your medicine works, your symptoms ebb and flow,” explains Stacy. “Levodopa [the most commonly prescribed drug for Parkinson’s patients] has a four-hour time of benefit, and it’s very difficult to be on such a tight dosing schedule.”

And since any variability leads to mobility problems, it’s almost impossible to prevent this ebb-and-flow effect. DBS allows these patients to stay better longer, with far fewer interruptions in motor function. Other patients may begin having significant side effects from medication over time.

Stacy was the first person to identify a particularly troubling side effect of the class of drugs -- dopamine agonists -- that are used in Parkinson’s patients: impulse control disorders such as compulsive gambling or other high-risk compulsive behaviors.

In about 15 percent of patients, the dopamine effect leads to behavioral problems that are significant enough to make staying on the drugs a practical impossibility. For these patients, DBS is also an ideal option, says Stacy.

“The effect of DBS treatment on tremor is the most dramatic, but treatment of Parkinson’s may be the most rewarding, because these people have real mobility problems, and with treatment their mobility problems improve.”

Mechanisms Unknown

According to Grill, DBS is “the closest thing I’ve seen in my life to a miracle.” But, in typical miracle fashion, it has yet to be explained -- no one knows why stimulation of the brain causes these dramatic changes to occur, and there’s still much disagreement about what’s going on.

The debilitating spasticity and rigidity of bodies that suffer from brain disorders such as Parkinson’s disease, essential tremor, and dystonia come from highly organized neural firing patterns that interrupt the brain’s ability to generate normal movement in the body.

In Parkinson’s disease, for reasons still unknown, cells in the basal ganglia that produce dopamine begin to die; as levels of dopamine drop, neurons start to fire in synchronous bursts, “like a popopopop,” says Grill. “In a normal brain, there are very few of these kinds of firing patterns.” DBS somehow disrupts the pathologic popopopop.

“We’ve done a good job of eliminating some hypotheses about how DBS works,” says Grill, such as the early thinking that the neurons were being blocked by the artificial electrical current. Grill theorizes that the stimulated neurons are firing in lockstep with the DBS, which prevents those neurons from transmitting any information.

That’s because neural communication is like vocal communication in this way, says Grill -- it’s not just the sound of your voice but the modulation of that sound that creates meaning, which is why we talk and sing instead of just drone to one another.

Grill says the same concept is at work in neural communication, and DBS locks an otherwise misfiring neuron into a sort of neural monotone, shutting down the pathological popopopop.

Grill wants to understand how DBS works because he wants to improve it. For example, like any treatment, DBS has a “dose” -- an optimal frequency, somewhere between 100 to 200 pulses per second, to control the patient’s symptoms with minimized side effects -- and the physician has to program the output.

But for DBS, the number of potential doses is enormous. There are 30,000 possible parameters, Grill says, and which dose will work best for which patient is hard to know. While the side effects of DBS are generally preferable to those of medications, and certainly preferable to the symptoms themselves, they are not negligible.

“Some side effects are overt: unwanted movements, especially in the eyes; disruptions in speech; problems talking, swallowing, or walking,” says Grill. “Also there are more subtle, less understood cognitive side effects, such as decline of verbal memory and changes in mood.”

The side effects are exacerbated at higher frequencies -- as is battery consumption. Most DBS patients have to have their batteries replaced every four years or so; and when a battery costs $25,000 and requires a surgery to replace, prolonging its life is especially valuable.

“If we could figure out how to achieve symptom control at 50 pulses per second instead of 130, we could reduce both battery consumption and side effects,” Grill says.

His team is developing computer models of new lower-frequency firing patterns. After testing them in rat models Grill works with Duke neurosurgeon Dennis Turner, MD, to take those experimental models into humans as quickly as possible, through a unique testing protocol in patients who have to come in for their battery change.

During the window in which these patients are “unplugged” from their current device, Grill can test his models. This has been done in about 60 patients so far, and the group is also working with Emory and Wake Forest universities to add to the patient pool.

“It’s been a really productive approach to getting our discoveries into humans quickly,” Grill says.

Noise in the System

Miguel Nicolelis, MD, PhD

Duke neurobiologist Miguel Nicolelis, MD, PhD, offers a different explanation for how brain stimulation works: he believes that electrical stimulation disrupts the misfiring neurons’ synchronous pattern, to get those cells off phase and restore the chaos that the brain needs in order to initiate movement.

“The pathological signal in Parkinson’s is very organized,” he says. “It’s like hearing a pure tone.” If their rhythm were drawn on a computer screen, the misfiring neurons would pile up on top of each other, making one big sine wave.

And though a sinus rhythm might look good on a heart monitor, the brain needs less organization in its neurons in order to organize movement in the body.

“The brain likes chaos,” he says. “So we’re inserting noise to disorganize the brain, because that’s how the brain gets things done.”

More important, Nicolelis believes that instead of targeting the brain itself, electrical stimulation may be more effective if it’s delivered to the spinal cord.

Spinal cord stimulation, in which the electrical current is delivered to the top of the spinal cord, has been used since the 1960s for treatment of pain -- in fact, deep brain stimulation as a technology was originally developed for pain patients who didn’t respond to spinal cord stimulation.

Nicolelis’s team has conducted successful studies of spinal cord stimulation in mice with depleted dopamine and Parkinson’s symptoms, which showed that the technique disrupted those symptoms.

The team is currently finishing studies of the technique in primates; based on preliminary results from those trials, Nicolelis expects to start human trials of his spinal cord stimulation protocol as early as 2012.

The concept for the spinal cord stimulation device came from “a moment of sudden insight,” Nicolelis explained when the results of the rodent study were published in Science in 2009.

While analyzing the brain activity of mice with symptoms of Parkinson’s disease, Nicolelis was reminded of some research he’d done in the epilepsy field a decade earlier. The rhythmic brain activity he saw in these animals resembles the mild, continuous, low-frequency seizures that characterize some types of epilepsy in humans.

One way to disrupt the seizure activity in some epilepsy patients is to stimulate the peripheral nerves, which conduct communication between the spinal cord and the limbs, so Nicolelis applied the same concept to Parkinson’s.

“In our studies, we found that the synchronous firing of neurons occurs in different locations throughout the brain,” Nicolelis says. He calls the brain’s normal electrical signals a symphony with no maestro -- our thoughts and behaviors arise from neural firing that takes place across multiple brain structures.

“While the motor cortex is probably where most of it is happening, the spinal cord has access to all structures in the brain,” making it the best location for stopping any bad signaling from the brain. “Also, accessing the spinal cord is much less invasive, it’s easier to do, and it requires less battery power.”

All this means it’s also much more affordable; Nicolelis says it would be so cheap that DBS for movement disorders might become obsolete.

A Future Unknown

Dennis Turner, MD

Turner agrees that, although DBS is an esoteric surgery, its main problem is not its invasiveness, but its cost.

Except for the United States, France, and Germany -- countries where it’s covered by insurance -- it is a self-pay or charity-pay procedure, with the bill being around $120,000 (plus a cool $25,000 every four years for battery replacement).

“It’s a real question, then,” he says. “Is it a lasting therapy if it’s something that most people in the world, even in developed nations, cannot afford?”

Even in the United States, where DBS is covered by insurance, about three-fourths of Parkinson’s and tremor patients who are good candidates don’t want it. Because, well, it’s brain surgery.

Turner’s proficiency at this procedure keeps his patients’ complication rates very low, but as he says, “they’re not zero. And we try hard not to minimize these risks, so that people have an honest view of what they’re getting into.”

Most neurologists are reluctant to recommend brain surgery, says Turner, citing epilepsy as a good parallel example -- for an epilepsy patient, their disease is not degenerative like Parkinson’s, so effective symptom control could be almost like a cure.

“There have been several NIH consensus conferences where everybody agrees that after about two years, if the epilepsy patient isn’t responding to medication, they should be referred for surgical treatment. But the actual time to referral for surgery averages at 17 years. Elective surgery for things that are chronic is not easy for most people, even physicians, to swallow.”

People who do choose DBS tolerate it very well, Turner says, because DBS is imperceptible to the patient after implantation. But Grill, Turner, and Stacy all emphasize that DBS is not a curative procedure.

The specific symptom control that the device offers is durable, says Turner -- for patients with degenerative diseases such as Parkinson’s, motorcontrol symptoms don’t get worse -- but other symptoms (dementia, balance problems) will progress, because the brain is continuing to die around the device.

“DBS works very well,” says Turner. “It’s very successful, but everybody would really rather treat the disease than the symptom. Most of the efforts to treat Parkinson’s still focus on approaches such as cell therapy or gene therapy.”

According to Turner, the closest idea to a cure is gene therapy -- he and Stacy are among several teams working on clinical trials of gene therapies that can produce a lifelong improvement in the neurons that are degenerating in Parkinson’s diseases.

“These are the most promising approaches right now -- meaning we could have possible FDA approval within less than five years,” he says. “That would ultimately be much more satisfying, to find a single treatment that’s lasting.”

Nicolelis suggests that in the future, the use of electrical current could be a similarly lasting therapeutic tool.

“We want to pursue the idea that by disrupting this pathological signal you could somehow disrupt the degenerative process. Think of it as a feedback loop -- cells die, which causes more cells to die. By altering this pathological pattern we might allow some cells to survive, or to even slow down the process as a whole. We don’t have proof of this yet, but that’s a theory we want to explore.”

According to Nicolelis, all neurological disorders -- and psychiatric disorders -- can be treated as diseases of timing. “It’s the timing of neuronal firing that’s key. The only difference among all these diseases is where and how this timing acts on the brain. So correcting the misfiring of neurons might be the most essential treatment in any neurological disorder -- and it might be that electricity is the key.”

Is DBS an Option for your Patient?

Stacy says DBS can make a big difference in patients with advanced tremor or idiopathic Parkinson’s disease (PD), but it’s important to identify the right patients for the procedure.

Physicians might consider referring their patients who meet the following criteria:

Tremor patients: poor response to medical therapy
PD patients: Levodopa responsive, with good “on” period function
Troublesome symptoms, despite optimized pharmacotherapy:

Troublesome bradykinesia, rigidity, tremor, or gait in off periods
Unpredictable on-off phenomena
Motor fluctuations
Bothersome dyskinesia

No dementia or significant untreated depression
Realistic expectations of what the treatment can -- and cannot -- do

To refer a tremor or PD patient for a DBS evaluation, call 919-668-2493.

Not-So-Deep Brain Stimulation: Transcranial Magnetic Stimulation (TMS) at Duke

Tue, 28 Jun 2011 09:08:38 -0400

When Sarah Hollingsworth Lisanby, MD, joined Duke as the new chair of psychiatry last October, she brought with her a prodigious lab that has been instrumental in developing new devices for psychiatric disorders.

Among them is a form of brain stimulation called transcranial magnetic stimulation (TMS), which, thanks to a study led by Lisanby, earned FDA approval in 2009 as a treatment for depression in patients who have failed medical therapy.

“TMS has been around since 1985 as a neuroscience tool,” says Lisanby, and recent advances in bioengineering have allowed TMS to transition from a basic tool of discovery to a therapeutic application. It works on the principle of electromagnetic induction, through which magnetic fields induce electrical fields.

“Powerful magnets that are turned on and off very rapidly will induce a small electrical eddy current in a conducting medium,” Lisanby says -- and the fluid-filled brain is the perfect medium. There’s a network of brain areas that are underactive in depressed patients, says Lisanby.

“It’s not as crisply defined as the neural loop in motor disorders,” she says, noting the wide array of life experiences and biological pathways that feed into each individual case of depression. “But functional imaging shows us that this same network of brain areas comes up again and again in depression patients. If we can go in and change the function of these areas, perhaps we can affect depression like DBS does for motor disorders.”

Shaped like a paddle and held on the head, the magnetic coils of the TMS device send a magnetic field through the skull that stimulates an area of the brain beneath the left side of the forehead known as the left dorsolateral prefrontal cortex.

Making that area more active can reduce symptoms of depression in some patients -- in the clinical trial led by Lisanby, patients who received TMS had greater declines in symptoms (as measured by Montgomery-Åsberg Depression Rating Scale, Clinical Global Impression Severity of Illness Scale, and Inventory of Depressive Symptoms–Self-Report scores) than patients who did not.

The effects of TMS are moderate, and about the same order of magnitude as that seen with antidepressant medications, though less significant than those of electroconvulsive therapy (ECT) -- which uses much stronger electrical current to induce a brain-wide seizure in order to alleviate depressive symptoms.

Also unlike ECT, TMS is completely noninvasive; during the hour-long treatment, the patient sits in a reclining chair and does not need anesthesia. It hasn’t been found to affect memory or cognition, and the side effects -- such as scalp discomfort or headache -- are generally mild.

Typically, patients go for one-hour sessions daily for a series of weeks, and then follow up with medication or continued, less frequent TMS. The effects of the treatment also last for several months, and Lisanby says the repeated doses may help make the brain more amenable to future treatment.

“When a person does anything repeatedly, like practicing the piano or trying to memorize a sequence of behaviors, the person is repeatedly using a particular circuit,” she explains. “This is the concept of neuroplasticity: repeatedly using a circuit makes it easier to engage that circuit in the future.”

Lisanby considers TMS a solid step toward developing new and newly effective angles for treatment of depression. “Refractory depression is a very serious illness, and we need more technologies for these kinds of disorders,” she says.

“TMS is radically different from current treatments for depression, and we want physicians to know that TMS is out there as an option for patients who are suffering from depression and for whom other treatments were intolerable or ineffective.”

Lisanby and her team are also studying ways to make magnetic stimulation more effective through the induction of focal seizures. This technique, called magnetic seizure therapy (MST), was developed by Lisanby’s team and promises to retain the efficacy of ECT, the most effective treatment for depression, but without the undesirable side effect of memory loss.

Clinical trials on MST are under way now at Duke and other universities in the United States, Europe, and Australia.

Duke offers a weekend CME training on TMS that includes didactics and hands-on training. For more information, contact Rosa Jou-Zhang at rosa.jouzhang@duke.edu or visit the Office of Continuing Medical Education Web site.

To refer a patient for TMS, or for a research study involving brain stimulation, contact Lis Bernhardt at lis.bern@duke.edu or call 888-ASK-DUKE.

Rethinking Primary Care

Tue, 21 Jun 2011 15:18:26 -0400

Last year, high blood pressure, obesity, and uncontrolled diabetes were slowly killing 46-year-old Phil Smith.

He wasn’t using his insulin properly and couldn’t seem to stick to an exercise regimen or a healthy diet. There’s nothing unusual about this story so far. In fact, now that a quarter of the U.S. population suffers from chronic illnesses like heart disease, diabetes, or asthma, most providers see some version of it play out every day.

Unfortunately, caregivers too often come in only at the end of the story -- when patients show up at the doors of the clinic or emergency room with advanced disease or life-threatening complications that are both damaging to their health and extremely expensive to wrestle back under control.

In Smith’s case, though, there’s a plot twist.

Drew O’Donnell, MD, Smith’s physician at Family Medical Associates of Durham, invited him to take part in a pilot program for patients with uncontrolled diabetes. Rather than being left to manage his condition alone in between check-ups, Smith was assigned a personal care manager -- Margarette Wrenn, RN.

John Anderson, MD

Wrenn showed Smith how to keep a blood sugar diary, and now reminds him to bring it in before his scheduled doctor’s appointments. She calls Smith two weeks after each appointment to make sure he’s following his doctor’s advice.

If he’s having trouble doing so, Smith gets help from Wrenn in accessing nutrition, exercise, and behavioral counseling services and providers.

Within four months of joining the program Smith lost 25 pounds, but his blood sugar remained uncontrolled. Wrenn dug a little deeper, and discovered Smith wasn’t able to keep good tabs on his blood sugar because he couldn’t afford glucometer test strips.

“A lot of our patients don’t realize the seriousness of diabetes complications or what resources are available to them,” says Wrenn, who was able to help Smith get the supplies he needed. “They tell me things they don’t mention to their doctor. It gives them another chance to ask questions.”

This pilot program represents a whole new approach to diabetes management in the primary care setting -- and a growing effort by Duke Primary Care to take a more active role in managing patients’ health.

It’s a big change from the time when doctors simply waited for patients to come to the office, treating problems as they arose, says Scott Joy, MD, medical director of Duke Primary Care Pickett Road. “Now we work as a team to provide care that’s integrated and proactive. We’re setting up safety nets to catch our patients so they don’t fall through the cracks.”

By making preventive care more accessible and more effective, these tactics aim to help patients avoid more costly health problems down the line. They’re also drawing a road map for navigating the uncharted territory of health care reform.

“We’re entering a time that presents many opportunities and challenges,” says William J. Fulkerson Jr., MD, executive vice president of Duke University Health System (DUHS). “We’re trying to anticipate what we need to look like in five years and what we need to change in order to be successful as we move forward. Our primary care providers, perhaps more than any others, are best prepared to help us define the best care delivery models for the years ahead.”

Predicting the Future

Redesigning health care has been talked about for some time, but it’s taken on a new, pragmatic sense of urgency following passage of the Affordable Care Act last year.

Since most of the health care reform provisions in that act have yet to be implemented, no one can say with certainty what care models will eventually emerge to meet health care reform’s goals of greater access and efficiency. Nevertheless, everyone agrees that redesigning care is a necessity.

Not only are health care costs spiraling, sweeping changes in reimbursement are about to collide with an increased demand for services as 32 million currently uninsured patients are set to gain coverage under health care reform.

“A lot of indicators point to a future in which reimbursement mechanisms will shift the financial risk of caring for patients away from employers and insurers and toward providers,” says Fulkerson. Broad cuts in Medicare and Medicaid reimbursement are forecast too. “We anticipate providers will eventually be financially rewarded for delivering high-quality, low-cost care, and penalized when they don’t.”

The stage is set for a fundamental shift away from the current fee-for-service model, which pays doctors for episodes of care, diagnostic tests ordered, and procedures performed regardless of outcomes. But how and when that transformation will occur remains unclear.

A more value-driven financial model, which emphasizes quality and encourages hospitals, doctors, and other providers to work together to deliver patient care more efficiently, is the subject of much discussion in medical journals as well as in leading newspapers.

Realizing that model is the ultimate goal behind DUHS’s “top to bottom commitment and effort to redesign care,” says Michael Cuffe, MD, DUHS vice president for medical affairs. “Our mandate is to increase access to high-quality care while controlling costs,” he says.

“To do that, we need to prevent unnecessary emergency room visits, hospitalizations, and readmissions. We need to improve transitions of care between primary care, specialists, and the hospital. We need to equip ourselves to better manage different populations of patients with chronic disease. Ultimately, we need to create a more patient-centered experience.”

Home, Sweet Medical Home

That’s a tall order given that health care has traditionally been fragmented among independent primary and specialty care offices and hospitals -- with the traditional fee-for-service payment structure providing little financial incentive to coordinate care services among them.

One of the most promising models to emerge is what’s been dubbed the “patient-centered medical home.” Sometimes described as primary care on steroids, medical homes create well-oiled teams of physicians, advanced-practice providers, nurses, social workers, and other caregivers who work together to manage all of a patient’s needed care services, both within the practice and beyond its walls.

Endorsed in recent years by organizations from the American Medical Association to the National Committee for Quality Assurance (NCQA), the medical home model has its roots in pediatrics, where practices often coordinate care for children from birth though adulthood.

“We’ve always organized our patients’ medical care as well as their psychosocial care,” says Elaine Matheson, a pediatric nurse practitioner at Durham Pediatrics. “Medical homes also involve creating real partnerships between providers and patients, which has been a defining feature of pediatrics -- we involve the whole family in the decision-making process.”

An early pioneer in the medical homes movement, Duke began in the 1990s to move the concept into the adult-care arena.

“We recognized the need for a fundamental shift in the way we provided care that focused on comprehensive treatment for our patients, not just their acute situation,” says Lloyd Michener, MD, chair of the Department of Community and Family Medicine.

Realizing that the medical-homes model would need to be backed by supportive reimbursement policies, the department worked with the State of North Carolina in 1997 to pilot one of the first networks that pays care teams to coordinate health services for Medicaid patients -- $2 to $3 per enrollee per month.

Today, there are 14 networks statewide, known as Community Care of North Carolina (CCNC); estimates indicate the program has saved the state more than $1.2 billion to date. For demonstrating that coordinated care can improve the health of communities while reducing overall health care costs, CCNC is looked to as a national model for care redesign -- as are other medical-homes-based models initiated at Duke.

In 2009, the Marshall I. Pickens Clinic, part of Duke’s Division of Family Medicine, became one of the first practices in the Southeast to be officially recognized as a patient-centered medical home by the NCQA. Today, Duke Primary Care is adopting the medical home model throughout its 24-practice network, and official NCQA certification is expected soon.

Ultimately, says Duke Primary Care’s chief medical officer John Anderson, MD, “We want to create continuous, long-term, healing relationships between patients and providers, rather than episodic ones.”

Primary Care 2.0

Transforming a primary care practice into a medical home takes some rejiggering of systems and processes, of course.

Patients need ready access to their care team, and the care team has to communicate and coordinate vast amounts of information not only to their patients, but among the team and with external care providers.

Jane Satter, MD

In the Duke Primary Care (DPC) network, for example, moving toward a more patient-centered model of care has entailed major changes to make it easier for patients to get appointments when they need them.

DPC practices were the first in Duke’s health system to switch to so-called “open access scheduling” to offer patients same-day appointments, the first to extend hours to provide more urgent care and after-hours access, and the first to allow patients to book appointments online, using Duke’s Web-based patient portal (HealthView.dukehealth.org).

These changes have increased practice efficiency as well as patient and staff satisfaction, says Anderson. “By leaving substantial blocks of the primary care provider’s schedule open, we’re able to respond to patient needs when they arise -- and typically we can assign those patients to their usual provider, which improves continuity of care and enables us to take care of things like preventive screenings the patient may be due for at the same time.”

Information technology is also critical to the job of coordinating patients’ care across a complex array of providers and locations, says Anderson. Next year, Duke Primary Care will be the first group to assist in a multi-year rollout of an approximately $50-million transformation of the Duke ambulatory electronic medical records system.

The health system has also initiated an evaluation of an inpatient electronic medical record system that will standardize inpatient systems and also provide a seamless flow of information between inpatient and outpatient records. Already, DPC providers are employing IT tools to improve their ability to manage care for some patient populations.

For example, DPC has launched an electronic diabetes registry to better track care for those patients. The registry supports efforts such as the diabetes management program at Family Medical Associates by enabling the entire care team to input and view each patient’s interventions and test results.

Early data gleaned from the registry are also proving the success of the pilot program -- according to O’Donnell, more than half of enrolled patients saw improvements in their hemoglobin A1C levels, a measure of blood sugar. “That’s almost certainly due in part to our improved ability to track their progress and adjust care as needed,” he says.

Care teams are also using electronic registries to streamline patient visits. Nurses can update a patient’s medication list, perform a rapid-result A1C test, and enter the new information into the patient record before the doctor even enters the exam room.

“We have so much more information at our fingertips now,” says Jane Satter, MD, practice medical director at Hillsborough Family Practice. “In a prior era, we would have said, ‘Let’s wait and see what the lab work shows.’ Now, the lab work can often be done before I see my patient. I can pull up the results right then and adjust her medication on the spot.”

Satter says these and similar exam-related efficiencies can enhance the quality of the time she spends with her patients. “It gives us time to talk about how they can modify their lifestyle in a way we couldn’t do before.”

Reimbursing Value

Ironically enough, the decline of the fee-for-service payment structure may be what finally lends traction to widespread adoption of these collaborative, prevention-oriented models of care.

Already, Fulkerson says, insurers are showing interest in negotiating fixed prices for physicians and hospitals for bundled patient care. “If we can deliver high-quality care for less cost, we’ll share the reimbursement savings. If we can’t, we will have to share the risk of the extended costs,” he says.

Those pressures are driving a national trend toward integrated health systems, which allow pooling of resources and also control costs by improving negotiating strength with vendors and insurers. As a result, more community physicians, specialists, and hospitals are looking to affiliate with larger health systems.

While Duke’s health system has been in existence for more than a decade, it continues to grow -- particularly in primary care. Already one of the state’s largest primary care networks, Duke Primary Care has doubled in size the last five years alone. Currently, it comprises 140 providers at 24 practices in seven counties, who see a combined 470,000 patients annually.

Plans are in place to build more practices and acquire practices with highly accomplished doctors who will deliver care that is consistent with Duke standards.

The health system also plans to hire additional providers, including nurse practitioners and physician assistants, whose skill sets will enable Duke to expand opportunities for patients seeking access to high-quality care -- whether it’s provided in minute clinics, urgent care and other ambulatory sites, or primary care offices.

“It’s our responsibility as a health care system to pioneer ways to provide the right level of care at the right venue, at the right time, by the right providers,” says Cuffe.

From Duke’s perspective, having a strong primary care network is the cornerstone of its ability to provide an optimal continuum of high-quality care across the health system. “Only a fraction of patients require specialty care,” says Ted Pappas, MD, vice chair for administration in the Department of Surgery.

“But when they do, it’s essential for our system to make that care safe and seamless from start to finish.”

Integrated systems are the backbone of a new model of reimbursement called the Accountable Care Organization (ACO) -- a sort of macro version of the medical home. The concept of an ACO is to bring together providers, clinics, and hospitals into an integrated health system that works as a unit to share resources, trim costs, and boost quality care.

Although the theory has yet to be put into practice, ACOs are gaining widespread interest for what they may be able to achieve. The model “emphasizes value rather than volume,” says Anderson. “It emphasizes strengthened clinic integration across a delivery system. It requires primary care, specialty care, and hospital-based delivery models to communicate and integrate so that you limit testing and transitions of care to those that are necessary and essential.” Ideally it would cover some internal infrastructure and IT costs, he notes.

Systems would be held accountable for the quality and affordability of patients’ care, and would receive financial bonuses and share some of the savings if performance goals were met. As the employer, provider, and insurer for nearly 59,000 employees and dependents, Duke is in the unique position to take a lead in partnering with its delivery system by integrating many components of an ACO-like model into the plan design for Duke employees.

“The concepts of integrated physician networks, disease management, and aligned incentives for employees and providers are all part of our overall strategy to manage our costs,” says Kyle Cavanaugh, Duke’s vice president for human resources.

The future may be uncertain, but it’s innovations like these that will ultimately help it unfold. “Duke continues to be at the forefront of care redesign,” says Cuffe. “That will prepare us for whatever road health care reform takes.”

Primary Care 101

Mon, 27 Jun 2011 16:11:26 -0400

As one of the first medical students to participate in Duke’s Primary Care Leadership Track pilot program, Chris Danford is gaining a new perspective on how medicine is practiced.

While his peers spend most of their second year rotating through the hospital, Danford, 28, follows a set panel of patients from the hospital into the outpatient arena.

“I hear the team’s thought process while the patients are hospitalized, as well as the goals they set for long-term care,” says Danford. “After discharge, I see how much actually happens. I’m surprised at how disjointed the transition can be.”

Community-Based Learning

Showing students how the health care delivery system works through patients’ eyes is the intent of the newly launched Primary Care Leadership Track (PCLT). The four-year curriculum will require coursework and on-the-ground experiences in epidemiology and leadership training, community engagement, and the patient-centered medical home.

Students work as part of caregiver teams involved in Durham community projects such as LATCH, which serves people without insurance, and Project Access, which helps low-income patients obtain costly specialty care.

“These experiences will help our students think outside of the traditional clinical settings,” says Barbara Sheline, MD, MPH, assistant dean for primary care. “By working in the community, understanding it, and researching it, they will come to appreciate some of the current problems in the health care system and, ideally, find ways to improve it.”

PCLT -- which offers students a $10,000-per-year scholarship in exchange for committing to a career in primary care -- reflects a push by medical, nursing, and physician assistant schools nationwide to attract, nurture, and train primary care professionals -- a critical goal, given national forecasts for provider shortages across the spectrum of primary care.

Duke Medicine has been helping to lead the charge.

Last year, leaders from Duke and the University of North Carolina joined with other national health-care experts to call for dramatic changes in the way primary care is valued, delivered, and integrated into health care systems.

Their report, sponsored and funded by the Josiah Macy Jr. Foundation, stressed the need to improve educational models and advance science, teaching, practice, and policy development related to primary care as a foundation for expanding the ranks of primary care professionals.

The PCLT is one of the only such programs in the country to combine opportunities for community service with a strong emphasis on community-engaged research. It complements a revamped training program for Duke family medicine residents, which was reorganized in 2007 to emphasize community-based medicine and innovative models of care such as medical homes.

“Even before health care reform came into play, we knew some real changes needed to occur in how we care for patients and train future physicians in these new models of care,” explains Dev Sangvai, MD, chief of Duke’s Division of Family Medicine.

“We needed to enhance the way residents approach patient care, and get them thinking about health care across the continuum of needs rather than from an episodic perspective. Providers also should be thinking about their patients from a population health perspective. These approaches to patient care are generally not taught in the traditional residency model, but they are in our program.”

Duke’s highly ranked School of Nursing and physician assistant (PA) program are also making changes with an eye toward future needs in primary care.

Last fall, the nursing school received a nearly $1.3-million federal grant to help alleviate caregiver shortages by increasing enrollment and accelerating graduation rates of students in its adult primary care nurse practitioner and family nurse practitioner programs.

Similarly, Duke’s PA program won federal support this year to develop an extended primary care rotation track that will expand the number of PAs practicing in rural, underserved areas in North Carolina.

Team-Based Training

And to better prepare students for the new world of primary care, in which health professionals work as teams to coordinate patient care, Duke’s medical, nursing, PA, and physical therapy programs now offer regular team-based training sessions that bring students of various disciplines together for joint learning and problem-solving -- unmatched preparation for the future of clinical practice.

“It’s increasingly apparent that primary care will be the epicenter of medicine in the future,” says John Anderson, MD, chief medical officer of Duke Primary Care. “It’s being redefined as the career where all the action is happening.”

Read more about the new Primary Care Leadership Track on page 11 of the Summer 2011 issue of DukeMed Alumni News (PDF, 2 MB).

Living Laboratories: Duke Primary Care Practices

Mon, 27 Jun 2011 15:51:29 -0400

When the American Heart Association released new guidelines for preventing cardiovascular disease in women earlier this year, it relied, in part, on research conducted at Duke Primary Care practices.

Those studies, which investigated ways to control high blood pressure and promote physical activity and lifestyle changes, are part of a vibrant culture of clinical research within Duke’s primary care clinics.

Although patients may think of their primary care office as a place to get checkups and flu shots rather than a hotbed of cutting-edge research, primary care is actually a critical hub in the process of translating advances in medicine into “real world” practice, says Rowena Dolor, MD, director of Duke’s Primary Care Research Consortium.

“To really find out how a drug works, or if a preventive care intervention is effective, you have to test it in a busy clinical practice where the care is delivered on a daily basis,” she explains.

It is more difficult for that to take place within the walls of an academic medical center like Duke because of the highly selective population it’s designed to serve. “Less than 5 percent of community care is delivered at the hospital,” Dolor says. “Ninety percent is done in the outpatient setting by community physicians.”

DPC clinics, such as Duke Primary Care Butner-Creedmoor, which has been participating in research since the network’s inception, see patients ages one to 101. “That helps researchers collect a wide range of useful data,” says Tamra Stall, MD.

Benefits for Patients

There are benefits for patients, too. Those who choose to participate in the research gain access to new vaccines, medications, diagnostic procedures, and behavioral interventions. They are among the first to pioneer new ways to conquer obesity, lower blood pressure, manage their weight, or quit smoking.

“We look for ways to help patients to make behavioral changes and sustain that change,” says Hayden Bosworth, PhD, a Duke researcher who is a principal investigator of many studies conducted in DPC clinics.

“For example, when we studied African-Americans with diabetes and heart disease, we wanted to make sure patients understood what medicines they were taking, and we wanted to know if they were following their doctors’ orders, or what prevented them from doing so. Armed with that knowledge, we can come up with ways to effect change.”

Doctors at Duke Primary Care Pickett Road are conducting a study looking at whether knowing one’s genetic risk for diabetes will motivate patients to change their lifestyle behaviors.

“The patients want to participate,” says Scott Joy, MD, Pickett Road’s medical director. “Their interest is very high.”

The information gathered in these and other studies often leads to advances in patient care, as well as new evidence-based treatment guidelines, like those recently announced by the American Heart Association.

“The research we conduct in DPC results in publications that expert panels review for these type of guidelines,” Dolor says.

Find out about Duke clinical trials currently seeking volunteers.

Lung Cancer: Is “The Blame Game” Hurting our Progress?

Tue, 21 Jun 2011 15:58:56 -0400

Thomas A. D'Amico, MD

As a thoracic surgeon, I operate on lung cancer patients every day. We discuss life-and-death issues regarding their surgeries, but we don’t usually talk about how they feel about their disease.

At a recent lung cancer advocacy event, I had the opportunity to hear one of my patients tell her story. A former Division I soccer player for East Carolina University, 24-year-old Taylor Bell was diagnosed with lung cancer two weeks after her 21st birthday. She puts a very different face on lung cancer than most people expect.

She’s very grateful for her survival, but she says that, even when she’s talking to survivors of other types of cancer -- to anyone, really -- when she tells people she has had lung cancer, inevitably everyone asks the same thing: “Did you smoke?”

Her point of view is, “Why is that the most important thing you want to know about me?” It’s offensive to her because, number one, she didn’t smoke, and number two, what if she did? Would that mean that she deserved the disease?

Assigning Blame for Lung Cancer

That is the underlying assumption when many people think about lung cancer: In an international survey commissioned in 2010 by the Global Lung Cancer Coalition, 22 percent of U.S. respondents admitted they feel less sympathy for lung cancer patients than for patients with other types of cancer, because of the link to smoking.

The reality is that 15 to 20 percent of folks who get lung cancer have no personal firsthand experience with tobacco. Some, like Taylor Bell, are complete non-smokers. Some have been exposed to secondhand smoke, which certainly is not their fault.

If you counted just deaths from lung cancer among nonsmokers, lung cancer would still be the sixth leading cause of cancer-related deaths in the United States.

But no one should be blamed for getting cancer, regardless of their smoking history. Most smokers first start the habit as teenagers, and by adulthood it becomes entrenched; nicotine addiction is among the hardest to overcome.

The real issue is not the smoker who develops cancer; it’s how we as a society assign blame for disease. If we are to measure our sympathies for the ill by the behaviors that may have contributed to their illness, what about the patients with debilitating heart disease who have led high-stress, low-exercise lifestyles, or people with type 2 diabetes who had poor eating habits?

What about the smokers who didn’t develop lung cancer but developed breast cancer, heart disease, or stroke?

Would you have more sympathy for a smoker with lung cancer if you knew he had grown up with little education about the dangers of smoking?

What about if the individual had a strong genetic predisposition to nicotine addiction?

Stigma Slows Progress in Fight Against Lung Cancer

The truth is, it’s rare that we can draw a straight line from a person’s disease to their lifestyle choices, and applying moral judgments to the ill is not only a waste of energy, but also a slippery moral slope.

I believe the public-health campaign against smoking and tobacco use has had unintended consequences: not only stigma for the victims of diseases associated with smoking, but actually slowing our progress in the fight against those diseases. And that is something we need to pay attention to.

The fact is that lung cancer is the most important cancer disease in our country, and indeed among all developed countries, in terms of its impact. In 2010, lung cancer caused 157,300 deaths in the United States, more than breast, prostate, and colon cancer combined, according to estimates from the American Cancer Society.

In 2006, the most recent year for which we have estimates, we spent $10.3 billion in care for lung cancer patients, and the estimated loss of economic productivity due to lung cancer is $36.1 billion -- far higher than the next-highest figure (which is breast cancer, at a $12.1-billion loss).

The burden of this disease to us as a society should be, in itself, enough to compel us to do everything we can to improve diagnosis and treatment. Yet lung cancer receives much less research funding than other types of cancer that cause fewer deaths.

The stigma associated with lung cancer definitely takes its toll on survivors personally, and it’s possible that it also affects research funding for the disease. Using the most recent available data on National Cancer Institute research funding, lung cancer received only $1,875 per death, compared to $17,028 per breast cancer death, $10,638 per prostate cancer death, and $6,008 per colorectal cancer death.

It’s impossible to read the minds of people who make decisions regarding funding for lung cancer research, but I think funding disparities can be attributed partly to a combination of the smoking stigma and ageism. If a 73-year-old person has a life-threatening disease, that’s not perceived as being as important to society as a disease that affects younger people. And an older patient population also means less patient advocacy.

The fight against breast cancer, for example, has been promoted successfully because many young women who are survivors have their life to give to raising awareness. The cure rate for lung cancer is much lower than for breast cancer. So there are fewer advocates.

Need for New Screening Methods and Biologic Therapies

There is a need for greater research funding to advance two priorities that could make a significant difference for patients with lung cancer -- perfection of screening methods to catch more cases in the early stages, and stepped-up evaluation of biologic therapies, which can be equally as effective or more effective than chemotherapy without the overall toxicity.

Improved screening is an urgent need. Today, only about 20 percent of lung-cancer cases are caught at stage one. If we could increase that to 40 percent, we would improve survival dramatically.

Spiral computed tomography (CT) scan screening is a promising technique that’s being tested for patients known to be at high risk, but as a widespread tool, even CT has a drawback: the high chance of false positives.

Your CT scan might show a little nodule, but that does not necessarily mean you have lung cancer, and follow-up testing for lung cancer is invasive: if you have a positive screening for a mammography, you get a needle biopsy, but a positive screen from a CT scan might lead to a surgery.

We would like to be able to determine your true cancer status without having to do additional CT screens on you for the next five years or subjecting you to an unnecessary lung biopsy.

A line of research that holds much promise is perfecting a method for combining CT scans with a serum or urine test that detects a protein or other biomarker.

Even if we improve diagnosis, we’ll always have people who present with advanced disease, and the cure rate for those people is, frankly, dismal. One way to improve that rate is with better targeting of biologic therapies.

Industry is producing these agents faster than we can test them. We need to put more effort into testing and enhancing these agents -- which could improve treatment for others cancers as well. For instance, Avastin (bevacizumab) is now known to be successful against lung cancer, but it wasn’t originally conceived as a lung cancer agent.

To carry out these research priorities, we must erase the stigma that accompanies lung cancer and give the disease the full research support that its sufferers and their families deserve.

In the meantime, we will count on survivors such as Taylor Bell, who handles the smoking question with grace. After she tells people that no, she never smoked, the second question usually is: “Well, how did you get it?” Her response: “Why does anyone get cancer?”

Thomas A. D’Amico, MD, is a professor of surgery and director of the Duke Cancer Institute’s lung cancer program. He was elected chair of the National Comprehensive Cancer Network board of directors in 2010.

CT Screening for Lung Cancer

Fri, 01 Jul 2011 12:16:13 -0400

For the first time, people at high risk for lung cancer will have access to screening that uses computed tomography (CT) scans.

Preliminary results from the National Lung Screening Trial, released in November 2010, showed that among people at high risk for lung cancer, those who were screened with low-dose spiral CT scans showed a 20 percent reduction in lung-cancer-related mortality compared to those who were screened with standard chest x-rays.

The trial, which Duke did not participate in, included 53,000 participants ages 55 to 74 who were current and former heavy smokers.

“Once those results are published, it will be the first U.S. trial to show in a randomized fashion a benefit from screening people at high risk for lung cancer with low-dose CT scans,” says thoracic surgeon Thomas D’Amico, MD. “Before, CT screening was not thought to be effective. This is an important advance.”

Published results will likely result in third-party payers such as insurance companies and Medicare covering CT scan-based screening for patients at high risk. Right now, such screening is not covered.

Duke is currently developing a lung cancer screening program using CT scans for patients at high risk, to be launched later in 2011.

Infection Control: High-Tech Cleaning of High-Touch Surfaces

Tue, 21 Jun 2011 16:05:05 -0400

A device resembling a tall, slender R2-D2 from Star Wars bathes a room in blue light, which streams through the blinds into the hallway of the patient care unit. Inside ensues a battle of good versus evil, light versus infection.

“This is a new, big thing,” says Duke’s Luke Chen, MD. Chen is co-investigator of a study that will test the effectiveness of standard chemical cleaning practices compared to standard chemical cleaning plus a new ultraviolet light technology for cleaning hospital rooms and reducing the spread of health-care-associated infections.

“This portable ultraviolet light device creates a radiation sea that can clean almost all surfaces in a room in 20 minutes,” says Chen. “In the case of hardier bacteria like C. difficile, the cleaning takes approximately 40 minutes.”

The technology is part of a Duke study funded by a $10-million grant from the Centers for Disease Control and Prevention’s Prevention Epicenter Program, which supports efforts to develop and test innovative approaches to reducing infections in health care settings.

The ultraviolet light devices, called Tru-D (for total room ultraviolet disinfection), will be placed in the rooms of patients (after they’ve been discharged) who had contagious conditions or infections due to drug-resistant organisms like MRSA.

Investigators use fluorescent markers to identify high-touch areas in hospital rooms, such as bedrails. Afterwards, black light is used to assess how well the room was cleaned.

“We know that cleaning in a hospital is important, but the actual methods and techniques have been poorly and inadequately studied,” says Daniel J. Sexton, MD, principal investigator of the study and director of the Duke Infection Control Outreach Network (DICON), a collaboration between Duke and 39 community hospitals focused on improving infection control programs.

This method will be utilized in several DICON-affiliated hospitals, Duke University Health System hospitals, UNC Hospitals, and the Durham VA Medical Center. The information gained from using these new cleaning methods will be applied in DICON hospitals and could potentially impact other hospitals across the country.

“Prior small-scale studies suggest objects in patient rooms, such as television remotes, bedrails, and equipment, commonly become contaminated with bacteria,” says Sexton.

“We have to be certain that these items are clean when a new patient enters the room in order to reduce the risk of spreading infections. A study like this is every bit as important as a study of safety in a Boeing 747.”

Considering a New Weight-Loss Cocktail: Q&A with Kishore Gadde, MD

Tue, 21 Jun 2011 16:08:50 -0400

Kishore Gadde, MD

Kishore Gadde, MD, director of Duke’s obesity clinical trials program, talks about the promising results of a recent multicenter clinical trial that showed a new combination of existing drugs may help some patients who are struggling with obesity.

What’s the story of this trial in a nutshell?

We showed that a combination of phentermine and topiramate, drugs which are already approved to treat obesity (phentermine) and migraine and epilepsy (topiramate), achieves about 19 more pounds of weight loss than placebo -- or up to a 10 percent weight loss -- in obese people over the course of one year.

The participants who took the combo also showed significant improvements in blood pressure, blood sugar measurements (hemoglobin A1C), cholesterol, triglycerides, and inflammatory markers, including C-reactive protein.

Is this drug combo an improvement over orlistat?

The drug combo appears to be more effective than orlistat, which is the only drug currently available for the long-term treatment of obesity.

Meta-analysis studies have shown that treatment with orlistat, at maximum strength, can lead to approximately seven-pound greater weight loss than placebo after one year.

How does the drug combination work?

We believe it works mainly by reducing hunger and increasing satiety. Phentermine increases the release of norepinephrine, a brain chemical that may influence hunger and satiety.

Topiramate has numerous mechanisms of action including effects on sodium channels, glutamate and GABA transmission, and carbonic anhydrase inhibition, although the mechanism responsible for weight loss is not clearly known.

There may also be an independent effect on glucose control: More patients on placebo developed diabetes during one year than patients who were on the combination drug. More patients on the combination drug were also able to reduce the number of their diabetes and blood pressure medicines.

This study was funded by Vivus, which is seeking FDA approval to market the combination therapy under the trade name Qnexa. In October 2010, the FDA asked the company for more safety data. Why, and does this study satisfy those concerns?

In March, the FDA issued a warning regarding the use of topiramate during pregnancy, stating that pregnant women who take the drug are at increased risk of having babies born with cleft lip or cleft palate.

Thirty-four women became pregnant while in Qnexa clinical trials, and no birth defects were reported for the babies born -- but pregnant women would not be candidates for use of this drug; there is no reason for women to use weight loss drugs while they are pregnant or trying to become pregnant.

What other patients should not take this drug?

Topiramate has also been associated with memory problems and mood changes, including depression and anxiety, and we did see a dose-specific increase in depression and anxiety during the study.

Though the overall incidence of these events was relatively small, it’s still something to consider in terms of which patients are good candidates for this formulation.

Why are you excited about this drug?

This kind of weight loss, coupled with significant reductions in heart and metabolic risk factors, could be an important advancement in the management of obesity.

Two-thirds of Americans are overweight or obese, and for obese patients who have failed to achieve meaningful weight loss with diet and exercise, we have just one available drug -- orlistat -- to try before jumping to bariatric surgery. We need more treatment options that work via different mechanisms.

The 56-week, phase 3 study was conducted in 93 U.S. centers with 2,487 patients who had a BMI of 27 to 45, and two or more comorbidities such as diabetes, hypertension, and high triglycerides.

Patients in the study also received diet and exercise advice in addition to the drugs.The study was published in April in Lancet. Gadde was a paid consultant to Vivus until 2008.

Patch Work: Building New Heart Tissue -- From Scratch to Patch

Wed, 22 Jun 2011 10:04:01 -0400

Imagine a patch -- made of fully functional cardiac tissue -- that could safely and effectively restore function to heart muscle injured by a heart attack or plagued by an arrhythmia.

This is the work of Duke biomedical engineer Nenad Bursac, PhD, and his team in the Cardiac Electrophysiology and Tissue Engineering (CETE) lab. They’re using undifferentiated stem cells to build functioning patches of heart tissue that can directly replace damaged or malfunctioning heart-muscle cells (cardiomyocytes).

The work offers a different approach than injecting stem cells into hearts, which is another experimental technique to achieve the same goal.

Bursac notes that injected cells frequently can’t be placed in the optimal location, and they often don’t survive or function correctly. A patch, however, can place the needed tissue in the best location, optimizing the likelihood of cell integration and survival.

“It helps to go in with a defined tissue structure,” Bursac says. “So while implanting a cardiac patch is more invasive surgically than injecting cells into the heart, it will hopefully be more functional.”

The federally funded CETE lab -- a component of the Pratt School of Engineering’s Biomedical Engineering program -- is investigating the structural and functional interactions among implanted heart muscle cells and other cells.

“We’re trying to see how well these cells connect with the myocardium and contract with the rest of the heart,” Bursac says. The goal is for these cells to integrate well enough with existing heart tissue that they will be electrically and mechanically in sync -- contracting and conducting signals as if they were part of the heart.

A recent study of experimental patches using embryonic stem cells from mice -- now submitted for publication -- shows the current models to be “working beautifully,” Bursac says.

Duke cardiologists Howard Rockman, MD, and Lan Mao, MD, who implant the patches in mice and rats in Rockman’s laboratory, believe the patches have the potential to be of great benefit to people with cardiac damage and disease.

Balloon Sinuplasty: Cutting-Edge Sinus Surgery with No Cutting Involved

Wed, 22 Jun 2011 10:33:02 -0400

The lights are turned down low in the balloon sinuplasty room at Duke Otolaryngology of Durham. Relaxing music plays softly. A 63-year-old woman with a lifelong history of painful chronic sinusitis lies back in a reclining chair.

Otolaryngologist Donna Sharpe, MD, inserts a flexible catheter into her patient’s right nostril. Using the endoscopic image on a nearby video monitor, along with a previous CT scan of the patient’s sinuses, Sharpe carefully guides the tiny catheter into the inflamed and mucus-filled frontal sinus.

She follows that with a lighted guide wire that illuminates the hollow cavity. The patient’s forehead glows like a firefly, confirming that Sharpe has reached her target.

The physician inserts a small balloon, similar to those used for cardiac angioplasty, along the wire inside the catheter. Once the balloon is properly positioned in the blocked ostium, Sharpe inflates it, dilating the sinus opening.

As she removes the deflated balloon, the sinus drains. The patient feels a decrease in pain and pressure, and the procedure is over.

In many cases, that’s it.

As needed, Sharpe will irrigate the sinus to flush out stubborn mucus or other material, but often, the relief is immediate. The patient is pain-free, breathing well, and ready for normal activity right away. No incision, no mechanical debriding of tissue or bone, little or no bleeding, and a patency rate exceeding 90 percent.

“It’s a pretty awesome technology,” Sharpe says.

Despite its success rate, outpatient balloon sinuplasty is not for all chronic sinusitis sufferers. Patients must possess the anatomy to allow access via the catheter (blockages such as a deviated septum or sinus polyps are disqualifiers), and need the temperament to tolerate surgical work inside their head under local anesthesia.

In May, Sharpe became the first physician in North Carolina to perform balloon sinuplasty in an office setting. She performed it for three years in an operating room on patients under general anesthesia, which is still an option for patients who are otherwise qualified for the procedure, but are too anxious to sit still for it.

During that time, she spoke often to colleagues about the possibility of doing the procedure on an outpatient basis. Recently, technology caught up with the ambition of Sharpe and other like-minded otolaryngologists, allowing the technique to be comfortable and easily used in an office.

Balloon sinuplasty follows the trend of other surgeries that have become more accessible once they became less invasive. Approved by the Food and Drug Administration as well as the Centers for Medicare & Medicaid Services, the procedure costs about one-tenth as much as an office procedure as it does in an operating room.

And patients such as Sharpe’s lifelong sinusitis sufferer leave her office ready to return to their day -- sinus-pain free, says Sharpe. ”That patient went home and cleaned her house, and she entertained guests that night.”

Sharpe performs outpatient balloon sinuplasty at her office, Duke Otolaryngology of Durham; she performs the inpatient procedure at the James E. Davis Ambulatory Surgical Center and at Durham Regional Hospital. To learn more or make an appointment, call 919-220-2020.

Rebuilding Smiles: Updates in Cleft Lip and Palate Repair

Wed, 22 Jun 2011 10:16:46 -0400

Jeffrey R. Marcus, MD, director of the Duke Cleft and Craniofacial Program, says that in treatment of cleft lip and palate, less really is more.

Jeffrey R. Marcus, MD

In decades past it was not unusual for a child with a cleft lip and palate to undergo 10 or more procedures before age 12. “Our primary goal will always be to achieve the very best result possible,” he says. “However, it is no longer necessary or reasonable to have a child go through so many steps.”

For procedures that are necessary, the Duke cleft team creates a clinical plan for each child according to the most up-to-date protocols. Less surgery means less recovery time, less exposure to anesthesia, and fewer related risks.

“We strive with every patient to consolidate and coordinate procedures and to avoid the need for revisions,” Marcus says. “Revisions are almost never as good as a perfect first surgery, so when we do anything, we do it to last a lifetime.”

Over the past eight years, the Duke cleft team has not had to revise a cleft palate repair, and only rarely must revise a cleft lip repair.

Innovative Technique Improves Outcomes

Since the program began offering an innovative presurgical orthopaedic therapy, outcomes are better than ever. The process -- called nasoalveolar molding, or NAM -- greatly facilitates the primary lip, palate, and nose repair many cleft patients undergo.

Craniofacial orthodontist Pedro E. Santiago, DMD, helped develop the technique in the mid-1990s and brought it Duke two years ago, making Duke’s program one of few in the United States to offer NAM and the Southeast’s most experienced NAM program.

When NAM is appropriate and desired by a family, Santiago’s team sees infants at about a week old. He evaluates the cleft and makes an impression of the baby’s upper jaw, a three-minute procedure that doesn’t require anesthesia. The impression is used to make an acrylic molding plate -- similar to an orthodontic retainer -- that is inserted and then adjusted weekly for three to four months to narrow the cleft.

Unlike other presurgical orthopaedic techniques, NAM brings the nose up and lengthens the skin between the nostrils, laying the groundwork for optimal outcomes when surgeons perform the primary nose and lip surgeries. “Lip repair alone cannot solve the stigma of the cleft nasal deformity,” says Santiago.

“Once the lip and bony segments are close together, we add a nasal extension to the plate to mold the deformed nasal cartilages,” he explains. “This improves nasolabial symmetry and balance, and is critical to facial aesthetics.”

It takes few days for families to get used to the plate, but “by week two, mom and dad are experts at managing it,” Santiago says. “Babies aren’t crazy about it at first, but it doesn’t hurt them, they get used to it, and it’s pretty easy to spot problems. If a particularly bothersome issue should arise, parents can always take the plate out while we make adjustments.”

Some children with clefts aren’t candidates for NAM -- but their outcomes are also good, says Marcus. Regardless of a child’s age or condition, “Duke offers options for every scenario,” adds Santiago. “We like to meet the child, meet the family, and discuss their unique situation, goals for treatment, and resources, so that we can develop a comprehensive and realistic plan of action that’s appropriate for that family.”

Consistency of Care Benefits Patients

As children grow up, they continue to see their same surgical team for monitoring, an important practice that provides long-term consistency of care as patient needs evolve.

“We stick with our patients throughout their lives, and those relationships really grow,” Marcus says. “Of all the things I do in medicine, caring for kids with clefts is probably the most rewarding. There is no greater sense of meaning than to look at a child with a cleft and to know that you have an opportunity to help him or her be like other children.”

Santiago agrees. “It makes my life more meaningful to be able to get to know these patients and families, and make such an important impact on their lives.”

Mighty Metabolites: Metabolomics Research Is on the Fast Track

Wed, 22 Jun 2011 11:09:26 -0400

Two men walk into their doctor’s waiting room, and with them arrives the puzzle that plagues so many physicians.

The men are of similar build, age, and ethnic background. They have the same general diet and lifestyle habits. However, in two years, one of these men will die of a heart attack. The other will live for many years with no heart disease.

Chris Newgard, PhD, and Svati Shah, MD

How does the doctor know which man is at immediate risk?

Two of our most intractable diseases -- heart disease and diabetes -- are widely accepted as having a “multifactorial” origin in most patients.

They can’t be explained by genetics alone, and the mishmash of contributing behavioral causes are not only maddeningly variable from patient to patient but also nearly impossible to measure accurately over the decades it takes for their impact to play out.

So far, the best laboratory tests still cannot identify with any reliability just who will get sick from these illnesses and who won’t.

But what if they could?

This is the goal of metabolomics: a relatively new field of studying the chemicals produced by the many metabolic processes in the body. “Your body is in a constant state of metabolism,” explains Duke cardiologist Svati Shah, MD.

“These are the processes that help regulate the sugars, protein, and fat that you eat, and the conversion of these fuels to energy.” The goal of metabolomics is to try to measure the byproducts of these processes and use those measurements as biomarkers for the health -- or illness -- of the body.

Metabolomics serves as the integrated readout for the other “-omics” sciences, such as genomics or proteomics, says Duke researcher Chris Newgard, PhD. “Genomics and proteomics have been big areas of research,” he says.

“But the metabolites are at the end of the funnel: mRNA is the product of the genes, the protein is the product of the mRNA, and the metabolic signature is the integrated readout of how all the individual genomic and proteomic variations affect a person’s physiology. So to me it is the most precise measurement of the phenotype of the individual.”

He skips a beat and says, “Of course, I’m biased.”

But the results of studies published in the last two years have so far backed his claims with hard data, showing that certain clusters of metabolites may be specific and reliable indicators of heart disease and impending diabetes at the individual level.

In fact, their levels in the bloodstream may even predict which heart disease patients will soon have a heart attack.

Gizmos and Numbers

Measuring metabolites is hard to do, scientifically speaking. They are tiny and exist in the bloodstream in very low concentrations -- micromolar and nanomolar amounts. There are also lots of them -- an estimated 6,500 discrete metabolites in humans. And when you’re measuring anything in the blood, it’s like trying to categorize multicolored sand.

“Your blood is full of the coffee that you drank this morning, the cheeseburger you ate last night, the medicine you take,” says Shah. “So trying to isolate these metabolites among all the other molecules in the blood is a little like being in Times Square and trying to pick out one person.”

The techniques used to measure metabolites have taken years to develop. Newgard, who directs the Sarah W. Stedman Nutrition and Metabolism Center, came to Duke in 2002, after 15 years of working with metabolic technology at University of Texas Southwestern in Dallas.

Once at Duke he worked with David Millington, PhD, and Robert Stevens, PhD, both specialists in inborn errors of metabolism, and other key members of the Stedman Center team, including James Bain, PhD, Brett Wenner, PhD, Michael Muehlbauer, MD, PhD, and Olga Ilkayeva, PhD, to build what is today one of the world’s most sophisticated metabolic labs.

The Stedman laboratory collaborates with researchers from all over the world (including colleagues at Duke-NUS), who know the group for providing a level of data specificity that is not available in most labs.

Metabolomics researchers use mass spectrometry to identify and measure a wide array of small-molecule metabolites. “A lot of labs will do a mass spec analysis and get a pattern that shows metabolite levels, then compare the patterns among a group of patients,” Shah says.

But the Stedman lab goes further, adding standards to provide a truly quantitative measure of a sample’s components. So instead of patterns, what comes out of the Stedman lab are numbers -- measurements of metabolites in their exact amounts.

“The Stedman lab can tell you what’s in your blood, and exactly how much of it there is,” says Shah.

“Many metabolomics labs are built by either instrument jockeys or statisticians,” says Newgard. “We take the perspective of the biochemist, the molecular biologist, and the physiologist. To me it’s important to know what I’m measuring and in what concentrations. Our lab has been built so that we can say here’s exactly what’s in the sample -- so that we can also eventually say this is the significance of it, and this is what it portends.”

Small Molecules, Big Predictions

The data generated by the Stedman lab are beginning to paint very clear profiles of certain high-risk metabolic biomarkers for both heart disease and diabetes.

Part of the group’s success involves a home-field advantage: Duke’s CATHGEN biorepository, which holds health records and blood samples from nearly 10,000 patients who have come to Duke over the past eight years for heart catheterization.

This wealth of samples allowed Newgard and Shah to develop a first-of-its-kind investigation, which showed that the levels of certain clusters of metabolites could predict imminent cardiovascular events, including heart attack and even death.

Through a series of studies, the team has shown that metabolic profiles are heritable -- more heritable than other indicators of heart disease such as BMI, cholesterol, and C-reactive protein.

They compared the profiles of 174 patients who were diagnosed with heart disease and went on to have a cardiac event in the next two years with 174 other heart disease patients who were as closely matched as possible in terms of physical and demographic history, but who had no events over a 10-year period.

Among those groups, a specific metabolite cluster was elevated among patients who had heart events. Then they looked at a group of 2,000 patients who came to Duke for concerns about heart disease, and who have been followed every year regardless of diagnosis.

“We did analysis on the full 2,000, and the exact same metabolites were present in people who had heart events,” says Shah. “I was totally dumbfounded. I really didn’t think it would validate.”

“There was some element of gamble,” says Newgard. “It was a sort of dream, that we would set this toolbox up and it would reveal metabolic patterns that hadn’t been characterized and that were so telling. We couldn’t know whether the methods would be precise enough, or whether we’d be swamped out by human variance -- mood, behavior, all the things that go into being human, would those things make it impossible to see the chemistry of disease?”

But cardiologist William Kraus, MD, a co-investigator on these trials and a co-founder of CATHGEN, says that the experiments were hardly a shot in the dark. “We specifically selected clusters of metabolites that we know are involved in multiple pathways of lipid, protein, and glucose metabolism -- pathways that are often disrupted in heart disease -- and we found that they are indeed associated with heart disease and subsequent risk of cardiac events,” Kraus says.

“These metabolic profiles may be a long way from routine clinical use, but we feel they are a good first step in that direction.”

Making Sense of Signatures

Newgard and Laura Svetkey, MD, director of clinical research at the Stedman Center, had previously identified a different discrete cluster of metabolites, dominated by the branched-chain amino acids (BCAA), as a player in insulin resistance.

“The data have shown very clearly that the higher the level of this factor, the higher the level of insulin resistance in the patient -- even after adjusting for factors including weight,” says Svetkey.

When the team looked at whether insulin resistance improved with weight loss, she says, it showed that the higher the BCAA factor in a patient, the more that patient’s insulin resistance improved with weight loss -- again, even after adjusting for weight.

Kraus says a forthcoming study shows that metabolites can help predict who will most benefit from exercise training, in terms of reducing insulin resistance.

The factors controlling levels of these metabolites in the body are downright mysterious: a recent study that Svetkey, Shah, and Newgard participated in showed that the levels of this cluster dropped significantly after gastric bypass surgery -- more so than after weight loss induced by dietary intervention.

“We don’t know some very fundamental things that will help us interpret our results,” Svetkey says. “For example, BCAA comes from meat, and we don’t know how meat consumption or the duration of fasting before we do the blood tests will affect the metabolomics profiling results. We also still need to understand the extent to which this factor differs by age, sex, race, and so forth. Some of these questions can be addressed with the data we already have, and some will require new research.”

And finding a reliable pattern isn’t enough, says Newgard. “When we see those signatures, we want to understand what they do mechanistically. What does this mean at the level of the cells, at the level of the pathways, and can we do anything to change these patterns,” he says. Newgard is continuing research in animal models to see how changing the diets of rats may affect their levels of BCAA metabolites -- and also their clinical outcomes.

Shah is working to identify the genetic makeup that may put people at risk for the metabolomic profiles that presage insulin resistance, type 2 diabetes, and cardiovascular disease.

“The ultimate utility of this kind of investigation remains to be seen,” says Svetkey. An analogy, she says, is the genomics revolution: while genetic discoveries may have had significant and direct impact on several diseases, none have yet made a dent in any of the major public health problems of our day -- hypertension, obesity, heart disease, diabetes.

“Chris would argue, and I’d agree, that metabolomics approach is more likely than the other ‘omics’ to lead to clinical impact. Because while genes are static, metabolites are mutable -- they can be altered by drugs, by behaviors. It’s something we may be able to affect, to use to help our patients.”

From the Brink: Ventricular Assist Devices for Heart Failure

Fri, 21 Jan 2011 12:52:07 -0500

Sometimes it pays to be a zebrafish. You could stab a zebrafish in the heart, and that zebrafish would grow new heart muscle and keep on swimming.

This is not true of the human heart.

The human heart can take many an insult, that much is true. But after a heart lives long enough or suffers greatly enough, it will begin to give out. In fact, this is a guarantee for us all: if something else doesn’t get us first, eventually our hearts will fail.

Heart failure isn’t really a disease. It’s a syndrome -- a collection of symptoms that comprise the bottom of the great funnel of heart diseases, disorders, and distresses. Whether you get there as a side effect of cancer treatment, a devastating heart attack, an unlucky viral infection, or decades of high blood pressure or atherosclerosis, it is the state of being in which the heart simply doesn’t pump as strongly or effectively as the body needs it to.

Its symptoms stem from the body’s attempts to compensate for its failing pump -- the kidneys sense a reduced blood volume and compensate by retaining fluid, which begins to seep out into the body’s tissues and organs, causing swelling, lung congestion, and so on. Without the pump at its prime, the body starts to sputter, to stall out.

Between the body’s dogged insistence on survival and the advent of medical management breakthroughs such as ACE inhibitors and beta-blockers, many people who develop heart failure today can expect to live for years, perhaps with symptoms but also still very much able to work, travel, spend time with family and friends, even exercise. But heart doctors will tell you that once the condition reaches an advanced stage, heart failure patients are difficult to treat, and their quality of life is very poor.

“Surgical treatments for heart failure deal with the sickest of the sick,” says Carmelo Milano, MD, a cardiothoracic surgeon who specializes in care of heart failure patients at Duke.

“When you talk about medical management of heart failure, many of those patients still have some mobility, they can still walk across the room. The patients we evaluate for advanced surgical options have symptoms of heart failure even when they’re at rest.”

They can’t sleep, eat, bathe, or even enjoy the comfort of a loved one’s touch without the constant companion of half-drowned breathing, fatigue, and pain. They are moribund; they are out of options.

Unless, of course, they can be brought back from the brink. Advanced heart failure has one well-established treatment, and that is transplant. The success rate of heart transplant is booming today, boasting nearly 87 percent one-year survival nationwide (at Duke it’s 88.7) and 54 percent 10-year survival (59 percent at Duke).

For the transplant team, Milano says, the gig can really mess with your personal life -- “It’s emergency surgery, so we’re often operating in the middle of the night. But the difference it makes in our patients’ lives, within just a month or two of the surgery -- it’s incredible. That’s what keeps drawing me to it.”

Every transplant surgery is an opportunity to recycle tragedy into triumph -- death makes possible life. But the trouble with transplant is just that: it depends on the unplannable, unexpected, and terrible loss of life.

And it’s not even as simple as that -- to be brought back from the dead, both the donor heart and the recipient must meet very stringent criteria. There are at least 150,000 people in the United States currently on waiting lists for heart transplants, but this year there will be only about 2,200 heart transplants performed.

In 2000, Duke created an extended criteria transplant program, which has given 70 hearts to patients who would otherwise not have been candidates and made use of donor hearts that would otherwise have not been transplantable. But even with the success of that program, patients and physicians are still confronted with a supply dependent on loss and woefully undermeeting demand.

“Transplant is a wonderful therapy,” says Duke cardiologist Joseph Rogers, MD, who works with Milano to care for patients with advanced heart failure. “But in the world I live in, there’s this huge clinical need, and there’s just not enough organs to help all of our patients. So the question becomes, what do you do to help the rest of these people?”

Learning to Fly

Former vice president Dick Cheney has a troubled heart, to be sure. At age 69, he’s already survived five heart attacks and undergone quadruple bypass, two angioplasties, and placement of an implantable cardiac defibrillator (ICD).

This summer, to treat his advancing congestive heart failure, he was implanted with one of the newest generation of VADs, or ventricular assist devices.

VADs are the current answer to the question of a viable artificial heart -- basically, they replace the heart’s left ventricle, which is its main pumping chamber. The device attaches to the heart, and its battery-powered pump (controlled by a small, externally worn computer) pulls blood from the left ventricle and sends it through the aorta.

It’s not clear whether or not Cheney ultimately will receive a transplant, but the choice to use a VAD to treat such a public figure may mark the turning point in public opinion on this type of technology.

Such heart pumps were originally approved by the FDA only for use as a medical stopgap, to keep a patient alive while he or she awaited a heart transplant. But recent studies at Duke and other institutions are showing that more and more patients are living with a VAD indefinitely -- and they are living well.

In his sixteenth-century Codex on the Flight of Birds, da Vinci declared that “a bird is an instrument working according to a mathematical law, which instrument it is within the capacity of man to reproduce with all its movements.” Milano uses that quote to remind himself of the possibilities that are in our grasp, such as a man-made replacement for a broken heart.

But Milano will be the first to say it -- a plane is not a bird. And when it comes to building a device that can replicate the human heart’s 100,000 daily pulses that circulate six liters of blood through thousands of kilometers of blood vessels, man’s now-conquered quest to fly seems rather like child’s play.

It’s hard -- maybe harder for the doctors than the patients -- to shake the memories of earlier “mechanical heart” devices. The well-publicized deaths of some patients in the late 1980s who were implanted with the Jarvik Seven -- an artificial heart that was powered by refrigerator-sized air compressors -- led that device to be dubbed in an often-cited New York Times op-ed as the “Dracula of medical technology.” Those patients suffered postsurgical infections, sepsis, delirium, and organ failure.

But by 1994 a new model of heart device -- the VAD -- was progressing through clinical trials. Instead of completely replacing the heart, these ventricular assists bolster the heart’s function by taking on the lion’s share of the pumping process.

These first models were in fact pulsatile -- they mimicked the pulsing action of the heart. The devices were exciting, but “everybody thought we wouldn’t be able to get these people out of the hospital,” says Laura Blue, NP, nurse coordinator for the Duke VAD program. “We had to push really hard and be very cautious. It took years to develop safe ways to discharge patients.” Through the late 1990s, Duke took part in several national trials to test the devices.

In November 2001, results of REMATCH, a national trial to compare VADs to medical management in patients who weren’t transplant candidates, were published in the New England Journal of Medicine (NEJM).

Positive outcomes in VAD patients helped garner the approval of the FDA first for use in patients who needed to buy more time while they waited on a transplant list, and then as the destination therapy itself.

In July 2003, Duke performed North Carolina’s first destination therapy VAD implant.

“We were the first hospital in our region who ever sent a VAD patient out in the community,” says Blue. “It was entirely new type of life support; so at first, for every patient we implanted, I went to their local EMS station and met with the chief and the training officer, so that they’d know what to do if the patient needed emergency care.”

According to just about everyone who worked on them, the VADs were “like breathing life back into dying people,” says Blue. “I always loved transplant medicine, but the VADs really felt like, wow, we were stopping the train headed off the cliff. While it was not easy, they were alive, they were going to make it.”

Refining the Flow

Though Duke patients overall had outcomes that exceeded even the REMATCH standards, as a widespread practice VADs were still problematic. The pulsatile models were “bulky, noisy devices that had lots of moving parts that would break frequently,” says Rogers.

It was to be counted on that, within a year or 18 months, something in the pumps would break, requiring another operation to replace the pump. A Duke study published in November 2008 in JAMA showed that, among Medicare patients who received these pumps between 2001 and 2006, the one-year mortality was still high -- 45 percent -- as was cost.

“We learned several things from that study,” says its lead author, cardiologist Adrian Hernandez, MD, who like Rogers cares for VAD and transplant patients at Duke. He says the data showed that, like other highly complex technical treatments, one of the most important factors in determining outcome was the experience of the team who performed the procedure.

Hospitals with smaller procedure volume trended toward poorer outcomes than hospitals with more frequent procedures. And when you’re dealing with an $80,000-per-person technology, as Hernandez says, “we really want -- and really need -- to be responsible citizens with this.”

By 2008, though, design of the pumps had taken a new leap: a new generation of continuous-flow pumps, such as the HeartMate II, had abandoned the notion of pumping like a heart in favor of a tube-shaped axial flow pump, which boasted only one moving part and was one-seventh the size of its pulsatile predecessor.

Rogers and Milano helped lead the study to test this new model, and the results -- presented and published in the NEJM in November 2009 -- showed that after one year, 68 percent of patients on the continuous flow VAD survived, compared to 55 percent in the pulsatile flow group.

Following the second year, 58 percent survived (compared to 24 percent with the older device).

“And there was a 38 percent reduction in patients who needed to be re-hospitalized in the continuous-flow group,” says Hernandez, noting that heart failure is the number-one contributor to the country’s rates of hospital readmissions.

These reduced re-hospitalizations were attributed to significantly fewer major adverse events, including infection, difficulty breathing, kidney failure, and cardiac arrhythmias.

Outside the hospital, the HeartMate II patients were thriving. Heart researchers will often reference the “meters walked in six minutes” as a metric of the effectiveness of a new intervention in heart failure. Rogers explains that this measure is particularly important, because it represents the difference between a person who can go to the grocery store, go to church, go to his family reunion, and the person who cannot.

“Our patients don’t exercise on treadmills every day,” says Rogers. “But we want them to be comfortable doing what they like to do—going out to eat, shopping, golfing.”

According to the Duke research, compared to people living with heart failure, the improvement in these kinds of quality-of-life scores go up dramatically within three months of implanting a HeartMate II pump, and they stay high for at least two years (the longest period of time studied so far). “The improvement in this measurement went up more than any other therapy we’ve tested in non-transplant advanced heart failure patients,” says Rogers.

Duke cardiologist Michael Felker, MD, who is also on the transplant and VAD team, adds that there are few things in medicine that you can call a magic bullet, but this kind of change in patient quality of life qualifies.

“You can almost think of the VAD like you think of the iPhone,” he says. “Every generation gets a little better.”

Making the Choice

On paper, the benefits of being on a pump seem myriad -- until you remember that the patient has a driveline coming out of her abdomen. The pump sits in the chest, and a small tube connects it to the computer, which is worn holster-style around the patient’s hips.

“It’s not forgettable therapy -- you have batteries, you have a computer, and you have to wrap your head around the notion that you will run on batteries from now on,” says Blue. “I’ve had patients say, ‘Thank you for telling me about this, but it’s not for me.’ And that is the right choice for some people -- I will be the first one to tell anybody that living with a VAD is not going to be easy.”

Blue says that, when the VAD team talks with a heart failure patient about the possibility of placing a VAD, they must take the whole patient into perspective.

“We put these pumps into people who have family to help care for them and a place to go when they leave the hospital. We don’t recommend to anyone that they plan to live alone, at least not at first. We use a caregiver contract, we train them,” she says. “And in some ways it’s harder in younger people, for dual-career households, because early after surgery we ask someone to be with the patient all the time.”

New batteries that weigh less and hold a longer charge have helped ease some of the logistical burdens, and patients leave the hospital with extra batteries and an extra controller. But still, says Blue, it’s an adjustment.

“I’ve run out to the front of Duke Hospital and stood in the middle of Erwin Road, because a patient who came in for her first clinic visit after surgery left her batteries hanging on the back of her wheelchair in the parking garage. Her alarm started going off halfway back to Rocky Mount . . . so there she was, barreling down Fulton Street, and they whipped around the hospital driveway and I was jumping into the car to change out the batteries.”

To some VAD patients, Blue says, the grass looks greener on the transplant side of the fence. “Other than when they take their handful of pills every day, transplant patients can almost pretend that they have a normal life -- they don’t necessarily have to be confronted with their illness every day. And transplant is still the gold standard -- so when we can transplant a patient, we do."

"But transplant patients who have problems, who are sick or have rejection episodes, they can struggle just as much. And they don’t get to give their transplants back. So it’s a decision that we make very carefully. When the VAD patients get past the recovery from their surgery, and they are up and walking, and having a normal life . . . They can’t believe it, how much better they feel.”

Could VAD Outdo Transplant?

The successful outcomes of the new VADs are raising a lot of questions -- and a lot of expectations.

A Duke study found that outcomes in VAD patients and Duke’s extended-criteria transplant patients are the same after two years, and physicians like Rogers and Milano are exploring the idea of placing the devices in patients who are less advanced in the disease process.

This idea is encouraged by outcomes from the HeartWare device, an even smaller, newer VAD design. Investigators at the November 2010 American Heart Association meeting in Chicago reported one-year survival that was greater than 90 percent for patients who received a HeartWare VAD.

“We’re also collaborating with industry partners to evaluate new, experimental devices,” says Rogers. “We’re looking at partial-support devices -- some of those are the size of a AA battery, and they sit in a pacemaker-like pocket in the chest.”

Such devices may supply two or three liters of blood, which is less than the six or seven liters that current pumps flow. But they could be put in with less morbidity, less invasive procedures, and allow these patients to feel better and to function better.

Rogers says that the possibilities give a new optimism to the care of these patients who were once at death’s door.

“There aren’t many chances in medicine to do this,” says Rogers, “where you can take a technology that has such profound effects on patients and how they feel, and actually help it advance.”

“There’s clearly a point when heart failure progresses, when the physician has done the best that can be done with medications, when the VAD option should be considered,” says Blue. “It isn’t for everybody, but for those who say ‘Look, I’ve got grandchildren to raise,’ or ‘I just retired, I was looking forward to a great life -- I want more years’ -- the VAD can give it to them."

“I’ve got an 83-year-old patient who was 80 when we did his surgery, and he’s still going. And the only thing that limits his golf game is his wife.”

Care Beyond Cure: The Rise of Palliative Medicine

Fri, 21 Jan 2011 13:51:01 -0500

My husband’s maternal grandparents died in close succession, and the common belief among family members is that Louie had not cared to linger on after Fanny was gone. Both were in their 70s, and while perhaps not in perfect health, both led active lives, their home ablaze with grandchildren, up to the end.

Fanny’s only obvious concession to mortality her final day was to forego a luncheon she’d been planning to attend. A few months later, Louie was found in his bed, fully dressed, a broom propped nearby, suggesting he had been sweeping the floor, gotten fatigued, and lain down.

Contrasted with the multiple hospitalizations and at-times agonizing decline of my own grandparents, the swift and gentle nature of Fanny’s and Louie’s deaths seems not only enviable but remarkably rare. Barring sudden death by violence or accident, most of us face lengthy, medicalized journeys toward the end of life.

Constantly advancing technologies offer hope against disease and debility, though often at the cost of clarity on when and how to throttle back when there’s always one more round of chemo, one more clinical trial, and an array of machines and medicines to sustain basic functions.

“Hope is not a plan, but hope is our plan,” observes surgeon Atul Gawande in his unvarnished assessment of end-of-life care recently published in The New Yorker. If saving lives is the primary function of health care providers, then what is their role when cure is no longer the goal -- or at least not the only goal?

“Just to keep treating is no longer an acceptable default,” says Tony Galanos, MD, medical director of the palliative care service at Duke University Hospital. “We can keep practically anyone alive. The real question is, what kind of life do you want to live?”

Palliative medicine represents a different model of care, focusing not on cure at any cost but on relief and prevention of suffering. Here the priority is supporting the best possible quality of life for the patient and family, regardless of prognosis. Ideally, the principles of palliative care can be applied as far upstream as diagnosis, in tandem with cure-directed treatment, although it’s still associated in most people’s minds with end-of-life care.

For that reason, it may at first glance seem almost incongruous that palliative medicine is being advanced at an academic medical center like Duke, where people tend to come seeking miracles.

“People think that palliative medicine means you’re giving up, or that it’s basically hand-holding and low-tech,” says Galanos. “But it is aggressive medicine. I consider it acute care -- figuring out what bothers the patient the most, whether it is nausea, pain, confusion, or delirium, and treating that thing aggressively."

"We should never say, ‘There is nothing more we can do for you’; that comes from a curative-only point of view and abandons the patient. There is always something to do in the service of making someone feel better.”

The concept of palliative care has been gaining momentum throughout the Duke system in recent years via a robust research program, education of medical and nursing students as well as house staff, and increased inpatient services.

Duke University Hospital president Kevin Sowers, RN, MSN, says it’s vital to providing the full spectrum of care: “While we offer hope and even cure in many types of diseases, we also need to better understand the art and science of caring for people at all stages of life, including the end of life. Along disease trajectories, we need to be prepared for everything from delivering the most aggressive treatments to concentrating on managing pain at the end of life.”

There is an economic incentive for hospitals to support palliative care -- research shows significant reductions in pharmacy, laboratory, and intensive care costs -- though there’s understandable reluctance to tout such benefits. After all, accusations of “death panels” effectively shut out government funding for palliative care as national debates about health care reform took shape last year.

James Tulsky, MD, director of the Duke Center for Palliative Care, which encompasses teaching and research as well as clinical care (such as Galanos’s consult team), says that the medical community needs to push back against the death panel smears. While palliative care may save money, money is not the motivation of the care provider.

“We don’t walk into the room thinking we’re going to save the hospital money,” he says. “If we do our job right, we do save money, but the overwhelming majority of the time, what we hear from patients is how we made things better.”

In fact, new research recently appearing in the New England Journal of Medicine suggests palliative care may actually prolong life -- and a higher quality of life at that. Patients with terminal lung cancer who received palliative care upon diagnosis reported greater mobility and less pain and depression than their counterparts who did not. And, somewhat ironically, they lived close to three months longer.

Bringing Up the Subject -- Sooner

Research suggests that doctors tend to be overly optimistic in their prognoses, offering inaccurate longer survival prospects. Pile on the difficulty of initiating conversations that acknowledge the possibility of death, and the result is that too many care providers delay addressing changing care goals and pursuing palliative measures until very late in the game, if at all.

The average length of patient involvement in a hospice program, for example, is a mere two to three weeks, though studies suggest that a minimum of three to six months is needed to truly benefit.

Palliative care does not necessarily mean hospice, though hospice is a subset of palliative care. “Palliative care describes the broad field of care for patients with serious illness,” Tulsky clarifies, “while hospice is a system of care appropriate for patients with life-limiting terminal illness, defined by Medicare as lasting six months or less.”

That explicit acknowledgment of death, abetted by misperceptions surrounding what hospice care entails, can be off-putting to patients and physicians alike, says Toni Cutson, MD, physician leader of the palliative care consult team at the Durham Veterans Affairs Medical Center and medical director of Duke HomeCare & Hospice.

“A patient I talked to recently said, ‘Oh no!’ fearing we’d automatically take away all her medications and put her on morphine. Even doctors think that hospice means that no IV fluids or antibiotics are administered, but we’re often caring for patients with complex problems, and offering comfort may mean giving IV fluids, transfusions, or antibiotics in situations where we think it’s going to help.”

In fact, as Duke hospice patient Connie Kerr can attest, effective symptom management can mean significant gains in mobility and function, even as a patient’s disease continues to progress.

A year ago, Kerr was feeling overwhelmed by her advancing chronic obstructive pulmonary disease (COPD). “I was so tired, and it was so much trouble keeping up. Breathing was getting harder and harder,” she says -- so much so that it came almost as a relief when her physician, Duke geriatrician Heidi White, MD, broached hospice care.

“Physically, mentally, she’d had enough,” agrees Charlie, her husband of 51 years.

Today the mood is upbeat in the Kerr household. Connie, though reliant on a wheelchair from a recent fall and tethered to her oxygen pump, is lively, with a radiant smile. “Everybody in the family has the feeling that I’ve lived much longer from having gotten involved in hospice,” says Connie. “Maybe it’s from relaxing the stress or just knowing the nurse will be here once a week.”

“She’s like family,” Charlie says of Donna Ratliff-Walker, the primary nurse from Duke HomeCare & Hospice who oversees Connie’s care through weekly visits. “We generally laugh most of the time she’s here.”

Certain changes in Connie’s medications, made in accordance with the shift in her care priorities toward symptom management, have brought immense relief. Prednisone, for example, was something her pulmonary team had been reluctant to prescribe. “They didn’t want me to get on it because they said I’d have to stay on it,” recalls Connie. “But the minute I got a little bit of prednisone, I had a lot more energy and appetite for interesting food -- and these things help tremendously!”

Also helpful has been Connie’s “moondrops” -- the couple’s playful name for the morphine that eases the tightness in her chest so that breathing need not feel like such an epic struggle all the time.

With Connie in less distress from her symptoms, the Kerrs are able to focus on enjoying their time together. “There are so many positive things about it,” says Charlie. “We’ve always been close. There are so many things we’re both interested in. You read and share with me -- and I’m a pretty good masseur.”

“We would like to go on with our life as much as possible the way we have,” says Connie. “I want to still be able to laugh, and to see and talk to people.”

Her recent fall, which might easily have proved calamitous for an 83-year-old woman with advanced lung disease, seems more like a temporary setback. “I should be working more on using the walker instead of the chair,” she confesses. “I broke my right wrist when I broke my hip. I’ve never used my left hand; I sort of had to start from scratch.”

“You’ve taken all these things in stride just remarkably,” Charlie says to his wife with admiration. “My heavens, here you are eating with your left hand. You could say the hell with it, but you don’t.”

Agenda: No Agenda

An important function of palliative medicine is helping people define their goals -- for their care, and for the days they have left. “People are struggling with figuring out the right goals and putting them into action,” says Tulsky, “particularly when making the shift from treatment directed toward cure to treatment for comfort.”

Duke’s palliative care team, which does around 500 consultations a year and reaches into every unit of the hospital, provides expert navigation through these difficult but very necessary communications.

“We like to say that our ‘procedure’ is the family conference,” says Tulsky. “We walk into a room with no agenda; we assess without an agenda. We’re curious: we want to learn who they are, their goals, their values -- then with those things in mind, help them determine whether it’s appropriate to make a shift in the course of treatment.”

“We’re not there to convince people they should or shouldn’t be DNR,” says Galanos. “We are there to help them feel better in whatever ways they need. Our consults are labor- and time-intensive to ensure their preferences are honored.”

Nurse practitioner and palliative care coordinator Jennifer Gentry is often the first person on the team to meet the patient. “The majority of our consults are because of communication issues,” she observes. “The patient may be very ill, things are not going well, and there’s a disconnect between what the care team thinks and what the patient and family think.”

Talking to patients and families takes sensitivity and skill. “The biggest mistake is to talk too much,” says Gentry. “Start with open-ended questions: ‘How are things going?’ ‘What do you understand about the illness and treatment?’ Then be quiet and listen.”

Conflict among family members is also common, especially when there’s disagreement about what should be done for a patient who may not be able to clearly communicate his or her wishes.

“We’re assessing family dynamics the minute we walk in the door,” says Gentry. “Are people sitting together, supporting each other? You can identify very quickly who the decision-makers are, and what the cohesiveness of the family is. When people are quiet, we make an effort to bring them into the conversation. We try to get comments from everyone. Even when there’s no consensus, the one thing we can all agree on is that we all care about the patient. That’s a place to start.”

Part of providing good end-of-life care to patients and families is “helping people resolve unfinished business,” says Cutson. Delaying a turn to palliative measures or hospice care until the very end does the patient a disservice.

“In the final days and hours of life, time is focused on effectively managing symptoms, and there may not be enough time to know all the members on your care team and establish trust. Once you have that and still have some energy, you can focus on those things that are so important.”

Patients may have specific goals to meet. For example, “We worked with a gentleman who wanted to make it to his 60th anniversary, so his short-term care was directed toward that,” Cutson says. “Afterward, he wanted a different approach.”

In the case of a young mother who knew she wouldn’t live to see her children grow up, hospice workers helped her make a treasure box full of meaningful souvenirs and letters for the children to open on birthdays and other special events in their lives.

“Someone has to be very brave to do this,” notes Cutson. Such bravery may not even be conceivable to a patient who is overcome by pain and nausea and can’t get past those immediate needs, or whose care team has not yet invited her to consider what she would want in the event that treatment doesn’t work.

“A person dies once, so we have one chance to get it right,” says Camille Lambe, a nurse practitioner who teaches palliative care in the Duke University School of Nursing. “When it goes well, families are so appreciative. I get notes saying you were there, you talked with me until I had no more questions."

"When it doesn’t go well, families are devastated. They carry it for years. They remember the abrupt doctor that stood at the door and said, ‘You have terminal cancer.’ It colors the way they come to every other experience. We have to come prepared and get it right.”

Filling the Void

Offering comfort beyond the physical, addressing pain that is emotional, spiritual, or even existential -- such tasks reflect a broader view of patient care than our current medical model necessarily supports. But health care providers must deal in these larger issues to truly serve their patients, says Richard Payne, MD, Esther Colliflower Director of the Duke Institute on Care at the End of Life, which resides in the Duke Divinity School but maintains a strong partnership with the medical school.

“Once one gets beyond the challenges of symptom management, most of what concerns patients and families are issues around preparation and closure: How do I talk to my family, my spouse? What’s my legacy? If I’m a person of faith, what does this mean in terms of my relationship to God? They’re all very important questions, and they’re not peripheral to medical care, because if these matters are left unresolved, they are a tremendous source of suffering.”

In some ways, health care providers find themselves in the position of filling a cultural void. “For most of recorded human history, we took care of our loved ones who were near death not in institutions but at home,” notes Payne.

“It was once quite common for young people to have experienced physically the death of a parent or grandparent. Over the last 100 years, we’ve turned dying into a purely medical event that takes place inside hospital walls. People no longer have a sense of what it is to be near those who are dying.”

Part of the institute’s mission is to better equip all those who have that role: “We create training opportunities for doctors, nurses, and clergy to help them attend to all sources of suffering in the patients they encounter. Education in communication is a huge strategy.”

Effective communication skills can be honed through practice, but overall Payne urges the medical community “not to be as reactive and passive as we have been. Patients and families are looking to us to advance the conversations. Too often we only ask patients what they want to do, thinking that’s empowering them, but we need to be facilitators and be much more proactive in walking them through their options, making sure that they understand the risks and benefits.”

Duke pediatric oncologist Ray Barfield, MD, who also serves at the institute, suggests that care providers who want to be more fully present for their patients during their most difficult moments need to broaden their perspective.

“The ways families experience illness is really different from the way we focus on rounds or on our clinical practice. We’re biological, talking about systems, infections, chemo -- all of that’s incredibly important, but families are experiencing it from the inside; it transforms every part of their lives.”

Hospitals host miracles and tragedies on a daily -- if not hourly -- basis, and palliative care may be the one constant in the ever-shifting sands of life-threatening disease. There’s continuity in providing comfort, and a deeply comforting assurance to patients, perhaps best expressed by Barfield: “My primary goal may be to cure your disease, but I can also improve the quality of your day, at whatever stage you are in. Up to the very last day, I care about the quality of your day.”

Clinician Q&A: Fighting Fatty Liver Disease

Fri, 21 Jan 2011 14:52:15 -0500

It’s estimated that almost 80 million Americans have nonalcoholic fatty liver disease (NAFLD), in which fat accumulates in the liver cells (steatosis).

A small fraction of patients progress to a more serious form of the disease, called nonalcoholic steatohepatitis (NASH), in which inflammation and some cell death occurs, and a minority of patients with NASH progress to liver fibrosis (scarring) and even cirrhosis and liver cancer. NASH ranks as one of the major causes of cirrhosis in the United States, behind hepatitis C and alcoholic liver disease.

DukeMed Magazine talked with two Duke clinician-scientists who study the causes of NAFLD and each day translate what they learn to the patients they treat.

Anna Mae Diehl, MD, is chief of the Division of Gastroenterology and a researcher who conducts animal studies of NAFLD as well as human clinical studies.

Manal F. Abdelmalek, MD, is an associate professor of medicine in the Division of Gastroenterology; she’s an epidemiologist and researcher who conducts clinical trials and studies NAFLD from a public health standpoint.

Which patients are at risk for NAFLD?

Abdelmalek: Patients who have obesity, high cholesterol, insulin resistance, and hypertension should be considered at high risk. Because most patients with NAFLD do not have symptoms until the disease is more advanced, periodic evaluation of liver enzymes in patients at high risk should be considered.

Elevated liver enzymes on routine blood tests can be a sign of NASH if there is no other reason for liver disease, such as viral hepatitis or excessive alcohol use. A “bright” liver on abdominal ultrasound might suggest the presence of a fatty liver.

If my patient has NAFLD that has not yet progressed to NASH, when should I consider referring him to another specialist?

Abdelmalek: The most accurate method to differentiate simple fatty liver from NASH is liver biopsy. Therefore, if there is any suspicion of possible fatty liver disease based on the presence of multiple risk factors, features of fatty liver on an imaging study, or unexplained elevation of liver enzymes, patients may be referred to a specialist for further evaluation, counseling, and possibly staging of underlying liver disease.

Although no pharmacologic therapies are approved for the treatment of NASH, antioxidants such as vitamin E, lifestyle and dietary modification, and medications such as pioglitazone or metformin -- medications typically used to treat risk factors which may contribute to disease progression -- may be warranted.

Patients with more advanced forms of NAFLD would require further care and monitoring for potential complications of cirrhosis. At Duke, we individualize treatment depending on the risk factors that patients have which may contribute to disease and its progression. We also provide follow-up when needed, which may be necessary for patients with NASH and/or advanced fibrosis or cirrhosis from NAFLD.

We will also determine those patients who have steatohepatitis [NASH] and who may be considered for treatment studies.

Are there specific dietary interventions that can help?

Abdelmalek: In addition to treatment of risk factors such as high cholesterol and diabetes, we have learned that diet matters.

We have recently reported that increased consumption of fructose is a risk factor for fatty liver, independent of obesity. In that study, patients who had fatty liver disease were more likely to consume high levels of fructose compared to patients of the same age, gender, and body mass index who didn’t have fatty liver disease.

In a different study, published in June 2010 in Hepatology, we found that among patients with fatty liver, those who consumed the most fructose were more likely to have advanced disease. In that study, we evaluated a very large cohort of patients from the NASH Clinical Research Network, and we found that the more fructose that patients with fatty liver disease consumed, the higher their risk of liver inflammation, swollen liver cells (also called ballooned cells), and even fibrosis, despite controlling for other factors that may contribute to those outcomes.

This was a very interesting discovery because up until that study, we hadn’t been able to tell patients what dietary factors may contribute to NAFLD or disease progression in those with NAFLD. With more confidence, we can now inform patients with fatty liver disease to follow a diet low in refined sugars, avoid extra sugar, and to be careful about fructose, particularly in the form of high-fructose corn syrup, such as in sodas and fruit drinks. I advise them to start reading food packages and labels.

What are the best options for medical management of NASH?

Diehl: Lifestyle modifications (diet and exercise) remain the mainstay of treatment for NAFLD. Studies are being done to identify drugs that help to reduce liver damage and prevent disease progression in NAFLD.

The first multicenter, prospective controlled clinical trial comparing two treatments -- vitamin E and the insulin-sensitizing medication pioglitazone -- to placebo was published May 2010 in the New England Journal of Medicine. Duke enrolled many patients in that trial as part of an NIH-supported consortium called the NASH Clinical Research Network.

In non-diabetic patients who had had a liver biopsy that showed NASH, both treatments were found to be effective: 18 months of treatment with either vitamin E or pioglitazone improved the histologic features of NASH (fatty cells in the liver and inflammation and swelling of liver cells).

As a result of this recent study, therefore, we now have two potential treatments for NASH in non-diabetic patients. More studies are planned to identify agents that will help NASH patients who do not improve with pioglitazone or vitamin E treatment, and to determine the best treatments for NASH patients who also have diabetes. The latter trials will be particularly important because it appears that diabetic patients with NASH are likely to develop cirrhosis.

Why do some patients with fatty liver disease get cirrhosis while others don’t?

Diehl: From our research at Duke in animal models and in people, we find that some people tolerate fat accumulation in the liver without activating signaling pathways that lead to serious injury. Hence, they stay at early disease.

Other people, for reasons that we don’t understand (some may be genetic, some may be environmental) go down a path that’s going to lead them to cirrhosis and liver cancer. We’re trying to understand why some people go one way and some people go the other.

Ultimately, as we learn more about the mechanisms that cause progression to more serious disease, we aim to not only develop therapeutics, but also blood tests to identify who’s at risk of progressing to more advanced stages of NAFLD. The latter will enable us to focus our attention on those patients who are at greatest need for treatment.

We have made progress in identifying proteins and pathways that play a role when patients develop the most serious forms of NAFLD. One of those is the Hedgehog signaling pathway, which is known to provide cells with information that is used to repair tissues, and which has been implicated in some cancers.

Hedgehog had never been identified before as playing a role in NAFLD, but we found that its activity correlates with NAFLD progression in animals and in people [published July 2009, Gastroenterology]. Now we’ve shown that manipulating the Hedgehog pathway in animals actually modifies disease progression in NAFLD. That’s exciting because some companies have already developed Hedgehog inhibitor drugs for use in other diseases. This is a totally new treatment area for NASH that hasn’t been explored before. Right now, it’s still at the pre-clinical stage, however.

We have also learned more about how the Hedgehog pathway works and interacts with other molecules. For instance, we have found that the Hedgehog pathway stimulates immune cells and certain types of liver cells to produce a molecule called osteopontin.

Other researchers at Duke in the Department of Surgery (Drs. Bruce Sullenger and Paul Kuo) have developed agents that block the actions of osteopontin. Using their agents in our animal models of NASH, we showed that inhibiting osteopontin blocked fibrogenesis [production of scar tissue in the liver].

Then we examined liver tissue samples that we have collected from our patients at Duke who have NAFLD. We found that osteopontin is turned on in NASH, and it’s at higher levels in people who have fibrosis than in people who don’t [published in the September 2010 Hepatology].

So, osteopontin may be a serum biomarker that helps us to recognize which NAFLD patients have more advanced liver disease. In addition, osteopontin might be another new therapeutic target in NASH. Studies are being planned to evaluate the safety and efficacy of osteopontin blockers in patients with NASH.

Duke Tissue Repository

Duke has created its own nonalcoholic fatty liver disease database and tissue repository with more than 1,200 patients currently enrolled. Participants donate small blood and tissue samples that Duke scientists use to develop new diagnostic tests and treatments for the disease.

Trials Currently Recruiting at Duke

A center of excellence in NAFLD, Duke offers patients comprehensive medical evaluations and management plans, as well as access to clinical trials of new treatments.

Duke is one of only eight clinical centers in the NASH Clinical Research Network, which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Clinical studies focus on prevention and treatment of NASH.

Current trials include:

A single-center trial to find out if the diabetes medication metformin in combination with vitamin E can improve NASH in non-diabetic patients.
A multicenter trial evaluating the role of a highly refined fish oil for treatment of NASH in diabetic and non-diabetic patients.

Additional diagnostic and treatment studies will be open for enrollment in early 2011.

For enrollment information, visit ClinicalTrials.gov.

Controversies in Medicine: Who Shall Live and Who Shall Die?

Fri, 21 Jan 2011 15:49:55 -0500

In the late summer of 2005, Dr. Anna Pou faced a horrendous and unanticipated moral and medical dilemma.

An attending otolaryngologist at Memorial Medical Center in New Orleans in the immediate aftermath of Hurricane Katrina, Pou had no electricity to power the apparatus of modern medical care, with the emergency generators having failed. Caring for large numbers of patients whose very lives depended upon those machines, and with no rescue in sight, she and the few colleagues who remained behind had to decide who should live and who should die.

Which of the acutely and chronically ill patients could be carried down the stairs to the helicopters and boats that might not arrive in time? Who should be permitted to suffer in unspeakable agony as the hours went by without any sign of relief?

Ultimately, she decided that she would ease their suffering using the only tools she had available -- morphine and midazolam. And for that, she was excoriated in the press and accused of murder by the state.

What happened after Hurricane Katrina was a national tragedy in which thousands died and many more lost their homes and livelihoods. Compounding the disaster was the poor preparation of the medical community for such an overwhelming catastrophe, with physicians like Dr. Pou being forced to make decisions for which they were prepared poorly, if at all.

While it might be tempting to argue that Katrina was a once-in-a-lifetime event, and that it’s improbable that doctors would have to cope with such a situation again, that seems like a meager rationalization for failing to prepare for another disaster.

Most recently, many doctors, nurses, hospital administrators, public health experts, and medical ethicists have been discussing and formulating plans for how to confront a possible influenza pandemic that could paralyze the medical system for months at a time, inundating health care facilities and providers with incredibly sick patients.

While the outcome of the 2009–10 flu season was milder than many expected, there is no reason to expect that we will not face such a situation in the not-too-distant future, or that the discussions that took place were in vain. Indeed, many of the topics that were the subject of argument and deliberation taught us to scrutinize what medicine can and can’t do, what we owe patients, and consequently what we should do in a crisis.

In other words, when we can’t try to save everyone, how do we decide whom we should attempt to save, and what, if anything, do we owe those who “lose” the lifesaving lottery? The answers to these fundamental questions stretch our moral selves to the limit. They force us to address issues that we rarely take time to think about in this country: concerns about rationing medical care and whether there are some lives that are more important than others.

Over the past couple of years I have given a number of lectures about this topic, using pandemic influenza planning to illustrate the problems. To demonstrate the profound difficulties in making decisions such as these, I have used the following scenario and table to challenge the audience in their thinking about how they would decide who lives and who dies if forced to make a choice.

Before reading the table below, imagine that you are in charge of triage at Duke Emergency Department (ED) during a flu pandemic. Many people, young and old, are presenting with incipient respiratory failure.

The ED is inundated with patients. Under normal times, when intensive care unit (ICU) beds and ventilators are almost always available, there is little discriminatory thinking required: if someone can physiologically benefit from mechanical ventilation, even in the short-term, and if there is not a valid do-not-attempt-resuscitation order in place, we intubate and resuscitate.

But what do you do when you have two patients in the ED at the same time whose vital signs are virtually identical, but you only have one ventilator and ICU bed available?

Who gets the chance to live? Who is relegated to die?

Who Will Live and Who Will Die?

Patient #1	Patient #2
21-year-old honor student	86-year-old nursing home resident
21-year-old honor student	40-year-old mother of three children
21-year-old honor student	21-year-old honor student
21-year-old honor student	21-year-old friend of a colleague
21-year-old honor student from Durham	21-year-old honor student from Fayetteville
21-year-old honor student and illegal alien	21-year-old honor student and U.S. citizen
21-year-old honor student	21-year-old honor dropout with police record
21-year-old basketball player	21-year-old with spina bifida in a wheelchair
21-year-old honor student	21-year-old with Down Syndrome

If you are like most people, these questions and their possible answers make you extremely uncomfortable. Not only does the way we address them reveal possible inner prejudices and potential cracks in our carefully crafted moral personae, but also demonstrates that we don’t have a clue about how we might act if we were in Dr. Pou’s shoes.

This thought experiment demonstrates the singular importance of open and inclusive discussion before such a crisis presents itself, so that the answers that are provided by the consensus plan do not compel doctors and nurses to face the choices in the table alone and unprepared.

Without proposing specific answers to these quandaries, we are not left without recourse. We can -- and indeed, should -- create plans that consider these horrendous scenarios and offer supportable and justifiable reasoning for choosing some people over others that are both fair and, as much as possible, evidence-based.

In point of fact, in the United States and in many other countries, a number of plans to deal with pandemic influenza have been crafted. Although most of these plans do not have specific advice on these questions, some do, for instance those of the VA system and the nascent plan created by the North Carolina Medical Society. Common features of these plans have included mechanisms to medically justify clinical decision making, using evidence-based medicine whenever possible.

Both the plans and the rationale for them need to be publicly vetted and acceptable, especially those parts that may have the most controversial, perhaps even noxious, statements. Given the uproar that accompanied the recent health care reform legislation, with talk of “death panels” and the like, it is vital that the process be transparent.

Furthermore, when adopted, the plans must affect everyone: it is a good practice of public justice that those who make the rules should also be bound by them. Hence, the relative of the hospital CEO does not have a greater claim on intensive care resources than someone who is possibly sicker and more likely to benefit. It may also be reasonable to advance the idea that some members of society are special, not necessarily because of who they are, but for what they do.

For instance, one could make a plausible argument that first responders and others who might justifiably profess to play vital roles in a health care catastrophe, such as police and firefighters, National Guard troops, ambulance drivers, doctors and nurses, and power plant workers should have first claim on such resources as influenza vaccine (as indeed was the case last year).

Finally, the primary mission of health care is the relief of suffering. And there is no question that a disaster such as a pandemic or another Katrina or a major terrorist event would produce human suffering on a massive scale. In the event of not being able to save everyone, we should prepare to care for those who are relegated to go without lifesaving treatment. This means training a wide variety of personnel in basic palliative, end-of-life care and stockpiling the drugs and other supplies that would be required to comfort the dying and relieve their suffering.

There is no guarantee that such plans will work as intended. But it is guaranteed that without a plan, human misery and anguish will be widespread, and moral principles that we rightly hold dear would be violated.

Careful discussions before the fact that include as many voices as possible will maximize the chances of how we, as a society, could successfully meet a prolonged emergency with our moral dignity both intact and strengthened.

Philip Rosoff, director of clinical ethics at Duke University Hospital, is a pediatric oncologist with a master’s degree in philosophy.

Duke’s clinical ethics service provides education to physicians, nurses, and house staff; generates policy and policy changes regarding ethical issues; and offers mediation to patients, families, and physicians when questions arise regarding such issues as end-of-life care, patient ability to participate in decisions, and futility.

A Pill for Every Ill: Managing the Pitfalls of Polypharmacy

Fri, 21 Jan 2011 16:09:01 -0500

In June 2009, Tonia Bass lost two things: her job and her health insurance. She had a variety of health issues and a collection of prescriptions to go with them -- between 12 and 15 at any given time, including vitamin supplements.

Bass is part of a growing patient population: those who take medications to manage two or more chronic conditions. Many of these patients have more than one prescriber, as well, which can create risk for drug-related problems caused by polypharmacy -- medications prescribed with no indication, adverse drug interactions, duplicate drug therapy, and non-adherence to treatment regimens.

Bass was able to participate in Project Access of Durham County, a program that connects uninsured patients receiving care at Lincoln Community Health Center (LCHC) to a local network of Duke specialists and others who donate specialty care.

In August 2008, the LCHC Pharmacy was accepted by a federal agency into a project focusing on medication reconciliation for patients in Project Access -- with the end goal of helping caregivers better understand patients’ medication needs, avert potential drug interactions, and make sure patients can obtain the drugs they’ve been prescribed and follow through on taking them.

Through this project, Project Access went from having a current, comprehensive medication list for only about 20 percent of its patients to 100 percent. “The key to our success was having a single point of accountability for all the services we were providing to Project Access patients,” says Duke’s Lynn Robbins, PharmD, project leader. “we designated a pharmacy care coordinator who makes absolutely sure that every service is provided for our patients.”

Duke University Hospital achieves the same single-source accountability by using electronic prescribing as its single central repository for drug ordering, says Philip Rodgers, PharmD, director of pharmacy education at Duke Area Health Education Center.

The health system also deploys Duke pharmacists into Duke clinic settings, such as primary care clinics, where the risk for errors and adverse effects related to polypharmacy can be high.

“We provide doctors and nurses with medication review and assist them in problem-solving,” he says, adding that there are also pharmacists based in Duke’s anticoagulation, lipid, and certain oncology clinics. “We are exploring opportunities to possibly deploy pharmacists to other clinics, such as transplant and other oncology areas.”

Three Ways Clinicians Can Help

Although patients are responsible for keeping providers informed about the medications they are taking, Philip Rodgers, PharmD, says there are three steps clinicians can take to help create an accurate medication list:

Acknowledge the medication information you have at hand is probably not completely accurate.
Conduct a thorough medication reconciliation review with the patient to prevent duplicate therapy or adverse drug interactions.
Call the patient’s pharmacy to get a list of medications other providers have prescribed and what medications the patient has been picking up.

Clinician Q&A: Vaccines at the OB–GYN Office?

Fri, 21 Jan 2011 08:13:56 -0500

Geeta K. Swamy, MDIf you’re an OB-GYN, you probably don’t think of yourself as being the source of booster vaccines for your patients. But maybe you should.

A new pilot study from Duke researchers shows that offering the shots to women who come in for their annual checkups can increase vaccination rates in both pregnant and non-pregnant patients. The program, funded by the U.S. Centers for Disease Control and Prevention (CDC), could serve as a guide for other OB–GYN clinics to boost vaccination rates.

DukeMed Magazine talked with Geeta Swamy, MD, director of obstetrics clinical research at Duke, about the pilot program’s success in North Carolina.

Why should OB-GYNs consider offering vaccines during annual visits?

We tend to think of vaccinations as happening at the offices of pediatricians, primary care physicians, and family practitioners. But many women seek medical care from their gynecologists even after they have children.

According to a study published in Obstetrics & Gynecology (March 1995), OB–GYNs provide more general medical care to adolescent and adult women than either family practice or internal medicine practitioners. So their annual gynecologist visit is a good opportunity to discuss preventive care, which includes vaccinating.

How did the program shift vaccination rates?

Initial data from one clinic show that doctors were already offering the HPV vaccine to women who weren’t pregnant, but when postpartum women were offered the vaccine, the rate of vaccination jumped from 0 to 44 percent. Without this program, these women would not have been vaccinated against a potentially life-threatening disease.

What vaccines were offered, and what were their results?

The pilot program was established mainly to improve the rates of vaccinations against human papillomavirus (HPV) among non-pregnant women and tetanus, diphtheria, and pertussis (Tdap) among non-pregnant and postpartum women.

The results of offering this vaccine were even more significant than expected. Nearly 600 women out of the 1,000 who were offered the Tdap vaccine for the first time received it.

Why is the Tdap vaccine important?

Reaching women who had not yet received the Tdap vaccine is important because rates of pertussis have been rising for the last five years. Pertussis isn’t as serious in adolescents and adults, but it is life-threatening to infants under a year old who haven’t been fully immunized. In fact, the CDC reports that mothers are the primary source of infection in 32 percent of infant pertussis cases.

When is the optimal time to give the Tdap vaccine?

Ideally, we aim to vaccinate women before they conceive, but any postpartum woman should get the vaccine if her last tetanus-diphtheria shot was more than two years ago. By vaccinating new moms, we can provide a cocooning effect that protects their infants from a deadly disease.

Cancer Vaccines: The Quest Continues

Fri, 21 Jan 2011 10:37:48 -0500

John H. Sampson, MD, PhDIn 2005, David Schmidt was diagnosed with glioblastoma multiforme (GBM), one of the most aggressive of brain tumors.

After surgery, radiation, and chemotherapy, his tumor had not yet recurred, but his doctors told him there was only a 3 to 5 percent chance that things would stay that way.

Today, five years after his symptoms first began, Schmidt is still recurrence-free. He credits that in large part to his enrolling in a clinical trial of a vaccine developed at Duke.

“Enrolling in the trial was one of the few options available. It was either that or just kind of take my chances and hope that the cancer didn’t come back,” Schmidt says. “The vaccine trial was attractive because the side effects were minimal. I’m doing really well.”

This vaccine “trains” immune-system cells to attack EGFRvIII, a protein that is present in 25 to 40 percent of GBMs.

In the phase two trial in which Schmidt was involved, patients whose tumors expressed EGFRvIII and who received the vaccine showed overall improved survival times compared to historical controls -- a median of 26 months, compared to 15.2 months. These patients also experienced a much longer progression-free survival period -- 14.2 months, compared to 6.3 months for those who did not receive the vaccine.

Findings published in the October Journal of Clinical Oncology showed that the vaccine eliminated all of the cancer cells carrying the EGFRvIII marker in all but one of the vaccine group participants, says Duke neurosurgeon John H. Sampson, MD, PhD. The results of that trial and others led to Duke licensing the vaccine to the pharmaceutical company Pfizer.

Sampson and colleagues are now honing a different type of weapon against GBM -- vaccines that aid the immune system’s fight against cytomegalovirus, which is normally latent in the body but that researchers at Duke and elsewhere have discovered is activated in some patients with GBM.

“Because the immune system is especially developed to attack viruses, this provides an unparalleled opportunity for us to exercise immune therapy against these tumors,” Sampson says. Duke is leading single-center phase one and phase two trials of glioblastoma vaccines that target cytomegalovirus.

Duke’s extensive work in developing and testing cancer vaccines means that patients can participate in trials of vaccines for many types of cancers -- brain, breast, colon, ovarian, and prostate.

Duke was an enrolling center for the trial that led to approval of the prostate cancer vaccine Provenge, which in May 2010 became the first cancer vaccine approved by the Food and Drug Administration.

New trials available only at Duke include a study of a vaccine called dHER2 to fight breast cancer that overexpresses the HER2 protein, which is one of the more aggressive forms of the disease. The trial was developed because of findings in mice that Duke oncologist Michael Morse, MD, and colleagues published March 1, 2010, in Clinical Cancer Research.

“We showed that if you use a cancer vaccine in conjunction with a targeted therapy [lapatinib], you get additional efficacy. The vaccine activates T cells and also multiple antibody responses against HER2 that synergize with the HER2 tyrosine kinase inhibitor lapatinib,” Morse says.

If that proves true in humans, the vaccine could improve upon standard treatments for this type of breast cancer, which include chemotherapy plus the monoclonal antibody trastuzumab (Herceptin). “Unlike trastuzumab, which binds to just one part of HER2, the vaccine induces polyclonal antibody responses, targeting different parts of the molecule,” Morse says.

Other work from Duke has also demonstrated the additive effect from combining traditional treatments with vaccines. “We’ve demonstrated in animals and humans that there is a potent synergy between chemotherapy and vaccines; the chemotherapy actually dramatically enhances the effects of the vaccine,” Sampson says.

For now, even after surgery, radiation, chemotherapy, and immunotherapy, recurrences are still all too frequent. But Sampson, Morse, and other Duke investigators work to develop the right combination of treatments that will make survival stories such as Schmidt’s more commonplace.

Learn more about clinical trials at the Duke Cancer Institute.

What We Learn from Bird Brains

Fri, 21 Jan 2011 11:14:55 -0500

Richard Mooney records the songs of birds who are learning to sing and compares their progress to activity in the young birds' brains-research that could unlock the mechanics of human auditory learning.The sound of songbirds in the morning can be an impromptu serenade. But listen closely, and it’s clear the birds aren’t improvising. They’re reciting and repeating a signature tune they learned in adolescence from the dominant male in their lives.

Those melodious tweets are entrancing, but why study how birds learn their music? According to Richard Mooney, PhD, a neurobiology professor and investigator at the Duke Institute for Brain Sciences, understanding what happens inside a bird’s brain when it hears and memorizes a certain song could lay a foundation to improving speech in humans with auditory disabilities.

“Birds use auditory experiences to guide behavior just like humans use hearing to guide speech development,” Mooney says. “If a young bird doesn’t hear a tutor song or can’t hear itself sing, it doesn’t develop a normal song.”

According to Mooney, who has spent the last 25 years studying the brain circuitry and neural pathways that control singing, a bird has a finite amount of time to be exposed to and learn a tutor’s song.

The juvenile bird needs to hear a tutor song during a developmentally sensitive period, similar to a human child’s need to hear language consistently in the first years of life in order to develop fluent speech. If a songbird does not hear the tutor song before two months of age, its brain becomes committed to producing a simple “isolate” song. The tutor’s song lasts for a few seconds, and adolescent birds only require a few minutes of exposure to the same song to memorize it. However, to produce an accurate copy of the tutor song, they must practice the song thousands of times over a month or more.

What makes some juveniles better song learners than others? Looking inside the bird’s brain can reveal the presence of dendritic spines, doorknob-shaped protrusions on a nerve cell that receive and process electrical signals from other nerve cells, at specialized junctions known as synapses.

By looking into the brains of naïve juvenile songbirds, Mooney and his colleagues found that the rate at which these spines come and go (spine turnover) could predict how well a juvenile would learn from a tutor. Juveniles with the highest levels of spine turnover were the best learners, while birds with stable spines learned little or nothing from their tutors.

To visualize living neurons in juvenile birds as they learn to sing, Mooney’s team first injects a brain area in the bird analogous to Broca’s area in humans with a fluorescent green protein. Then, using a scanning laser microscope, they peer through a small surgically implanted window in the anesthetized bird’s skull.

Cells expressing the protein glow green when struck by the laser light, allowing them to be visualized under the microscope. After obtaining a baseline measure of spine turnover, the bird is exposed to the tutor song. The imaging process can be repeated over many days and weeks as the bird slowly copies the tutor song. This approach allows spine changes to be monitored as the juvenile memorizes and copies its tutor’s song.

The effect of hearing and internalizing the tutor song was counterintuitive, Mooney says. “In those juveniles with high spine turnover, hearing a tutor song immediately stabilized spines, even though the copying process had hardly even begun,” he says. “It appears that in receptive juveniles, hearing a tutor song rapidly stabilizes and strengthens the synaptic network. One intriguing possibility is that we are watching the formation of a memory that sets the stage for motor learning.”

Mooney says the findings of this work ultimately will help explain how the human brain harnesses auditory information to guide learning of complex skills, such as speech and music. It could also help to explain how, as we age, our brains become less receptive to learning new skills, including foreign languages.

Anxious Times

Fri, 18 Jun 2010 14:10:04 -0400

Even if you’ve thus far managed to avoid a personal crisis via economic downturn, domestic or foreign violence, or plain-out natural disaster, the cultural pulse of dread that dominates our times is inescapable.

We’re still slogging through the aftermath of the worst financial crisis since the Great Depression. Our landscapes -- literal, financial, and emotional -- have been shaken by earthquake and oil spill. Job losses and home foreclosures continue to ripple through the media headlines, with no clear end in sight.

It seems that by the millions, Americans are facing agonizingly uncertain futures.

In times of trouble, heightened anxiety is an appropriate response, one that can spark positive action. A few sleepless nights of fretting over impending layoffs may well drive someone to more mindful spending, or even to develop a new set of skills to better compete in the marketplace.

Anxiety keeps humans alert to dangers both physical and social, so at its best it’s a powerful tool for survival.

But for those with anxiety disorders -- which affect 40 million adults in the United States, according to the Anxiety Disorders Association of America -- such sensations take on a life of their own, far removed from the events that triggered them.

Instead of spurring self-protective action, fear and dread become overwhelming, even incapacitating.

Personality vs. Pathology

“Imagine you’re sinking in quicksand while having a heart attack, and someone has stuck a loaded gun in your mouth,” says Liam. That’s how urgent and terrifying his panic attacks were when they struck.

“There was an impending sense of doom. That’s one of the worst things. You feel it will happen, that this is the end. My body isn’t working; I’m going to die.”

Eventually Liam learned he had mitral valve prolapse, which is associated with panic attacks, but the severity of his anxiety had by then eclipsed its origins. “It was completely debilitating. I had no control of my nightmarish racing thoughts, and no control of my body’s reaction to these thoughts.”

Carrie is a cancer survivor with a long career in a volatile industry, but it wasn’t until a confrontation with a supervisor four years ago that her struggle with anxiety began.

“I’d wake up in the morning and have this sense of dread, and every day it got a little worse. No peace, no sleep; the thought of eating was horrible.

"It felt like that fight-or-flight adrenaline had kicked in and never turned off. I could feel it in my stomach, a constant fluttering. I felt like all the areas of my life were out of control. I’d pace back and forth, praying for it to stop. You try to maintain this normalcy, but inside you’re screaming.”

To Liam and Carrie, it was clear that something physical had gone terribly awry. But the forms anxiety disorders take are not always so easily recognized.

In some people, the line between personality and pathology can be difficult to discern -- as with Tim, whose acute social anxiety was something he’d long taken for granted. He says he’d always been “introverted and shy. I thought, ‘This is who I am, this is the hand that was dealt to me,’ and for the most part I tried to accept it.”

A former tennis pro, Tim had felt at home out on the court, but found the frequent board meetings and presentations the job required “extremely challenging. Any time I was the center of attention, I don’t think I coped very well. I didn’t have any growth through repetition. I probably knew early on that the anxiety was interfering with my life, but I didn’t have the strength or the will to follow up -- maybe it was not even knowing how to follow up.”

But four years ago, as the date of his daughter’s wedding approached, he began to wonder whether something could be done to help. “I just wanted to enjoy the moment and be there as her dad.”

Wei Zhang, MD, PhD“People often think it’s a question of character,” says Wei Zhang, MD, PhD, director of the Anxiety and Traumatic Stress Program at Duke, which conducts research on anxiety disorders and provides adult outpatient care.

“They assume they’re just stressed out. Perhaps there has been some stressful event, the stock market’s down, there’s a death in the family, and they think they just have to tough it out. Or they think it’s natural because their mom was like that -- and, of course, anxiety disorder does have a genetic component.”

Roots of the Crisis

Social anxiety has been linked with a functional variation in the human serotonin transporter gene, which appears as either a short or long allele.

People who carry one or two short alleles are predisposed to a stronger emotional reaction to threat and fear, which sometimes manifests as anxiety. Among humans of European ancestry, 64 percent have at least one copy of the short allele.

But why should an allele that could bias individuals towards maladaptive emotional responses appear so frequently?

“It’s important to understand that the short allele is advantageous under most circumstances, largely through its positive effects on arousal and attention,” says Duke neurobiologist Ahmad Hariri, PhD.

Hariri is studying variations in the serotonin transporter gene that may account for up to 10 percent of the difference in the reactivity of the amygdala -- the structure in the brain that is crucial to both the formation of emotional states and the encoding of memories that have an emotional component, such as those of a traumatic event.

These genetic differences may help explain why one person reacts to a stressful situation with a debilitating depression, anxiety, or post-traumatic stress, when another does not.

“Maybe evolution favors this genetic constitution in particular environments characterized by uncertainty or volatility,” suggests Duke neurobiologist Michael Platt, PhD. Platt’s research group studies the social behavior of rhesus macaque monkeys, who are the only other primates with similar variation in the same gene.

“Being more easily aroused might promote more risk-taking behaviors outside of the social realm, like leaping farther between trees or traveling farther,” he says -- behaviors that contribute to the success and survival of individuals carrying the gene.

The variation could also offer protection in certain social situations. A recent study by Platt’s group showed that macaques with the short/long allele combination, like humans, become averse to risk when experiencing social anxiety. This may aid them in avoiding dangerous interactions with others.

“There’s a heightened vigilance in social situations,” explains Platt, which could benefit a low-status monkey, “although someone high in status who is risk-averse may not take advantage of opportunities or resources available.”

Identifying and understanding genetic predispositions to anxiety disorders could one day pave the way for more tailored and effective therapies. “We may be able to get to who is most at risk for these disorders and even to find the biological pathways where we could intervene to prevent the disorders from ever occurring,” Hariri says. “To shift these trajectories before they even begin to manifest, that’s the dream.”

However, genes are not destiny, Platt is quick to emphasize. “This is not deterministic. A lot depends on environment. A traumatic childhood experience, for example, an uncertain or deprived upbringing -- that’s when the short allele starts to have a bigger negative impact.”

Shifting Symptoms

If an anxiety disorder is triggered in childhood, it can present very differently than it does in adults, and its appearance shape-shifts with maturity.

Richard D’Alli, MDDuke child and adolescent psychiatrist Richard D’Alli, MD, chief of the Division of Child Development and Behavioral Health and medical director for Child and Adolescent Psychiatry Services, says identifying it is “really about adjusting your sights as a clinician to the developmental stage of the child. Anxiety might look like excessive fussiness in infancy.

"Toddlers may show anxiety by being inhibited or behaving in a way that is avoidant. When they get to pre-K or kindergarten, separation anxiety can be the issue, when they throw massive tantrums and may refuse to go to school or be away from their parents.

"In adolescents you may see the anxiety manifesting as social phobia [also called social anxiety disorder, or SAD] -- isolation from friends, or not participating in the classroom out of fear so that it affects grades.”

Substance abuse may emerge at this stage as well, as an attempt at self-medicating. What separates the difficulties almost all children experience from a true disorder that calls for intervention is impairment.

“When we say someone is impaired, we really mean that they are in some way prevented from doing their developmentally appropriate job,” observes D’Alli. “What’s the job of a kindergartner? To go to school, to stay in circle time, to take naps, to eat with the other kids, to be a family member.”

Similarly, in adults, the threshold between distress and disorder is functional impairment, says Zhang. “It’s when you could achieve more in your life without that fear and avoidance.”

“The sooner any kind of medical or psychological disorder can be identified and treated, the better the long-term outcome,” says D’Alli. “No one questions that about cancer. We ought not to question it in pediatric psychiatric disorders, of which anxiety is one of the most prevalent.”

Trading in the Benz

The first-line drug treatment for a range of anxiety disorders is SSRIs or SNRIs (selective serotonin and norepinephrine reuptake inhibitors). While some physicians may be tempted to try benzodiazepines, lured by this older class of drug’s promise of quick, short-term relief from panic symptoms or insomnia, “they carry a lot of baggage,” warns Zhang.

Potentially addictive, benzodiazepines also have been shown to worsen depression, which commonly co-exists with anxiety. They are emphatically not recommended for post-traumatic stress disorder (PTSD), says Zhang, because they impair the ability for cognitive restructuring, which is important in recovery from PTSD.

And according to D’Alli, they’re not appropriate for children: “At present there are no data to support long-term treatment of child and adolescent anxiety with benzodiazepines.”

Compared to benzodiazepines, efficacy and safety are much better established for SSRIs and SNRIs, Zhang says. Still, only 50 to 60 percent of adult patients experience some symptom relief from the medication. “The rate of complete remission is even lower -- about 30 to 40 percent. And remission should be the ultimate goal of treatment.”

The psychotherapy approach of cognitive behavioral therapy (CBT) has also proven to be beneficial for anxiety, especially PTSD, notes Zhang. “A lot of studies bear that out. However, alone it is not always sufficient, especially when symptoms are severe. A patient unable to concentrate, for example -- how much is he going to be able to absorb in CBT?”

Studies have shown greater efficacy with medication and CBT combined than with either alone. Combined therapy has also been proven effective in children.

Duke researchers led by principal investigator John March, MD, took part in the Child/ Adolescent Anxiety Multimodal Study (or CAMS, published in October 2008 in the New England Journal of Medicine), which showed dramatic improvement in chidren with separation anxiety, generalized anxiety, or social anxiety disorders that were treated with both sertraline (Zoloft) and CBT. Medication and therapy taken separately showed efficacy as well.

The study’s authors further noted no suicidality among the participants -- a reassuring finding for physicians and parents disturbed by the black-box warning that remains on SSRIs specifically because of concerns about suicidal tendencies among young patients.

Nonetheless, medication need not always be the first step in treating children’s anxiety, says D’Alli. “Some very good news that we have from CAMS is that CBT has just as much a chance of being effective in the treatment of pediatric anxiety as any evidence-based medicine.”

To increase the probability of a more robust response to treatment, a combination of SSRI with CBT is indicated. But if there are concerns about medication, says D’Alli, it serves to start with the therapy: “There is no black-box warning on therapy!”

Diagnosis Dilemmas

Anxiety disorder is significantly more widespread than depression -- one-third of the population will experience anxiety disorder in their lifetimes, as opposed to the one person in five who will suffer major depression. However, anxiety hasn’t achieved anything approaching the level of public -- or professional -- awareness that depression has.

This diagnosis disparity may exist because of how people with anxiety disorder commonly present. “Oftentimes patients will come in with vague somatic symptoms, such as headache, nightmares, fatigue, or irritability,” notes Zhang. “Sleep disturbances are common: night waking, waking in a cold sweat or panic. Or they don’t have the sense of being rested and refreshed -- they may not even realize their sleep quality is not good.”

Chest discomfort, muscle tension, or GI symptoms are also red flags, and even less likely to be linked to a psychiatric condition.

“Anxiety disorder has a lot of overlapping symptoms with chronic fatigue, fibromyalgia, and irritable bowel syndrome. You can treat the symptoms, but if you don’t treat the underlying cause, patients may still come back with those symptoms. More tests may be run, and doctor and patient are both left scratching their heads."

Careful, directed questioning can help primary care physicians to identify a potential anxiety disorder -- and it’s possible to do so within the time constraints of the average exam. A brief but effective screening tool is the Generalized Anxiety Disorder-7 (GAD-7) and its subscale, the Generalized Anxiety Disorder-2 (GAD-2). Both perform well in screening not only for GAD, but for panic disorder, SAD, and PTSD.

“Some very simple screening questions can help you narrow down the cause,” adds Zhang. “The most important thing in recognizing PTSD, for example, is identifying a history of trauma -- that’s the center of the issue. It’s very important to ask about whether there has been a very stressful event. PTSD is oftentimes missed even among the psychiatric community; it’s treated as GAD or depression, and they’ve missed the elephant in the room.”

Anxiety is also often a co-morbid condition. Patients frequently have multiple anxiety disorders or experience acute anxiety alongside depression, bipolar disorder, or addiction. In these cases, tailored treatments, optimally under a specialist’s care, are needed.

For Liam, who struggled for years to head off his brutal panic attacks without shutting off from the world, connecting with the right specialist was key. “He saw past the anxiety and zeroed in on what no one else had recognized, that it was a part of bipolar disorder.”

The Gradual Recovery

But even then change didn’t happen overnight. As his specialist gradually fine-tuned his medications, Liam worked on getting regular exercise and eating more healthily, lifestyle changes he feels helped stabilize him as well.

The difference, he says, is “night and day. Now, I can do most of the things I could do before. That doesn’t mean I don’t ever get anxious or fear a panic attack, but it’s like having a second chance at a normal life.”

For Carrie, a six-week medical leave allowed for intense therapy and careful medication management, which helped stabilize her enough to return to work. Within four months she was feeling more like her old self, and “today couldn’t be more different,” she reports. “I am more at ease with myself.”

Tim’s first step toward recovery was volunteering for a Duke study on SAD. He later sought treatment through the Anxiety and Traumatic Stress Program. Drug therapy has provided dramatic relief of his symptoms, he reports.

“The medication offers me an opportunity to be comfortable in situations where I wouldn’t otherwise be.”

Now a sculptor by trade, he’s still often the center of attention, attending gallery openings and delivering presentations and Q&As. But unlike in his tennis years, “there’s no trepidation going forward, only positive anticipation and excitement. I am seeing a different side of myself -- it’s illuminating.”

Helping patients find their way to normal lives is what drives Zhang and her colleagues, whether that means feeling like their “old selves” or tapping into new, unprecedented selves.

“In the face of trauma or stress,” she observes, “people can and do overcome their fear with help. Human beings have a lot of resilience.”

Clinician Q&A: Peripheral Vascular Disease

Fri, 18 Jun 2010 14:56:38 -0400

Manesh Patel, MDPatients over the age of 70, or patients over age 50 who have diabetes or a history of smoking, are at high risk for peripheral vascular disease (PVD) -- but probably don’t know it.

Although more than eight million Americans have this condition, in which atherosclerotic plaque builds up in vessels outside the heart and brain -- most commonly resulting in reduced blood flow to the legs and feet -- many have no symptoms, or they mistake the signs for something else.

Though the disease has long been recognized as an indicator of increased risk for cardiovascular and cerebrovascular disease, some of the recommendations for evaluation and treatment are shifting along with improvements in technology.

Cynthia Shortell, MDDukeMed Magazine asked three specialists to discuss the current options for diagnosis and treatment of PVD:

Manesh Patel, MD, cardiologist and assistant professor of medicine at Duke

Cynthia Shortell, MD, professor of surgery, chief of vascular surgery, and director of Duke’s Center for Vascular Disease

Tony Smith, MD, professor of radiology and division chief of vascular and interventional radiology

Tony Smith, MD

Why should patients with only mild or few symptoms be evaluated and treated for PVD?

Patel: The risks associated with PVD are not solely related to the legs but to the heart and the brain. More than half of people who have PVD also have severe coronary disease. When we take care of patients, our first goal is to reduce the risk for heart attacks and strokes.

While not all patients with PVD will have leg pain, claudication (pain or numbness in the legs that occurs when walking and resolves with rest) is certainly the most common symptom. Any patient with claudication should be evaluated, even if they don’t currently have heart disease, because PVD can be a precursor to heart disease.

Are there other indications besides claudication that my patient may need PVD evaluation?

Shortell: All patients with heart disease, cerebrovascular disease, smoking history, and diabetes are at high risk for having PVD, but the issue of whether or not they should all be screened is controversial. If a patient’s distal pulses are absent on physical exam, they definitely should be evaluated.

My patient has diabetes and already clearly has problems in his small blood vessels. Why would he need further evaluation?

Patel: Even these patients may still benefit from an evaluation of their large blood vessels. Otherwise, it’s like saying your problem is due to blockages in exits off of Interstate 40 without looking at 40 itself.

Opening up the big pipelines can still help these patients, and in many cases stave off amputation. Unfortunately, there are patients who go to amputation without anyone ever evaluating the blood flow to the large vessels in the leg.

When should my patient with PVD be referred for an interventional or surgical procedure?

Shortell: Patients should have failed conservative management before having a catheter-based or surgical procedure. That management is similar to treatment of atherosclerosis and would include aggressive control of blood sugar, lipid-lowering and antihypertensive treatment, antiplatelet therapy, and thorough foot care.

Also, smoking cessation is very important. Smoking has been shown to increase the risk of PVD as much as seven times. A sustained exercise program to build new vessels and improve circulation works the vast majority of the time. But of course, it’s harder to achieve than a procedure.

Sometimes medications can be useful, but we don’t have any medications that are excellent. For example, we have cilostazol (Pletal), which improves blood flow in the vessels. Fifty percent of the patients who take that medication are able to walk 50 percent farther without symptoms.

But many patients who take this drug experience side effects including GI upset, headache, and palpitations, and it’s contraindicated with cardiac arrhythmias and patients who have a history of congestive heart failure.

If a patient is still experiencing symptoms after maximal medical therapy, then she should be referred for a possible surgical intervention.

What has changed in terms of the procedures available for patients who need surgical intervention?

Smith: There are a lot of interventional therapies we can offer for patients who have chronic problems with PVD, including some patients who in the past would have actually gone to amputation.

For instance, we can revascularize the entire lower extremity percutaneously, which means we can open up the superficial femoral artery through catheter-based procedures that use balloons and stents.

Five years ago, we usually revascularized only very short areas of narrowing or occlusion. But today improvements in equipment and skill sets allow us to revascularize much longer segments.

The other option is of course to perform a bypass graft around occluded arteries. or, sometimes hybrid procedures are appropriate. Hybrid procedures can be performed in the cardiac catheterization lab or in the operating room and involve a surgeon making a surgical incision to get into the vessel, then using catheters to open up the vessel without doing a full surgery.

Shortell: In many cases, physicians will want to delay such interventions, because their benefits are durable but not permanent.

For example, in a young patient, a physician may not want to use up the patient’s saphenous vein for a bypass in case the patient were going to need it for a heart or lower leg bypass down the road. We usually reserve bypass for severe cases of claudication, or cases of critical limb ischemia, which means if an intervention isn’t performed, the patient is at risk of losing their leg.

Are there special interventions for these patients at risk for limb loss?

Patel: Duke has formed a Limb Salvage Center for patients who have critical limb ischemia -- which presents as resting leg pain or a non-healing ulcer.

Physicians can contact Duke Vascular, either cardiology, surgery, or interventional radiology, and we’ll see them in clinic and determine if there are ways to get more blood flow to their legs, and also make sure we’re coordinating our efforts with wound care specialists.

As part of the work of that center, for patients who have no other options to get blood flow to their legs, Duke offers enrollment in a clinical trial that uses stem cells to try to generate growth of new vasculature. This trial uses a therapeutic known as Pluristem, which is made up of undifferentiated placental stem cells. These cells are injected into the legs in an attempt to promote growth of new blood vessels and reduce pain for these patients.

What is changing for patients who need interventions for PVD affecting the carotid artery?

Smith: The gold standard of care for carotid artery disease is surgery (endarterectomy), in which an incision is made in the neck and the plaque is physically removed from the artery.

A less invasive option is carotid stenting, which is performed by inserting a catheter into an artery in the groin that is then threaded to the carotid artery. Currently, carotid stenting is approved by medicare and by third-party payers only for patients for whom surgery poses a high risk.

For patients not at high surgical risk, the literature has been inconclusive as to whether stenting provides outcomes that are equal to those from surgery.

But the results of CREST, a major study announced in February 2010 at the American Stroke Association’s International Stroke Conference, may change the playing field. CREST was an NIH-sponsored study with more than 100 centers involved, including Duke.

This was the largest randomized clinical trial to date comparing the two approaches, and it required rigorous training and credentialing for the physicians who performed the surgeries and stenting, in order to get a true comparison between the procedures.

The CREST results showed that carotid stenting essentially works just as well as surgery for patients who would normally undergo endarterectomy). In this trial, the overall stroke rates and long-term effects were similar for both procedures.

These results were a milestone, but at this point, we don’t know how Medicare and insurers will respond. Based on this study, they may in fact open it up and say a patient can choose whichever procedure they want. But we will have to wait a period of months to find out the decision.

Patel: In the meantime, patients who aren’t at high risk for surgical complications may be able to access carotid stenting through another clinical trial at Duke.

I’m the principal investigator at Duke for ACT 1, which is comparing carotid stenting with endarterectomy in treating asymptomatic patients at standard surgical risk. We have enrolled more than 30 patients in this trial and are still recruiting.

How does a doctor know what type of specialist to refer a patient to?

Smith: We have a great multidisciplinary effort between the Departments of Surgery, Medicine, and Radiology here. When patients come to the Duke Vascular Group, they get an opinion from all of us -- non-invasive cardiovascular medicine as well as endovascular and open surgery.

Patel: Sometimes, at other institutions, when you are referred to a surgeon you will most likely get a surgical procedure, or if you go to cardiology, you will get a catheter-based procedure. At Duke, we work together to figure out the best procedure for the patient, if a procedure is needed.

But as a general guideline, patients who have both heart and vascular disease may benefit from seeing a cardiologist first. If a patient has had prior surgical procedures or is considering surgery elsewhere and is at risk for surgical complications related to vascular disease, especially if they have non-healing wounds, they may benefit from a referral to a surgeon.

Controversies in Medicine: Direct-to-Consumer Genetic Testing

Fri, 18 Jun 2010 16:09:11 -0400

Geoffrey S. Ginsburg, MD, PhDThe appeals of the leading companies that sell direct-to-consumer (DTC) genome scans are hard to resist, especially in this age of the ever-more informed and increasingly "take charge" patient.

With one small saliva sample and a fee, a buyer can learn whether he or she has genetic traits that are associated with the most common killers of our time, from heart disease to diabetes to cancers of all kinds.

It is fair to say that these firms provide accurate and scientifically valid genetic-testing results from the samples provided by their customers. But there is also evidence that the interpretation of the genetic results may differ from one firm to another.

Moreover, although it might be useful to know one’s possible genetic predispositions toward developing heart disease or other conditions, there is still much debate within the medical community and the scientific literature as to whether this information is ultimately beneficial.

Just this May, plans to sell the first over-the-counter DNA testing kits at Walgreens were put on hold after the Food and Drug Administration questioned their legality; the agency is also examining online sales of similar tests, which continue to be available as of this writing.

One side of the debate argues that information gleaned from DTC tests may be motivating to patients -- it may change their behavior and help them make more informed decisions about lifestyle and medications.

In fact, the REVEAL study recently reported that children of patients with Alzheimer's disease were not only interested in having their ApoE4 (Alzheimer’s susceptibility gene) genotype measured, but also had less stress for having done so. Many even made decisions about long-term care insurance based on the results.

The other side suggests that the data thus obtained provide only limited information about a patient’s true risk profile -- which makes them potentially misleading, possibly causing patients to make needless decisions or creating stress and anxiety. The tests also could create false security among patients who don't show genetic risk for some diseases that could still develop.

At this point in the evolution of the field of personalized medicine, it is clear that patients who wish to "take control" of their health should do so in collaboration with their health care provider.

And because physicians and other medical professionals can play an important role in counseling individuals who are contemplating DTC tests or have already taken them, it behooves the physician community to become aware of the different DTC tests on the market, their nuances, and their potential value for the individual.

Putting Genetic Risk into Context

One of the clinician’s primary goals when discussing these tests should be to help the patient see these test results as just one risk indicator in the universe of data that doctors maintain on their patients.

Genetic information is best placed in the context of other clinical information, with one of the most important being a thorough family history.

Patients should also know that most of the genetic data gained from current state-of-the-art DTC tests are incomplete. Many of the inheritable tendencies of consumer interest -- one's likelihood of getting diabetes, for example -- are based on numerous genes that work together in the development of, or in providing protection from, the condition in question. But current tests detect abnormalities in only a few of these genes. Tests do not yet exist for most of the others, nor does knowledge about how they all work together, or sometimes fail to.

This point may be confusing to patients who are familiar with the mendelian-genetics tests that already exist, such as those for cystic fibrosis or Huntington's, diseases that are the result of a single gene.

But given the genetics of complex diseases such as cancer, diabetes, and heart disease, the presence of one or even several abnormalities does not have a "no doubt about it" aspect and may actually be inconsequential. And if, for argument's sake, we did know all of the genes involved in a particular medical condition, and a test were available for each of them, and the telling mutations proved to be present, there would still be other factors, such as lifestyle and diet, that influence the outcome.

"Genes load the gun," it has often been said, "but environment pulls the trigger."

How best to interpret the results of genomic scans is also an area of significant uncertainty. A study in the October 8, 2009, issue of Nature, which compared two companies' results from the same individuals’ samples, found little difference in the accuracy of the genetic analyses done by the DTC testing outfits, but several differences in the reporting of risk.

This finding does not impugn the test providers so much as it illustrates that medicine is still as much an art as a science -- a reality not unique to the field of genomic and personalized medicine. Uniform industry-wide standards obviously need to be developed. But even under the best of circumstances, genetic test results and the interpretations that go with them should not be taken as gospel.

By the end of the next decade or so, it's possible that personal genomic testing could move from a boutique business serving the few who are interested and can afford it to a technology that is fully integrated into health care.

The benefits for both patients and providers could be enormous: imagine a health care system, for example, that could sequence virtually every person’s genome -- if possible, at birth -- thereby giving each person a lifelong tool for prevention, diagnosis, and treatment of the diseases he or she is most likely to develop.

Providers could work with their patients to formulate individually tailored health plans, be more strategic in their interventions, and use limited resources more effectively to improve people's health and reduce their risks. This is, in essence, what personalized medicine is all about.

At this point much work still needs to be done before we can fully explore such possibilities.

In the meantime, it is important for physicians to educate themselves in this exciting and uncertain new world. To do so, we need not all become experts in the details of genetics or even know which genes are being analyzed in any given case.

Clinicians should even consider simply having their own genomes scanned. This action would, more than any course or literature search, change the abstract concept of DTC genomic scans into a personal reality. It would also give clinicians a wider and richer perspective to bring to the patient-physician relationship, as physicians' and patients' understanding of genetic-testing innovations mature together.

Opinions expressed in Controversies in medicine are those of the author and do not necessarily represent Duke medicine as a whole.

Geoffrey S. Ginsburg, MD, PhD, is the founding director of the Center for Genomic Medicine in the Duke Institute for Genome Sciences & Policy. He is also a professor of medicine and in pathology at Duke University Medical Center.

Questions for the Chair: Mary Klotman, MD

Mon, 21 Jun 2010 12:33:36 -0400

Mary Klotman, MDMary Klotman, MD, became chair of the Duke University Department of Medicine on March 1, 2010. An accomplished scientist and clinician, she previously held the position of chief of the Division of Infectious Diseases at Mount Sinai Medical Center in New York for 13 years.

This is a return to Duke for Mary -- she earned her undergraduate and medical degrees, completed her residency and a fellowship in infectious diseases, and then served as assistant professor of medicine here.

She is married to Paul Klotman, MD, also a Duke medical alumnus and still the chair of the Department of Medicine at the Mount Sinai -- they communicate with each other and their two sons, away at college in different states, via Apple’s iChat video conferencing software. Mary sat down with editors from The Abstract, Duke Medicine's faculty newsletter, to talk about her first weeks on the job.

How did you prepare for this new role?

I’ve had a lot of preparation. I’ve lived with a department chair for eight years -- I cannot underestimate how important that has been. I was also division chief for 12 years, and that combination exposed me to the broad array of issues in a large academic health care system.

The other big thing I had relative to Duke is that I made a decision about 10 years ago to get involved in the medical alumni association. I had not been really engaged with Duke once I left, because I was so busy raising a family and getting my career going. But about 10 years ago somebody asked me whether I wanted to be on the medical alumni council.

And that, over the last 10 years, has exposed me to all the big initiatives at Duke, such as creating the Duke Global Health Institute and when Duke was putting in the first CTSA grant.

That was great for me, because not only could I see what was going on at Duke, but I could compare it to what I was doing in my present job, to a very high standard. I don’t know why I made the decision, it wasn’t that I really needed to be back at Duke, but it was really a great professional decision -- I had the wonderful opportunity of meeting Dean Andrews through that.

Given that exposure to Duke, was there anything surprising once you started in the job?

The size of the Duke health care system is something that you can’t appreciate until you’re on the ground trying to figure out operations.

What I always loved about my job at Mt. Sinai was that if there was an issue, I knew exactly who to go to. I knew the structure. I knew what processes were in place. That’s the learning curve I have here.

For instance, if I want to do a quality initiative, learning what the structure of quality improvement is, I just have to find out who the players are in the department, how the department works with the hospital, how the hospital works with the health system. That’s the challenge. Every day I’m asking who does this, whose office is this, who is responsible.

What goals have you set for the department?

The broad strokes are reorganizing the department’s administration so that we are very, very responsive to needs of the faculty. One key component of that is a method for communicating back and forth.

Clinically, it’s going to be working with the PDC and working with the hospital to reorganize some of our practices. Some of that is being driven by health care reform, which is really exciting.

It means being a good partner with the health system and the PDC in anticipating changes and implementing those changes across the XX of practices within Medicine. So that’s going to require a structure that works.

We need to be more responsive because there’s change occurring right before our eyes.

What’s your biggest challenge in steering Medicine through these changes?

There’s no question going forward that the Department of Medicine in any institution is central to all the missions. To me that’s an overwhelming responsibility but also an exciting opportunity. And there’s no better place to be chair than at Duke, where you have the most incredible talent at every level.

So I feel that I’m very lucky to be here, and very lucky to have Nancy Andrews as my dean. I’m used to deans who are looking for the short term all the time, and Dean Andrews definitely has a much longer vision for the institution, which is very important in this time of both fiscal pressure and transition in health care.

A chair who thinks she is going to walk into an institution and get free rein on $50 million is not the reality anymore. The reality is that you must be a responsible fiscal manager, and I take that role extremely seriously. That is just the reality whether you are managing the clinical operations or the science or the teaching.

It is my responsibility to be fiscally responsible for the department. I don’t think that’s going to change in my lifetime as chair.

What strengths will you build upon?

Duke has all of the basic skills that any institution would need to respond to change. It certainly has the academic mass, as well as an incredible hospital and practice. Everything is there.

The big attraction for me is putting it together and working with the organization.

The other big challenge that is going to be fun is building translational research. It’s already very strong, but that’s where the growth will be, such as translational research around the oncology institute, which is a new and exciting venture. I’ll be working a lot with Rob Califf, who’s got great ideas for which Medicine is an important part.

And a lot of my working with Dean Andrews is identifying candidates to fill key research positions for building translational research. That’s like being a kid in a candy store -- you have this incredible patient population, incredible clinical service, great physicians and basic scientists, and my job is to look for opportunities to bring them together more.

How will you encourage collaboration and multidisciplinary initiatives?

A lot of that historically has worked at the ground level, individuals finding each other. But as the institution has gotten bigger and bigger, and my department has gotten bigger and bigger, that finding of the right partners has gotten challenging.

So my role, I think, is to be the point person to make those connections, particularly for some of the junior faculty and even from the day that a faculty member starts.

Basically, it’s being matchmaker who looks at an individual faculty member’s research area and thinks about what kinds of colleagues and collaborators this person going to need, because nobody does it alone anymore.

But how will you keep track of 500 faculty members?

I’m very fortunate that I have an incredible group of division chiefs. I will rely on them to make sure I meet who I need to meet, and I’ll be partners with them if we know there’s a retention issue and we need to work on keeping a faculty member. So that’s the first level.

The other level I’m trying to do right from the start is organizing smaller groups to interact with. A particular group of interest for me are the young K-awardees, the faculty who have their first level of grant support.

I’ll also schedule lunches with different groups, which gives me an opportunity to hear from them about their needs and how the department can better serve their career development. And, every time I hear about somebody who has a talent who might help the department, I’m doing a one-on-one.

So I’m mixing one-on-ones, small group lunches, and meetings with division chiefs.

I’m amazed at how many people I know already. Of course, there are challenges to meeting all faculty, not only the number but geography. I value the VA Hospital, which is an incredible resource, and I’ve already been over there. But I’ll have to put a lot of effort in making sure I engage faculty who are in different locations, such as primary care physicians.

Do you plan to continue your own research on the molecular pathogenesis of HIV-1 infection?

My first job, of course, will be being chair of the Department of Medicine. That’s something you have to accept when you take these kinds of jobs, it’s about being the chair first and not about my own career.

But I do plan to keep up my research. I kept my lab up at Mount Sinai, and I participate in lab meetings and data sessions using iChat. I probably will not physically move it here for the first six to eight months. I think realistically after a year I’ll be able to strike a balance.

I’m passionate about my research and I love the area of infectious diseases. It’s hard not to be interested in infectious diseases in general and HIV in particular. It’s such an engaging area, and has been for my whole profession.

The first case of HIV that I saw was as a house staff here in 1983 -- a young man was dying of overwhelming tuberculosis, and HIV wasn’t even identified yet. I feel like my generation really lived the epidemic, which is a tragic but amazing story. I like to think that my research is relevant, and obviously that piece was a big attraction to coming here too, because of CHAVI and Bart Haynes.

Who Needs a Mammogram?

Thu, 25 Mar 2010 09:50:23 -0400

On November 16, 2009, the U.S. Preventive Services Task Force (USPSTF) recommended new guidelines on screening for breast cancer, including mammography and breast self-exams. The guidelines were met with considerable debate. “Very smart, reasonable people review evidence and see different things,” says Duke breast oncologist Gary Lyman, MD.

New guidelines, new controversies— just give us the facts, please!

“Any recommendations regarding screening -- whether for breast cancer, prostate cancer, lung cancer, or others -- are going to be met with differing opinions because the recommendations ultimately are based on differing value judgments,” explains Duke radiologist Daniel Sullivan, MD, who was a member of the 1997 NIH Consensus Panel that considered this same question (whether or not to recommend breast screening for women ages 40 to 49). “What is important to one person may not be as important to another, in terms of risks and benefits.”

“It is a complicated and complex issue and many well-respected experts have strong opinions,” says oncologist Amy Abernethy, MD, who heads the Duke Cancer Center Research Program.

While physicians and researchers will most likely continue to debate the issue, there are a few questions that women can get answers to now:

The discussion and debate regarding mammography guidelines can be confusing. What do the experts agree upon?

According to Lyman, Sullivan, and Abernethy, there are several points that most physicians seem to agree upon:

No screening test is perfect, and we always need to develop better ones.
Although we have made progress in our knowledge of breast cancer, we need to know more so that we can prevent occurrence. Until that time, we must continue our quest to determine how to treat every woman’s breast cancer in the most effective way possible.
Without a doubt, every woman should be familiar with her own breasts and should report any changes or concerns to her physician.
Each woman should talk to her physician about mammography and should be allowed and encouraged to make her own decisions about whether or not to have a mammogram.

What do the new USPSTF guidelines recommend?

In terms of traditional mammography, the task force recommends against routine screening mammography in women ages 40 to 49; their guidelines say the decision to start regular, biennial screening mammography before the age of 50 should be an individual one and take into account the patient context, including her judgement about specific benefits and harms.

For women ages 50 to 74, the task force recommends mammography screening every other year. The task force also concluded that there is not sufficient evidence to warrant screening mammography for women 75 years and older.

The task force concluded that there was also insufficient evidence to warrant clinical breast exams and also recommended against clinicians teaching women how to perform breast self-exams.

Lastly, the task force concluded that there was insufficient evidence to assess the potential benefits and risks of digital mammography or magnetic resonance imaging (MRI).

What mammography guidelines do other organizations recommend?

Many groups -- the American College of Radiology and the Society of Breast Imaging, the American Cancer Society, the American Medical Association, the National Comprehensive Cancer Network, the Canadian Task Force on Preventive Health Care, and the American College of Obstetrics and Gynecology -- recommend that women ages 40 to 49 continue to have yearly or every other year mammograms.

The American Academy of Family Physicians recommends that decisions about mammography in women ages 40 to 49 should be based on an individual’s risk for breast cancer, while the World Health Organization recommends mammography every one to two years for women ages 50 to 69.

Do the new USPSTF guidelines deny any woman the ability to get a mammogram?

No. The task force doesn’t say that women should avoid mammograms. Instead, the task force “encourages individualized, informed decision-making about when to start mammography screening.”

The recommendation against routine annual screening does not apply to those women who are at an increased risk for breast cancer by virtue of a known underlying genetic mutation or a history of chest radiation.

Will insurance continue to pay for mammograms for women ages 40 to 49?

Most likely. On December 3, 2009, the Senate approved an amendment to its health care reform legislation that would require health insurers to cover mammograms for women ages 40 to 49. At the time of this article’s publication, the health care reform bill was not yet final.

What is the USPSTF?

The U.S. Preventive Services Task Force is sponsored by the Agency for Healthcare Research and Quality, part of the U.S. Department of Health & Human Services.

The task force makes recommendations about which preventive services for numerous diseases should be incorporated routinely into primary medical care and for which populations. The task force does not set federal policy and it does not determine what services are covered by the federal government.

Who are members of the USPSTF?

The USPSTF is a task force that comprises physicians specializing in a variety of areas, including epidemiology, internal medicine, and family medicine. View a complete list of task force members and their credentials.

Duke Medicine's Plan to Expand

Mon, 23 Nov 2009 14:03:59 -0500

Cranes, bulldozers, and a corps of construction workers have swarmed onto the Duke University Medical Center campus, signaling the start of an ambitious expansion project designed to dramatically enhance the experience of patients, families, students, and staff at Duke for decades to come.

Following rigorous rounds of project reviews and approval by the State of North Carolina, Duke Medicine leaders announced in August 2009 their decision to move ahead with the historic initiative, which has been on the drawing board for several years.

"Duke Medicine is all about people -- it's about the patients we serve, it's about the people who work here to deliver the best care, discover new things, and train the next generation," says Victor J. Dzau, MD, chancellor for health affairs.

"To support those people in the years to come, we must make sure that we have the state-of-the-art facilities we need to provide the best care and the best environment to work and learn in."

This vision is now becoming a reality with the official start of two landmark buildings. Together, the new Duke Cancer Center and the Duke Medicine Pavilion, along with related renovations, will add more than 800,000 square feet of space, with 160 intensive- and intermediate-care inpatient rooms, 16 new operating suites, 130 exam rooms and 75 infusion spaces dedicated to cancer care, and expanded and updated imaging platforms. Total project costs are estimated at more than $700 million.

Planning is also under way for a new School of Medicine learning center that will provide an optimal environment for medical student and interdisciplinary team training. The larger, modernized facilities are greatly needed not only to accommodate an increasing demand for patient care, but also to support the broader vision for medicine at Duke, according to administrators.

The new facilities are thoughtfully designed to:

Improve the patient experience by making clinic visits more efficient, increasing inpatient room size, better accommodating visitors and family members, and providing amenities such as resource centers, healing and spiritual spaces, and green spaces
Support multidisciplinary care by co-locating a wide range of providers within fast-growing specialty services such as cancer and heart
Accommodate leading-edge clinical technologies including advanced imaging and diagnostic equipment and linear accelerators for cancer radiation therapy
Enhance education and research by providing state-of-the-art facilities that support training, facilitate study of new techniques and treatments, and bring clinical research teams closer to patients
Incorporate advances in information technology to improve communications between clinical teams and individual patients -- not only within each building, but across the continuum of Duke Medicine services and sites

Although the global economic crash in 2008 diminished Duke’s capital reserves,
Duke Medicine leaders remained committed to moving ahead -- describing the efforts as a mission-critical investment in the future.

"Without expansion and modernization, the quality of our patient care could suffer and our long-term goals could be significantly stunted," Dzau says.

"Years of conservative and prudent fiscal management, combined with careful cost-cutting measures, have put us in a strong position to move forward with these projects -- which we believe are essential to our ongoing ability to meet the growing demand for patient care services and to conduct cutting-edge research and training in an era of population growth and accelerating innovation.

"At heart, we believe we have a responsibility to meet our patients' needs for high-quality health care in the years ahead."

In addition to institutional investment, fund-raising initiatives have been launched to raise $75 million toward the costs of the Duke Cancer Center, $50 million toward Duke Medicine Pavilion, and $15 million toward the learning center, which is also supported by a $35-million gift from The Duke Endowment.

"The vision for the future of the campus is to continue to support what makes
Duke Duke: excellence in clinical care, teaching the next generation of all kinds of providers, and generating innovations that we can push through the enterprise," says Kevin Sowers, RN, MSN, CEO of Duke University Hospital.

"It's about supporting incredible people who work here every day and do incredible things in people’s lives, by giving them facilities designed to enhance their efforts to care for Duke's surrounding communities, the residents of North Carolina, and beyond."

Training Spaces

Besides serving hundreds of thousands of patients every year, Duke University Medical Center is also home base for one of the country’s largest health-care training programs, with more than 900 medical residents and fellows on the house staff, plus more than a thousand students in the medical, nursing, physical therapy, and physician assistant programs. The planned campus expansion will benefit these next-generation caregivers as well as the patients they’ll serve:

State-of-the-art technology from new linear accelerators in the cancer center to interoperative imaging technologies in Duke Medicine Pavilion’s surgical platform will allow clinicians to better practice -- and therefore teach -- to their full potential, facilitate research that will improve care and support training of academic physicians, and enable trainees to gain experience in cutting-edge care.
A School of Medicine learning center located in the heart of the medical center campus -- the first new building dedicated to medical education since 1930 -- is being planned to provide the team-oriented, technology-based experiences today’s curriculum demands. “New learning space for our students was the top priority for our own leadership and the main recommendation during our recent accreditation process,” says Dean Nancy Andrews, MD, PhD. “Medical education has changed dramatically since our current facilities were built. The vision for this new space is to provide our students with the laboratories and training facilities that will best help them prepare for their future careers.”

The new buildings have been preceded by new facilities for the School of Nursing (completed 2006) and the physician assistant program, which in early 2009 moved into a freshly renovated building designed to accommodate future growth.

Read more about the planned learning center in the summer 2009 issue of DukeMed Alumni News, online at medalum.mc.duke.edu.

Duke Medicine Pavilion: Answering Demand for Surgical and Intensive-Care Services

Since its current bed tower opened in 1980, Duke University Hospital has grown not only in patient volume but also in reputation as one of the most advanced hospitals in the country. And frankly its success has the 29-year-old building bursting at the seams.

From Monday through Friday, the hospital fills at least 90 percent of its 924 inpatient beds, many of them with critically ill patients sent here for the best medicine has to offer.

A 2005 study showed Duke's OR usage to be 93 percent -- compared to 80 percent for the average academic medical center. And with every upgrade to new technology, Duke electricians and IT experts have to figure out how to rearrange the guts of the building to support the state-of-the art tools in play.

The plans for the new Duke Medicine Pavilion -- a 580,000-square-foot addition to the hospital housing OR suites, intensive care units, step-down units, and diagnostic facilities -- have focused on maximizing flexibility of space and technology, leaving Duke Medicine room to grow.

Operating Space

The 16 new OR suites will be larger than the current operating rooms in order to accommodate advances in technology that enhance precision and safety. The new suites are designed to be flexible, allowing both multipurpose and specialized use: interoperative MRI and CT are located between suites, for instant access that won’t crowd the room when not in use.

A hybrid OR is already under construction in the current hospital, and will open in 2010; it will allow interventional cardiologists and surgeons on-the-spot, highly detailed vascular imaging capabilities -- and enable easy transition between catheter-based, minimally invasive, and open procedures within the same space.

Built-in technology will enable the surgical team to review critical information without going to multiple places or even stepping away from the table: multiple plasma screens will allow surgeons to review x-rays and other imaging studies, as well as pathology specimens.

"Duke’s surgical faculty are nationally and in many cases internationally respected, and demand for their services is exhausting our current facility," says Danny Jacobs, MD, MPH, chair of the Department of Surgery.

"The Duke Medicine Pavilion will be critically important to our ability to meet surgical demand and train the next generation of surgical leaders."

Roomier Rooms

Duke Medicine Pavilion’s 96 critical-care and 64 intermediate-care beds won’t just add more space, but better space -- reflecting dramatic changes in care since the hospital’s Anlyan bed tower was built.

Then, patients arrived for surgery the night before the procedure; their families awaited results in the waiting rooms and sat with their loved ones in brief stints during visiting hours. Today families want to stay with patients around the clock, and the new patient rooms are designed to accommodate more people -- clinicians and family alike.

These and other features of Duke Medicine Pavilion reflect input from current patients, families, physicians, nurses, and other staff, says Mary Ann Fuchs, RN, Duke University Health System's chief nursing officer.

"The building’s entire layout will allow patients much more access to their families, allow the staff more interaction with patients, and allow the staff to work in a more streamlined fashion. We strove to create a place where multidisciplinary teams could work well together and where patients could feel comfortable and cared-for."

High-Tech Hospital

In addition to upgrades in the OR, a high-tech, centrally located imaging center will streamline access to MRI, CT, and nuclear testing for patients and clinicians. The building will also accommodate new tracking and electronic medical record (EMR) technology, enabling better coordination of care within the hospital, across the health system, and beyond Duke.

"Most medical errors and patient safety issues emerge when a patient transitions from a hospital to a primary care setting," says Asif Ahmad, chief information officer for the health system.

"Our EMR technology already coordinates a patient’s information among all three of our hospitals; our plan for this building is to go ‘EMR-plus’—to use technology to improve patient education and help prevent glitches in the translation of information when they leave the hospital."

Patients -- and Providers -- in Motion

The layout of the hospital -- as well as the cancer center -- began with studying all the traffic that flows through current service areas, from shift changes to patient transport.

For example, neurology patients have to go for CT scans frequently, so designers worked to locate the neurology ICU near CT. And all heart services throughout Duke University Hospital will be located on the same level, regardless of what building they are in.

A two-story concourse -- just about the same width as an airport concourse -- will be the "Main Street" that connects Duke Clinic to Anlyan Tower. The totally enclosed and climate-controlled concourse will simplify the journeys of patients and staff as they move around the medical center.

Healthful and Healing Spaces

Great care is being taken to create an environment that is pleasant and supportive for patients and their families. A major component of that philosophy is linking patients to the world beyond the facility walls -- by providing green spaces that can be seen from patient rooms and waiting rooms alike.

The Duke Medicine Quadrangle: The doors of the cancer center and the new hospital addition will open onto a park designed by Laurie Olan, the landscape architect who redesigned both Columbus Circle in New York City and Philadelphia’s Independence National Historic Park. Similarly designed courtyards within the hospital will provide more green views for patient rooms.

Patient resources: The main doors of the hospital addition will open into a two-story entryway that leads visitors to a patient library, a café, and a quiet meditation or reflection space.

Letting the sunshine in: The overall facility design brings natural light into staff and patient-care areas. "That actually is really helpful to patient and staff morale," says Fuchs, "just having a pleasant environment in which to do our work."

Green in more ways than one: Besides its visual connection to the outdoors,
Duke Medicine Pavilion -- targeted for LEED Silver status -- is designed to be environmentally friendly, with green roof space, sustainable building materials, and energy-efficient mechanical systems.

Duke Cancer Center: Creating the Optimal Experience for Cancer Patients

When Harry Rhoads was diagnosed with stage 4 melanoma three years ago, his Duke oncologist told Rhoads he most likely had about 11 months to live -- but that he could join a clinical trial of a promising new interleukin drug.

The treatment schedule would be difficult: two weeks of treatment and two weeks off, for a total of six treatments. Each round of interleukin was followed by "six days of hell," Rhoads says -- nausea, vomiting, hallucinations.

"I was scared."

But PET scans showed that the tumors were shrinking with each session. Despite a few setbacks, Rhoads is cancer-free today.

Rhoads’s experience of cancer treatment isn’t representative of all cancer patients; as every tumor type is unique, every cancer patient has his or her own treatment experience. But in many ways, Rhoads says, "every patient goes through the same thing" -- a complex balancing act of fear and faith, suffering and grace.

Rhoads lives near Washington, DC, so his choosing Duke for his treatment went beyond the considerations of distance and convenience.

William J. Fulkerson Jr., MD, Duke Medicine’s senior vice president for clinical affairs, says patients like Rhoads travel to Duke for access to world-class specialists and the promise of the newest and most comprehensive treatments for the disease that threatens their lives.

As one of only 40 National Cancer Institute-designated Comprehensive Cancer Centers in the nation, Duke offers options that simply aren’t available in many hospitals.

"There are two things that set academic medical centers like Duke apart from other health care organizations," says Fulkerson. "One is that highly focused specialists from many disciplines work together under one roof to provide comprehensive care; the other is that academic medical centers are in the business of bringing innovation to the table as quickly as possible."

The impetus for building Duke Medicine’s new cancer center facility, say its leaders, is to continue to deliver on that promise to an ever-growing number of patients. By more closely integrating clinician and clinical research teams, the design of the building seeks to promote the best of academic medicine’s multidisciplinary and research-driven nature.

In addition, the space must provide the most healing, patient-centered environment possible to support patients like Rhoads as they go through the journey of fighting, living with, and surviving cancer.

Combining these mandates of form and function is a tall order -- and that's why the vision for the project goes far beyond adding square footage. In fact, leaders say, the goal is nothing less than to create the best possible cancer treatment experience.

What Makes "Multi-D" Work?

A key part of that is enhancing the multidisciplinary approach that distinguishes cancer care at Duke -- and that studies show is associated with better patient outcomes. But the buzzword multidisciplinary has multiple meanings.

Depending on the cancer type, multidisciplinary care at Duke might mean having different specialists working in the same space on parallel schedules for easy "collaboration on the fly," or it might mean scheduling clinicians around each patient -- such as in the Duke Prostate Center, in which a newly diagnosed patient is visited by a surgeon, radiation oncologist, and medical oncologist who confer with each other to develop a coordinated, comprehensive care plan.

And then there is the expertise of specialized nurses, nutritionists, psychologists, social workers, and physical therapists, all of whom work in concert to provide Duke cancer patients with whole-person care.

If the fuel that powers these many modes of multidisciplinary care is the talent pool of the clinicians on staff, then the rate-limiting factor is space -- which in Duke’s current buildings is growing tighter due to swelling patient volume and the continual introduction of new and better imaging and radiotherapy technology.

This is why the most talked-about feature of the new building is space: 267,000 square feet of it, including ample room to bring clinicians, counselors, and research staff from their current far-flung locations into dedicated space closer to patient exam rooms.

"Physicians want their patients to have multidisciplinary care that doesn’t require coming to Duke three or four times to see different doctors," says Carolyn Carpenter, the health system’s associate vice president for oncology services.

"Adding space to our facility will allow us to schedule patients and clinicians in a way that's more efficient -- and that will lead to a better experience for the patient."

Designed to Heal

Not only the exam rooms but the entire building is designed to deliver an ideal patient experience. Planners began by mapping out all the stops cancer patients have to make during a visit to Duke, from registration and the pharmacy to mammography, MRI, labs, chemotherapy, or radiation therapy.

"Then we went to focus groups [of Duke cancer patients] and said, 'Here’s what we think the experience is like. Do we have it right? And what would you change?'" says Sowers.

The central premise behind every focus group -- and there were several -- was how to make cancer care revolve around the patient instead of the patient's disease.

In the case of radiology, for example, patients didn’t want to have to walk to one part of the building to get a CT and then another to get an MRI, as they do in the current facility; in the new building a full floor of the cancer center hosts all of the radiology platforms in one consolidated area.

When patients enter the new building, they'll be welcomed by a resource center -- no long registration queues or full waiting rooms in sight. The boutique, food court, and outdoor spaces are designed to provide pleasant options for patients who are waiting before or between appointments.

And the waiting areas themselves are designed to accommodate comfortably both the patients and the family members who travel with them.

"We did studies of how many people typically accompany a clinic patient and an infusion patient," says Carpenter. "And we used that information to determine how big our waiting areas should be."

Betty Lamar, a member of Duke Cancer Institute’s Citizens Advisory Council, says the intangible effects of a patient-friendly atmosphere make all the difference -- and she should know. Her first husband died of leukemia, while her second had bladder cancer, and she experienced the full spectrum of cancer care in a variety of clinical settings.

As a veteran caregiver, Lamar says she’s seen how cancer treatment has shifted over the years to a patient focus.

"At Duke they are now really treating the whole person and not the disease," she says. "It didn’t use to be like that, it was all focused on the disease."

Lamar serves as a volunteer at Caring House, a home away from home for many Duke cancer patients. She says she has seen many patients and families who reflected her own experience.

"They would arrive so afraid and anxious," she says. "They came from all over the country and world. They were desperate for help."

Room to Advance

The draw for these patients is often the clinical trials offered at Duke, such as the interleukin trial Rhoads is part of. In fact, Duke is currently conducting more than 700 cancer trials.

"Cancer care, almost more than anything else that we do at Duke Medicine, is a fast-evolving field -- new treatments and new understandings emerge all the time," says Fulkerson.

Clinical trials are what drive these discoveries into cancer care practice, and the studies are "fundamentally intertwined with clinical care," says breast oncologist P. Kelly Marcom, MD.

"We need efficient clinical space to ensure a seamless approach to clinical research, as well as patient care. With the new building, we will have additional space to educate patients about clinical trials and accrue individuals to participate in these trials."

The new building will include dedicated space for clinical trial consultation and coordination, making standard what was previously a rare luxury for clinical trial coordinators -- complete privacy and uninterrupted quiet space near patient exam rooms to discuss clinical trials, informed consent, and any questions a patient has about clinical research.

Also, says radiation oncologist and Duke oncology services medical director Christopher Willett, MD, the new building will house brand-new, first-in-world imaging and radiotherapy technologies that will supplement both patient care and research.

"In addition to expanding the space and bringing in more tools, we are intensifying our focus on the patient’s experience. The new building will be more efficient for them and for us -- and very user-friendly. I think that all of us feel extraordinarily positive about the plans for it."

Lamar made the first gift to the Cancer Center building fund, which Duke hopes will raise $75 million toward the project’s estimated $220-million cost.

"Where you're treated is a very important part of treatment and cure -- it's important to be in a happy place," she says. "And the new building will really make you feel that way.

"It’s a place that makes you realize that you’re being considered as a whole person."

This article was first published in the Fall 2009 edition of DukeMed Magazine.

Dueling Guidelines

Mon, 23 Nov 2009 13:41:17 -0500

Erik Paulson, MDAlthough colon cancer has been well-publicized as the second leading cause of cancer deaths in the United States, only about half of the people who should get screened for the disease actually do.

It’s not hard to imagine why: colonoscopy, the current gold standard for screening, is no fun. The rigors of “bowel prep.” Sedation. An endoscope inserted into the colon. But in 1993 a less invasive option came on the scene -- "virtual colonoscopy," or CT colonography, which involves the same bowel prep as colonoscopy, but neither sedation nor scope.

"We insufflate the colon with carbon dioxide, and in a single breath-hold take a CT scan of the abdomen," says Erik Paulson, MD, chief of abdominal imaging at Duke.

"Then the study is over. After the procedure, patients can return to work."

Physicians at Duke offer CT colonography as a clinical option, participate in its development, and train physicians in its use. Some studies suggest that CT colonography is comparable with colonoscopy in terms of effectiveness for most patients, especially when weighed in terms of its comparative ease.

But it isn’t perfect; even the major organizations that promote colon cancer screening have not yet recommended it as the procedure of choice for routine screening for average-risk adults.

In 2008, in the first-ever joint guidelines for colon cancer screening, the American College of Radiology, the American Cancer Society, and the U.S. Multi-Society Task Force on Colorectal Cancer specifically included CT colonography among several recommended options for screening and prevention in average-risk adults.

These guidelines differ from those issued that same year by the U.S. Preventive Services Task Force, which express doubt about the widespread accuracy of CT colonography because most physicians still have little experience with it.

A Big Change in Coverage

For some patients, the dueling guidelines won’t matter because of a practical issue -- payment. Medicare and Medicaid, as well as some insurance companies, still do not cover CT colonography for patients at average risk for colon cancer. Some private insurers do cover CT colonography, but coverage is variable.

Medicare and Medicaid pay for the procedure only for patients whose condition makes a standard colonoscopy riskier than usual, such as if they’re taking anticoagulants or can’t be sedated for some reason. It may be covered for patients who have had an attempted colonoscopy that wasn’t completed because of bowel blockage.

In addition to colon blockage being a reason for an incomplete colonoscopy and appropriate referral for CT colonography, patients with tortuous (twisty) colons may have an incomplete colonoscopy and be appropriate referrals for CT colonography.

Those rules aren’t likely to change soon. In a final decision released in May 2009, Medicare and Medicaid announced they would not cover CT colonography for routine screening. But some private insurance companies have begun paying for CT colonography for routine screening for patients 50 and older.

"That’s a big change," Paulson says. Multiple studies showing that CT colonography rivals colonoscopy are what have turned the tide.

Paulson points in particular to a multi-institutional trial published September 18, 2008, in the New England Journal of Medicine.

"That study showed that the sensitivity and specificity of CT colonography is competitive with colonoscopy," Paulson says.

In the study, 2,800 patients underwent CT colonography and then a colonoscopy, and the CT version identified 90 percent of patients with polyps or cancers that were 10 millimeters or more in diameter.

Some previous studies, including one at Duke in which Paulson was involved (published in Lancet in 2005), showed that while CT colonography was good at detecting actual cancers, it was not as good as colonoscopy at detecting polyps.

But Paulson says the technology has since made big leaps thanks to advances in bowel preparations, the three-dimensional technology used to interpret the scans, computer-aided detection software which increases the accuracy of interpretation, and the ability to label residual fecal matter in the colon so it doesn’t show up on the test.

He and other Duke researchers have studied the technique -- leading research including multi-institutional clinical trials, the causes of false-negative and false-positive interpretations, and evaluation of computer-aided detection software.
Duke Radiology has for the past five years offered CT colonography as part of its routine clinical practice.

"We have six radiologists in our department who are skilled and experienced at CT colonography," Paulson says. "We’re doing more of them now than we’ve ever done."

Colonoscopy: Still the Gold Standard

Joanne Wilson, MDDuke gastroenterologist Joanne Wilson, MD, does think that less-invasive tests can increase screening rates.

"Definitely the biggest impact something like CT colonography will have is getting more people screened who are at average risk," Wilson says.

But she sees the technology as one that’s not ready to be widely implemented.

"CT colonography has promise, but there probably needs to be some further development of the technology," she says.

Also, many current physicians aren’t prepared to offer the procedure.

"One of the points raised in the literature is that radiologists who were trained just in standard CT would need to gain additional training in order to conduct and read CT colonographies," Wilson says.

"When new technology is introduced, there’s always a concern about how you’re going to train currently practicing physicians."

Wilson also points out that if alternative tests such as CT colonography or stool tests come back positive, the patient likely will have to have a colonoscopy anyway in order to remove or sample the lesion.

"The colonoscopy is both diagnostic in the sense that you can see polyps, and it’s therapeutic because you can take them out, or you can mark them or sample them. The final diagnosis of cancer is a histological diagnosis; you want to look at the tissue with the microscope," she says.

She also emphasizes that colonoscopy will remain the recommended test for patients at high risk for colon cancer -- those with a prior history of colon polyps and colon cancer and those with a family history of polyps and cancer.

Paulson acknowledges that colonoscopy is still the tried-and-true gold standard.

"There’s no doubt that colonoscopy is a great test," he says. "For many people it makes all the sense in the world. But as good as it is, it has some risk and requires sedation and is more invasive."

And, he says, while colonoscopy is a mature technology, the virtual version can be expected to continue to make technological leaps.

This article was first published in the Fall 2009 edition of DukeMed Magazine.

New Angles on AFib: Innovative Treatments and Research

Mon, 23 Nov 2009 13:39:51 -0500

Atrial fibrillation (AFib) is the most common heart arrhythmia. It’s also among the most challenging to control -- first-line therapies don’t work for up to half of patients, raising their risk of heart failure and stroke.

By pinpointing the often-mysterious origins of AFib, fine-tuning drug strategies, and pushing the boundaries of catheter ablation, physicians in Duke’s new Center for Atrial Fibrillation are now restoring healthy heartbeats in more than 90 percent of patients -- and counting.

The heart’s beat begins with an impulse. The sinoatrial node -- our natural pacemaker -- generates electrical signals that travel through the atria and into the ventricles.

These signals set off synchronized contractions in each chamber of the heart, creating the comforting lub-dub sound of the heart’s pumping as it trades spent blood for a freshly oxygenated supply.

Atrial fibrillation (AFib) is the most common disruption of this powerful rhythm, affecting around 2.2 million Americans. It can stem from coronary artery disease, high blood pressure, structural heart defects, or even arise seemingly out of the blue.

Whatever the cause, abnormalities in the heart’s electrical system make the atrial chambers contract too quickly -- up to 350 times per minute. This quivering in the atria causes chaos in the ventricles, which react with a flurry of rapid, irregular beats. The lub-dub becomes more like a pitterpat -- one that is disconcerting at best, life-threatening at worst.

For some patients, AFib is barely noticeable: they have mild symptoms, such as fatigue, or no symptoms at all.

Others feel their hearts racing or experience frightening episodes of heart palpitations. These individuals often live in dread of such events: they don’t want to travel or go to work or school. Others give up exercise and other activities that could trigger the irregular beats.

"AFib symptoms and the anticipation of the episodes are so dramatic for some patients that it almost turns their lives upside down," says James Daubert, MD, the new director of the Duke Heart Center’s electrophysiology (EP) program.

Even worse than unpleasant symptoms, says Daubert, the irregular rhythm can contribute to heart failure, while ineffective pumping allows blood to pool in the ventricles and atria -- turning the chambers of the heart into a breeding ground for blood clots.

In fact, atrial fibrillation is responsible for about 15 percent of strokes.

Managing these symptoms and sequelae has long been a hit-or-miss proposition. The usual front lines of defense -- drug therapy to alleviate the arrhythmia and prevent stroke -- are often ineffective or fraught with complications.

But recent advances in understanding the physiology of AFib are leading to new treatment strategies, including safer, more effective medical management and sophisticated catheter ablation techniques that are providing a new alternative to drug treatment.

At Duke, electrophysiologists, cardiologists, cardiovascular surgeons, and other specialists on the forefront of these efforts are banding together to mount a new attack on AFib -- the Duke Center for Atrial Fibrillation (DCAF).

"The spectrum of therapies necessary to treat AFib today falls under different specialties, and we created the DCAF to draw on our depth of resources," says the center’s director, electrophysiologist Tristram Bahnson, MD.

"As treatment for AFib becomes more precise and personalized, we are bringing together a convergence of specialists to formulate how best to care for each individual patient."

A New Aproach to AFib

Treatment of AFib usually begins with a constellation of drugs, each selected to slow the heart rate, restore the heart’s normal rhythm, or prevent stroke. But medical management of AFib can be problematic.

More than half of patients treated with antiarrhythmic drugs report recurrences of atrial fibrillation within a year of the start of treatment, according to several nationwide studies. And when not used carefully, these drugs can actually trigger dangerous heart rhythms or other serious side effects.

For example, one of the most effective antiarrhythmics, amiodarone, can produce side effects such as skin discoloration, photosensitivity, thyroid imbalance, liver inflammation, or decreased lung function in as many as 30 percent of patients who take the drug for long periods. It also can interfere with the action of anticoagulant drugs, which most AFib patients should take to help prevent stroke.

And while antiarrhythmic drugs may improve symptoms, they do not improve mortality rates compared with those of AFib patients treated with rate-control drugs such as beta-blockers.

Catheter ablation, which cauterizes and neutralizes small spots of heart tissue that generate abnormal electrical patterns, is gaining ground as a strategy to help AFib patients who don’t respond to antiarrhythmic medication. According to a collective review of six smaller studies published in 2003 and 2004, roughly 80 percent of patients in their 50s and 60s who received the minimally invasive procedure were free from recurrent episodes.

"In the past, people who could not get good control of their AFib with medication just had to suffer the symptoms as best they could or perhaps undergo major surgery," says Bahnson.

Today, with catheter ablation as a proven alternative for patients who have failed drug therapy, the Duke team is able to control symptoms in more than 90 percent of people seeking treatment, he says. The DCAF currently performs the highest volume of AFib catheter ablations in North Carolina, and Bahnson expects the procedure’s popularity to grow.

Although it’s just coming into its own as a treatment for AFib, ablation to treat other abnormal heart rhythms has been around for several decades. In fact, cutting or removing pieces of heart tissue to cure arrhythmia was pioneered at Duke.

In 1968, a Duke team performed the first successful ablation surgery to treat abnormal heartbeats in a 32-year-old fisherman who had Wolff-Parkinson-White syndrome -- a disorder that causes AFib or other fast heart rhythms.

In 1987, James Cox, MD, a cardiothoracic surgeon at Barnes-Jewish Hospital in St. Louis who had trained at Duke, showed that he could cure AFib by making and then suturing multiple incisions in a grid-like pattern of lines through the atrial chamber walls -- a technique known as the Cox maze procedure, or simply "maze."

The idea was that the incisions would leave lines of scar tissue that could act as barricades, blocking impulse propagation in the heart chamber and preventing AFib from being sustained. Maze surgery is still performed to treat AFib, but usually in conjunction with other major open-heart surgery.

The maze surgery was complex and daunting to imitate with a catheter, says Daubert, who was in training at Duke around that time. When Cox introduced the surgery, many assumed that the electrical source of atrial fibrillations originated within the atria itself.

That idea was challenged as other doctors tried maze and discovered that the pulmonary veins were usually "the money spot" for the origin of the abnormal heartbeat.

"The discovery that it was coming from the pulmonary veins made catheter-based treatment a more feasible target," Daubert says.

Other strategies were also being tested, such as the use of implantable cardioverter defibrillators, or ICDs, to shock the heart and restore normal rhythms. For patients with ventricular arrhythmias, which are sometimes accompanied by atrial fibrillation, ICDs are commonly used, and the devices have been shown to reduce the incidence of sudden cardiac death in patients with heart failure.

In the late 1990s, researchers tried ICDs as a therapy for atrial fibrillation. While the devices worked to shock the heart back into normal rhythm and to reduce the frequency of AF episodes, the shocks were painful and were needed too often to make the treatment practical, Daubert says.

In the late 1990s, Daubert and others did their first catheter ablations to treat atrial fibrillation. It was slow going in this early stage of the technique: they would put the catheters in the heart and wait for the first signs of abnormal activity. Was it coming from the left pulmonary vein, or the right? The doctors would leave the catheters in different regions of the heart, sometimes for hours.

They tried to speed the process along by artificially pacing the heart into AFib and then restoring normal rhythm with a shock, hoping to stir up the sites that led to a recurrence of AFib.

"The problem was that sometimes [the fibrillation] wouldn’t happen during that procedure," Daubert says. "Sometimes, it would come from one vein and we’d ablate there, but another day it would come from a different vein and we hadn’t ablated there."

Over the next few years, it became clear that electrophysiologists needed to ablate around all four pulmonary veins, regardless of where initiating arrhythmias were observed. By then the potential benefits of the treatment began to crystallize.

Better Ablation

Bahnson is also encouraged by the rapid development of ablation and the potential for the technique to improve lives. In fact, the results are so promising that they raise the question of whether ablation could become a first-line therapy for atrial fibrillation.

However, Bahnson cautions, a few important unknowns remain about the procedure’s long-term effectiveness. Bahnson is one of the principal investigators of a large, multi-site investigation coordinated by the Duke Clinical Research Institute that will compare catheter ablation with drug therapies for initial treatment of atrial fibrillation.

"This study will likely be a definitive one to determine whether mortality or stroke rates in AFib patients are improved by catheter ablation as compared to treatment with medications only," says Bahnson.

Meanwhile, Daubert is beginning research that will look at outcomes of ablation treatment in older patients.

"Most patients with AFib are in their 70s or even 80s," he says. "We don't have a lot of data as to whether the ablation is as safe or effective in this group as it is in younger patients."

Catheter ablation does come with risks and challenges. For example, in rare cases, the ablation procedure itself can cause blood clots and subsequent stroke. In other rare instances, parts of the body, such as the esophagus, can be injured during the procedure.

Researchers in the DCAF are investigating a range of novel technologies to make catheter ablation safer and more effective. For example, Duke recently began working with a new system, Hansen Medical’s Sensei X Robotic Catheter System, which allows catheters to be manipulated with greater control and precision within the heart. Outcomes research is under way to establish the value of this system and develop it further.

Other DCAF research is testing arrhythmia-mapping techniques to identify areas that should be targeted for ablation and to determine when enough ablation energy has been delivered at any given site within the heart.

"A big question in the catheter-ablation arena is how do you know when you’ve created a lesion in the heart that’s sufficient?" says Bahnson.

The DCAF group is now assessing catheter-created lesions in real time, working with Duke bioengineers on intracardiac ultrasound techniques that image the heart from within.

Various types of catheters in development might also make ablation safer and easier. Duke physicians are working on one new type that freezes heart tissue instead of cauterizing it, as with radiofrequency ablation. Daubert says the technique, called cryoablation, may make ablation safer than with traditional methods.

"If we’re ablating too close to the pulmonary vein, we could cause it to scar or narrow," Daubert says. "With the cryoablation, that problem is almost completely eliminated."

Another new type, an irrigated catheter, has six pin-sized holes at the tip that can be flushed with saline to prevent the catheter tip from overheating, thereby reducing the risk of blood clots. Both new catheter types, Daubert says, may help minimize the risk of stroke.

New techniques may also make catheter ablation for AFib more efficient. Daubert is currently experimenting with inflating a balloon at the opening of the pulmonary vein, which allows physicians to ablate all the way around the vein using radiofrequency energy or freezing techniques, rather than having to make small lesions, point by point, sometimes over the course of several treatments.

Personalized Rhythms

Despite the impressive advances in catheter ablation, the procedure may not be necessary or appropriate for all patients.

"There are so many players that act in the development and continuation of AFib," says Patrick Hranitzky, MD, director of the EP fellowship program at Duke, who is leading research to better understand the condition.

"It’s very difficult to decipher what all the contributors are," which can make it tough for physicians to select the best treatment.

For example, Hranitzky says, "There’s a clear difference in the mechanism of AFib in a 30-year-old marathon runner as opposed to an 80-year-old with a long-standing history of hypertension -- these differences involve not only what sustains it but what initiates it."

In the marathoner, extreme physical stress can cause changes in electrical properties within the heart, triggering episodes of AFib in athletes predisposed to the condition.

In contrast, an elderly person might develop AFib because of age-related structural changes in the heart muscle. The heart becomes less flexible, and can develop tiny scars or fibrosis that can worsen with time, especially if high blood pressure is not controlled. This fibrosis can cause atrial fibrillation.

For the marathoner, doctors aim to prevent the triggering of the arrhythmia, Hranitzky says. If the triggers can be identified -- usually they are found near the junction of the pulmonary veins and the left atrium of the heart -- the arrhythmia can often be effectively treated with antiarrhythmic medications that abate the triggers, or cured with catheter ablation.

The elderly person, however, has a more complex situation. His heart cells have undergone a process of “remodeling,” and merely eliminating the triggers does not suffice.

"We must also alter the remodeled substrate," Hranitzky says, using either drugs or ablation to target the affected heart tissue.

The researchers are now probing deeper into what makes AFib different in each person.

"Clearly there are people who have genetic predispositions to AFib," says Hranitsky, but "it’s not going to be a single gene that determines whether someone will have AFib or not."

To help untangle the complex causes of the condition, Hranitzky and his colleagues began assembling a biorepository and clinical database for arrhythmia research in 2006 -- collecting DNA, messenger RNA, and protein from consenting patients in the electrophysiology lab.

By identifying alterations in these molecules, the researchers hope to find new clues about the underlying mechanisms of atrial fibrillation. They plan to look for genetic or molecular predispositions based on gender, age, and race differences, as well as for differences in the way individuals respond to treatment. The findings could lead to better prevention strategies and more targeted treatments. Researchers at other institutions are working on these same types of studies.

"In reality it’s going to take a collaborative effort among many centers," Hranitzky says. "We’re not going to have all the answers, but personalized treatment for arrhythmias is something that we’re moving toward."

Daubert, who created and led the University of Rochester’s heart rhythm program until he returned to Duke this summer, says the range of new AFib treatment techniques and technologies introduced over the course of his career is heartening -- just a decade ago, for his patients with AFib that didn’t respond to medical therapy, he could do little more than watch their hearts quiver. He says he’s pleased to be back at his alma mater to tackle the next frontiers in atrial fibrillation.

"Coming back to head up the program that pioneered some of these ideas that have brought us this far is really an awesome opportunity. This is a team with the expertise and drive to truly make a difference in people’s lives."

This article was first published in the Fall 2009 edition of DukeMed Magazine.

Outside Influences

Mon, 23 Nov 2009 14:01:04 -0500

H. Kim Lyerly, MD, director of the Duke Comprehensive Cancer Center (left), and William Chameides, PhD, dean of Duke’s Nicholas School of the Environment.She was standing at the kitchen sink, washing dishes, just as she had dozens of times in my childhood when I had walked in with a question about something I didn’t understand.

But the question we were discussing was not one between a young mother and a curious kindergartner; it was between a 50-year-old woman whose breast cancer had been in remission for a year and her college-aged daughter who wondered what sort of fortunes might await her own body, yet to be told.

My mother was convinced that stress -- losing her father, moving to a new state -- had caused her disease, for there was no history of it in our family. I was thinking about the other tapestries of her life: the coal mining she grew up around; the chemical plants that billowed clouds of smoke and dotted the landscape of the region where we made our home for the first 16 years of my life.

Could any or all of these factors have caused her cancer? Would they one day haunt me or my children?

For most of us -- even for many researchers -- the relationships between nature and nurture remain murky.

But scientists at the Duke Cancer Institute and the Nicholas School of the Environment believe that such questions are answerable, that our lifestyles, our environments, even the possible effects of what’s stored underneath that kitchen sink, can be shrunk from imposing questions to understandable relationships, from theory to therapy, from perhaps to prevention.

The partnership is one-of-a-kind: No other institution in the country boasts such a level of collaboration between environmental and cancer researchers.

The effort began in 2005, seeded with a series of joint projects funded by Fred and Alice Stanback of Salisbury, North Carolina (who have since contributed an additional $6 million to the cause).

Over the years the initiative has grown and given rise to new research in both domains, with scientists coming together to explore questions that once ended where another discipline’s research lab began.

Researchers are visiting their neighboring schools, borrowing the proverbial cup of sugar, and getting personal -- just like the disease itself.

"You can find the big answers if you have the culture and the willingness to work together," says William Chameides, PhD, dean of the Nicholas School. "You have to be willing to say, 'Yeah, I’m going to stretch a little bit, and I’m going to get a little bit out of my element, because I see the big payoff.'"

In pinpointing our environmental enemies more precisely, the eventual payoff could indeed be huge -- and more than a little alarming.

"I have three kids: an eight-year-old, a six-year-old, and a four-year-old," says H. Kim Lyerly, MD, director of the Duke Comprehensive Cancer Center. "So there’s stuff in the backseat of the car. There are plastic drinking cups, toys, balls, and other man-made things."

To contemplate the spectrum of dyes, paints, and coatings on the endless odds and ends that we dig out from between the car seats and behind the sofa cushions, all the materials that end up on our skin or -- more likely -- in our children’s mouths, it’s easy to spin into paranoia or a sense of futility.

But the goal, says Lyerly, is not to "panic about the things we find; it’s to discover what kind of impact they have. If something is harmful, we want to know why. We want to link actual biology with detection in the environment.

"Let’s say we find a new type of molecule that causes cells to duplicate themselves uncontrollably," he explains.

"That’s a new insight that might help us understand cancer and therapies for the disease. But it’s also an insight we can give to the Nicholas School and say, 'Do you find this molecule in populations that are at greater risk based on your screening?'"

Mapping Cancer Risk

Marie Lynn Miranda, PhD and Amy Abernethy, MD are using Miranda’s mapping techniques to track cancer incidence in North CarolinaNew tools such as geospatial mapping are making these collaborations efficient for both sides. Researcher Marie Lynn Miranda, PhD, who leads the Nicholas School’s Children’s Environmental Health Initiative, has helped advance this mapping technique -- which uses a range of spatial data layers -- in North Carolina and nationally through her work on environmental contributors to maternal and child health.

Now, geospatial mapping is being expanded to other fields as well, including cancer.

The mapping tools herald an age of "personalized environmental health," paving the road to a better grasp on where cancers occur and why, says Amy Abernethy, MD, associate director for IT and informatics at the Cancer Institute, who often works with Miranda.

Using a database of Duke cancer patients, Abernethy says, researchers are compiling where patients with different kinds of tumors live and then correlating their information with geographic maps of known heavy metals or other kinds of exposures considered potential carcinogens -- arsenic, radon, and even the sun itself.

As more and more information is gathered and other databases are folded in, those maps will be not only heavy-duty tools for research, says Abernethy, but eventually clinical tools to help drive home the importance of proper screening. Like the old picture of lungs blackened from smoking, physicians can pull out a map during an office visit that details their patients’ risk based on geography.

"It allows people to see that, 'Wow, I live in Johnston County and these are the things that I need to worry about, and this is based on real-life data,'" Abernethy says. "It becomes much more meaningful.

"I think ultimately we'll become more and more sophisticated in our risk-modeling.
We'll be saying: 'This is a 33-year-old woman living in Johnston County, near Highway 242, who has lived in Wake and Durham counties at prior points in her life, and her risk of having this type of cancer by the time she turns 70 is x.' And it may influence the screening we recommend."

What’s in the Water

Avner Vengosh, PhDCancer is an intimate foe; when you have it, and even when you no longer do, reminders of its presence pockmark your body and your psyche.

And many of the environmental insults that are linked with oncogenesis, as Nicholas School professor Avner Vengosh, PhD, knows, also pockmark the landscape that surrounds us.

Vengosh is a geochemist who is known internationally for his expertise on the chemical and isotopic composition of water contaminants, developing tracers for contaminants in water supplies from the Middle East to the mountains of western North Carolina, where harmful radon in groundwater was exposed.

He has collected samples of the coal-ash waste that spilled from the Tennessee Valley Authority’s Kingston coal-burning plant on December 22, 2008, covering 300 acres of land and water with sludge and damming a tributary of the Emory River there.

Coal ash has relatively high levels of toxic elements such as radium and arsenic; long-term exposure to either has been deemed a cancer risk by the Environmental Protection Agency.

"The massive coal-ash spill contaminated associated surface water -- specifically with arsenic—but the good news is, we detected only trace amounts of arsenic in waters beyond the dammed tributary," Vengosh says.

"The data suggest that river flow has diluted the arsenic content. The river is relatively clean, but the water from areas like the dammed tributary, where the coal ash accumulated, still contains high arsenic levels."

The Tennessee coal-ash spill is a wake-up call, as about 70 million tons of coal ash are stored around the United States.

Avner and fellow Nicholas School investigators worked with Julia Kravchenko, MD, PhD, of the Cancer Institute on a paper (published in May in Environmental Science & Technology) that examines the link between environmental contaminants found in the Kingston coal ash, contaminated water, and health risks -- the first of several planned studies of the biomedical implications of environmental disasters.

Chameides is particularly interested to see what the Vengosh team finds as its research into these links unfolds during the coming year; hundreds of coal-ash retention ponds exist in the United States, he says, and if high levels of carcinogens are found in Tennessee, those data could ultimately unlock clues about cancer incidence in other areas of the country.

"If you try to understand in general the impact of environmental pollution on human health,” Chameides says, “it’s sometimes useful to look at places where you see a really high impact, a larger signal such as the coal-ash spill, and then work backward from that to see what’s happening in a more subtle way in other places."

The Hopeful Science

Duke epigenetics expert Randy Jirtle, PhDIn 2003, Duke epigenetics expert Randy Jirtle, PhD, proved that while our genome is fixed when we’re born, our epigenome -- the collection of chemical switches that tell the genes what to do -- is not.

If the genome is the hardware of our bodies, the epigenome is the reprogrammable software capable of yielding to outside influences, says Jirtle.

In his study, baby mice suffered from a flawed gene that led to increased susceptibility to obesity, diabetes, and cancer -- except among those whose mother had been fed a prenatal diet including folic acid.

In that group, the extra nutrients acted at the molecular level to latch onto the troubled gene, resulting in its appropriate regulation. Those mice were born healthy.

Jirtle reported a similar finding last year on folic acid countering the negative effects of BPA, a chemical found in many plastics.

What’s more, says Jirtle, once this good-guy methylating gang does its work in the embryo, the genomes of those mice’s offspring are permanently mended, carrying the good alteration throughout the individual’s life. It is, he says, a hopeful new way of looking at life, and at medicine.

Of course, it also means that, as more is learned about the epigenomic switches, clinicians will have to ask their patients to sidle up to the responsibility trough and get smart about their lifestyle and environment choices based on the findings.

"What you eat, what you drink, and so on can affect not only yourself, but generation upon generation after you," Jirtle says.

That is why, although researchers continue to study the effects of nutrition and lifestyle on cancer incidence, Jirtle believes doctors should urge their pregnant patients -- and women thinking of starting a family -- to start limiting their exposure to BPA now by avoiding food from cans coated in plastic and water from plastic containers made from BPA, which may mimic estrogen(s) in the body.

Along with oncologist Victoria Seewaldt, MD, Jirtle also is working with a subset of our genome called "imprinted genes" to learn more about the influence of environment on breast cancer.

Unlike other genes we’re born with, in imprinted genes, only one of the two copies inherited from the mother and the father works. This nonworking gene is epigenetically switched off, or methylated, in a normal gene. But, if either both copies or no copies are working, susceptibility to disease increases.

Jirtle estimates that only about 200 of the 25,000 genes in our makeup are imprinted, but these are the ones Jirtle believes will unlock the mysteries behind many diseases, especially cancer.

The researchers are looking at people with a high risk of breast cancer to see if there are epigenetic changes in the KCNK9 imprinted gene, a potassium channel that has been shown in previous studies to result in breast cancer when overexpressed. Jirtle says they have already seen some evidence of a relationship at the epigenetic level.

Jirtle’s studies even investigate how the environment within the body may affect the epigenome -- specifically, he’s researching the link between neurological disorders and cancer, because patients with schizophrenia are known to have low incidence of cancer.

He believes that one day, when these ties are better understood, therapies might be introduced to turn off disease-causing genes and turn on protective mechanisms at the cellular level.

"With epigenetics," he says, "for the very first time, the word prevention comes into cancer. To get to the answers, though, you have to bring together groups of people that possibly have never been brought together before; and in fact, that’s what’s happening right now between the Nicholas School and the Cancer [Institute]."

Disrupting the Status Quo

Donald McDonnell, PhDBPA is one of several known endocrine disruptors -- though it has received by far the most attention, causing certain plastic water bottles, baby bottles, and other goods to be shunned almost overnight.

But Jirtle’s colleague, Duke molecular cancer biologist Donald McDonnell, PhD, discovered startling information regarding endocrine disruptors and pharmaceuticals that should give pause to doctors prescribing medications with hormonal components.

McDonnell’s team showed why a common solvent used in industrial cleanrooms and one of the most popularly prescribed drugs in the country could lead to increased risk of cancer in some individuals.

His team tested a cleaning agent known as ethylene glycol methyl ether (EGME) that’s used in varnishes, paints, dyes, fuel additives, and the semiconductor industry; and valproic acid (Depakote), a drug with a similar chemical makeup that is prescribed for migraines, seizures, and attention deficit and bipolar disorders.

They discovered that EGME, when metabolized, and valproic acid both act as hormone sensitizers—they enhance progesterone and estrogen activity inside cells.

When that hormonal activity is accelerated in a person who is already ingesting a drug that contains synthetic progestin and estrogen (such oral contraceptives or hormone replacement therapy), the extended, double exposure of hormones in the body is likely to increase cancer risk.

McDonnell says the results are a break from more traditional thinking on the work of endocrine disruptors, where the focus has been on agents that mimic estrogen in the body rather than those that change the way cells see estrogen.

That mimicking also has been the main focus of drug testing for such disruptors, and until testing strategies take this new mechanism into account, he says, physicians need to act cautiously before prescribing any drug in combination with hormone-containing pharmaceuticals.

"This adds fuel to the debate as to the effectiveness of the currently used tests for endocrine disrupters," says McDonnell. "The drug-testing programs are outdated and do not adequately incorporate our current understanding of hormone action."

McDonnell suggests taking particular caution with tamoxifen, which is widely used in the treatment and prevention of breast cancer but is chemically altered from an antagonist to an agonist in the presence of EGME and valproic acid.

And while he has received some feedback from oncologists who do check with their patients about valproic acid use, for the most part, he says, "the message hasn’t yet hit home" in the medical community.

McDonnell adds that there’s no doubt in his mind that the environment contributes in a very significant manner to cancer susceptibility.

"Endocrine disruptors have received a lot of attention of late but there are likely to be hundred of other types of agents in the environment that impact cancer risk."

Ready for Its Close-up

Environmental effects on cancer are taking center stage in the medical research community and likely will become a greater topic of conversation around dinner tables, too.

It’s precisely that growing curiosity among the public about what’s safe around us and what isn’t that is fueling the partnership between the Nicholas School and the Cancer Institute.

Patients want answers; researchers want to give doctors the right tools to provide those answers.

In the coming months, Lyerly and Chameides will see the connections they’re making at Duke unfold nationally. The President’s Cancer Panel, a group Chameides spoke to last fall which is tasked with appraising the National Cancer Program, will focus its annual report to President Barack Obama on the links between the environment and cancer.

Lyerly and Chameides also are co-chairs of a state cancer-plan task force on the same topic, and the foundation Susan G. Komen for the Cure also will be putting a brighter spotlight this year on environmental links to breast cancer.

"When I first called Bill to get directions to his office, he told me, 'Just follow the
Birkenstocks to the Levine Center,'" Lyerly says.

Now that trail has becoming a well-beaten path -- and a road that the two hope others may follow.

"The more we work with the School of the Environment, the more we understand that there are few people at the Cancer Institute who couldn’t find ways to interact with their expertise," says Lyerly. "We’re hoping this will be a model for other places, for balancing individual research accomplishments with the collective good.

"We can find the answers if we work together."

This article was first published in the Fall 2009 edition of DukeMed Magazine.

Sound Plans

Tue, 24 Feb 2009 16:33:35 -0500

Rachael Ragin was 45 years old before she knew that fizzy soda bubbles make noise.

Profoundly hearing-impaired from infancy, Ragin, of Cary, North Carolina, successfully navigated the hearing world for years with the help of two powerful hearing aids, despite being able to understand only 8 percent of the words spoken in a soundproof auditory booth. But when she entered college, her hearing deficit became increasingly difficult to overcome.

“My hearing was so bad that in addition to wearing hearing aids, I learned sign language and started relying on an interpreter,” which she did for the next two and half decades, Ragin says.

The mother of two was in her early 40s when she began investigating cochlear implants, the only auditory prosthetic devices proven effective for treating severe hearing impairment and deafness.

Debara L. Tucci, MD, MS

In 2003, Ragin underwent cochlear implant surgery, performed by Duke neurotologist Debara L. Tucci, MD. Within several weeks, Ragin’s hearing comprehension had soared to 95 percent.

“The world became magical with all the sounds it made,” Ragin says. “Being able to better communicate with my family, hearing the wind in the trees, listening
to rain fall…it was thrilling.”

While Ragin says the decision to use auditory prostheses is a personal one -- and that she, like many of the two million Americans who are deaf or profoundly hard of hearing, continues to take great pride in deaf culture -- she is delighted to have opted for cochlear implantation.

“I live and work in a hearing world,” says Ragin, a doctoral-level consultant who works with deaf and hearing-impaired children for the North Carolina Department of Public Instruction. “My implants allow me to negotiate that world as well as I do the deaf world.”

A Flat Miracle

The cochlear implant is arguably the most significant advance to date in the treatment of hearing loss -- a widespread condition that the World Health Organization consistently ranks among the top 15 medical concerns in terms of human suffering and economic cost.

In the United States, about 10 percent of the population is deaf or hard of hearing, with some 28 million people -- about half of them aged 65 and older -- experiencing hearing loss significant enough to impact their quality of life.

“Thirty years ago, there were no options, simply no treatments, for someone who was deaf or had a severe hearing loss,” says Duke-trained electrical engineer Blake S. Wilson, an adjunct professor in otolaryngology who also serves as the chief strategy advisor for MED-EL GmbH of Innsbruck, Austria, a leading developer and manufacturer of cochlear implants.

Wilson has been associated with Duke otolaryngology since 1984, when he and Duke otolaryngology chief emeritus Joseph C. Farmer Jr., MD, established the Duke Cochlear Implant Program as one of the nation’s first. Tucci has led the program since coming to Duke in 1993.

“Cochlear implants have enabled us to come a very long way in a relatively short time in terms of treating profound hearing loss,” says Wilson. “Most of today’s implanted patients can understand everyday speech with hearing alone, without lip reading -- many in noisy environments, some even on the telephone. To me, that’s a flat miracle.”

While technological advances have opened a new world of sound for many, a host of challenges remains. Not everyone with hearing loss is a candidate for cochlear implants, and outcomes vary widely among recipients -- for reasons that aren’t fully understood. And for many millions of children and adults worldwide, affording or even accessing the technology remains out of the question.

Not all people with profound hearing loss consider it a disability; many people who were born deaf or severely hard of hearing -- or who became so early in life -- find deep fulfillment and great pride in deaf culture. But for many others with untreatable or undertreated hearing loss, the economic and emotional costs can be enormous.

For those who became deaf before they learned to speak, experts estimate a lifetime cost of more than $1 million per person to address hearing-related challenges. Many of these people say their hearing deficit makes them feel disconnected, socially isolated, and discriminated against.

On January 29, Duke’s efforts to help these individuals were galvanized in a new way with the official launch of the Duke Hearing Center. This major interdisciplinary initiative is designed to harness Duke’s scientific and clinical strengths to alleviate the massive global toll of hearing loss.

Synthesizing the Science

Part of the plan for the new center, says Wilson, is to take advantage of an “explosion of knowledge” that’s occurred in the fields of otology, neurotology, and engineering, particularly in the past 10 years.

“Duke has awesome resources and capabilities across the spectrum needed to develop new treatments for hearing loss, and we’re highly unusual in that respect,” Wilson says. “The combination of all these capabilities is what’s so powerful, and a large part of the rationale for the hearing center is to bring that strength to bear on such an important societal problem as hearing loss.”

Co-directed by Tucci and Wilson, both of the Department of Surgery’s Division of Otolaryngology-Head and Neck Surgery (OHNS), the center will foster collaborations among faculty within the School of Medicine, the Pratt School of Engineering, the Duke Center for Cognitive Neuroscience, the Division of Neurology, the Duke Global Health Institute, and the Duke Institute for Genome Sciences & Policy.

Nancy Andrews, MD, PhD“It’s very important for investigators at Duke to work on solving problems that have a major patient impact, and the center’s multidisciplinary approach will be critical to this effort,” says Nancy Andrews, MD, PhD, vice chancellor for academic affairs and School of Medicine dean, who granted the program “center” status in July.

Andrews herself has a personal interest in otology, and recently made a serendipitous discovery of a gene in mice that may play a role in determining how genes are expressed in developing inner-ear cells in humans.

“Hearing loss is a large problem, but it’s one for which we have real hope that modern science will lead to solutions,” she says. “Many causes of hearing impairment are preventable, and understanding those will help in the short term. In the long run, scientific investigation will eventually help people preserve their hearing.”

For example, says Wilson, “about 60 percent of congenital hearing loss is caused by genetic defects, and there’s huge potential to identify additional defects that lead to hearing loss and develop molecular repairs for them.”

Another area of investigation the center plans to pursue is cellular-regeneration therapies, which take a cue from the animal kingdom -- some aquatic animals and birds regenerate their damaged inner-ear receptor cells with the help of nearby cells that act as stem cells.

“We hope to build upon a rapidly growing body of knowledge to better understand the biology of the mammalian inner ear, with the goal of inducing hair-cell and neural regeneration and thereby restoring hearing,” Tucci says. “This field of cell biology holds great promise for the treatment of sensorineural hearing loss, for which there is no direct treatment at present.”

Improving the Implant

In addition to pursuing basic-science and translational research, center faculty will work to improve existing treatments for hearing loss, including the groundbreaking cochlear implant.

Much of this work will build upon a longtime collaboration between OHNS and the Research Triangle Institute (RTI) Center for Auditory Prosthesis Research -- which Wilson, who is internationally recognized for inventing many implant components, led from 1994 to 2002.

This partnership has produced a number of breakthroughs in cochlear implant design, as well as the signal- and speech-processing strategies used in cochlear implants, hearing aids, and other devices used to improve hearing.

More than 130,000 people worldwide have received cochlear implants since they became widely available in the early 1980s -- and thanks to constant improvements in the devices, many more people now stand to benefit from them than ever before. In fact, says Tucci, “In our state alone, many, many people are candidates and don’t know it.”

Many insurers now cover at least one implant -- including Medicare and, for children, Medicaid -- and there are no real age restrictions for getting them, she adds. Although about a third of the division’s patients are children from one to 18 years old, “we’ve implanted patients as old as 86 who have done very well,” Tucci says.

However, Wilson points out, there’s still much work to be done to help cochlear implantation reach its true potential -- and transform the lives of even more deaf and hearing-impaired people.

Unlike hearing aids, which amplify sound so it is loud enough for damaged ears to hear it, cochlear implants reroute sound around damaged parts of the ear, directly to the auditory nerve, which stimulates the area of the brain that receives and makes sense of auditory input.

At present, the best candidates for cochlear implants are young children and people whose auditory brains have received at least some ongoing stimulation -- such as those who regularly wear hearing aids. That’s because connections among neurons and auditory pathways erode as the brain is deprived of input, and it’s easier to successfully establish or re-establish ear-brain connections when they haven’t been idle for a prolonged period.

Hearing Center researchers will explore ways to overcome that obstacle, and also address the differences in outcomes among recipients, which Wilson says are still not completely understood.

“A leading theory [as to why implants work better for some people than others] is that it’s due to individual differences in auditory brain function,” which can vary widely among people who have suffered from different degrees of hearing loss for different lengths of time.

“The brain is the tail that wags the dog in determining cochlear implant outcomes,” he says, “and we need to figure out why and what we can do about it.”

Because hearing-impaired people who are not candidates for cochlear implantation can benefit significantly from other devices, Hearing Center faculty will also work to improve auditory prostheses across the board, says Wilson. These devices include hearing aids and the hearing aid-cochlear implant hybrid -- both for people with some residual hearing -- as well as the central auditory implant (CAI), a device, still in the early stages of development, that is designed to stimulate brain structures central to the auditory nerve.

Addressing a Global Crisis -- At Home and Abroad

To speed the delivery of these advances in technology and research to the people who need them, Duke Hearing Center faculty plan to grow a statewide network of sites for clinical trials and patient care.

“One of our overarching goals is to integrate clinical research with treatment,” says Tucci, who is currently working with David L. Witsell, MD, director of the Duke Voice Care Center, on an NIH grant to develop a network of clinical research sites within academic centers and community-based private practices.

“The idea is to see which interventions work best in treating patients with otologic disease -- and for the Duke Hearing Center to have a presence in most North Carolina communities in the next five to 10 years.”

But the Hearing Center’s vision extends far beyond North Carolina. Tucci explains that the center’s mission includes fighting hearing impairment globally, where it may be an even greater problem than in the United States.

Roughly 60 million people in India suffer from significant impairments in hearing, for example, many due to congenital rubella -- which is preventable by vaccination. And in China, more than seven million people are completely deaf, an incidence due largely to widespread use of ototoxic over-the-counter antibiotics administered by the “barefoot doctors” during the country’s cultural revolution.

As part of a partnership between the Department of Surgery’s Global Health Initiative and the Duke Global Health Institute, Tucci and Wilson have traveled to India to investigate opportunities for clinical outreach and research collaboration. They also are working with Samuel L. Katz, MD, internationally known chairman emeritus of the Duke Department of Pediatrics, to create an infrastructure to prevent and treat hearing loss in India.

“We’re working with [our counterparts] there to establish rubella vaccine and hearing screening programs, to facilitate the care people need, and to make low-cost cochlear implants accessible to patients who are candidates for them,” Tucci says.

Whether it affects a child in an impoverished nation, a middle-aged American professional, or Grandma, smiling as her family shares stories around the holiday dinner table, not hearing a word, “hearing loss can be isolating and tragic, and that’s the real impetus for creating the Duke Hearing Center,” Tucci adds.

“By bringing together researchers in many areas related to hearing science and hearing health care and working to broaden our clinical outreach in the community, in the U.S., and globally, we will be able to make a tremendous difference in many people’s lives.”

Rachael Ragin is living proof of that. “Sound and communication are at the core of human society, and people with profound hearing loss often struggle to be a part of that -- particularly children, who rely on effective communication to learn,” Ragin says. “I truly believe that efforts to reduce the prevalence and the impact of hearing loss are efforts to diminish a serious human-rights concern.”

To learn more about the Duke Hearing Center, visit hearing.surgery.duke.edu and dukehealth.org/hearingcenter.

To make a referral, call the Duke Consultation and Referral Center at 1-800-MED-DUKE (1-800-633-3853).

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Rationing Health Care: Why We Shouldn't Always Get What We Need

Mon, 16 Nov 2009 13:26:06 -0500

Gopal Sreenivasan, PhDHealth care reform has been debated for decades, but an ailing economy, aging population, and new administration are bringing a renewed sense of urgency to the discussion of how to manage the costs and provision of health care in the United States.

Bioethicist Gopal Sreenivasan, PhD, asserts that a seemingly severe approach -- rationing -- is not only part of a workable solution, but a moral duty.

Most people believe that health care systems should ideally provide citizens who are sick with whatever health-related goods and services they need. While this model may appear at first glance to be the equitable way to meet people’s health care needs, it is not really morally defensible on a national scale.

This is because a nation’s health is not the only important good with a claim to the finite pool of social resources -- there are also education, defense, transportation, and infrastructure, to name just a few others.

The more society allocates to health-related goods and services, the less it can allocate to anything else.

In other words, when access to every medically necessary good and service leads to overspending on health care, a country is forced to underspend on schools, roads, and other critical services. This is incompatible with justice, which forbids robbing Peter to pay Paul.

Countries are therefore morally obligated to observe a strict limit on health care spending. In effect, they must fix a ceiling on their annual health care budgets before knowing the total cost of the medically necessary care required by their population over the year.

By supporting this approach, a nation commits itself to rationing the health care goods and services it provides its citizens.

Building the Case for Rationing

Since rationing means that citizens will be denied some medically necessary care, people are often understandably uncomfortable with this notion. Most don't want to say it's acceptable to withhold health care benefits or to settle for anything less than what is, at least in principle, possible.

It seems uncompassionate, even unfair.

Still, the evidence is clear and mounting that we must set limits on health care expenditures. Already, the United States spends more on health care -- both absolutely and as a percentage of the gross domestic product (GDP) -- than nearly every other country by far.

Even worse, in America, the growth rate of medical spending has consistently surpassed the growth rate of the GDP in recent years.

In fact, the share of the GDP the U.S. spends on health care -- about 16 percent -- is projected to reach nearly 20 percent by 2017. (The average for countries in the Organisation for Economic Co-operation and Development is 9 percent.)

When the percentage of GDP spent on health is rising, that means that health care spending is gobbling up resources that were previously spent on other goods. As long as the growth rate in health care spending outstrips the growth rate in GDP itself, this diversion of resources from other legitimate expenditures only gets worse.

At current growth rates, health care spending will eventually cross the line into claiming resources that should be spent on other goods, no matter where you draw that line. Since it is difficult to defend a more-than-15-percent share of GDP designated for health care, that line may have already been crossed.

Of course, it's hard to suppress the thought that if only we could eliminate all the waste and inefficiency in the health care system, we really could have it all -- and not have to settle for rationing medically necessary services.

Yet while every little bit helps, it's highly unlikely that improving efficiency and eradicating waste would allow us to cover everything, as the "Growth in national health expenditures under various scenarios" chart makes clear.

The three lines represent projections of health spending under different assumptions about possible cost savings. The top line (baseline national health expenditures) projects current growth trends without any cost savings. The "one-time savings scenario" assumes significant initial savings (e.g., from eliminating waste), but no change in the underlying growth trend. The "slowing trend scenario" assumes the reverse: no significant initial savings, but a smaller underlying growth rate.

Even the best-case scenario (slowing trend) has health care spending almost doubling between 2005 and 2015. That is because new technology, rather than waste or inefficiency, is the fundamental driver of growth in health care spending.

Asking the Tough Questions

But how do we decide where to cut costs? The first step is to establish a firm limit on health care spending that is independent of (and less than) what is technically possible to spend on health care, even when spending is restricted to medically necessary services and all waste is eliminated.

However, this does mean accepting that some medically necessary and beneficial services will not be covered, because we cannot reasonably afford it.

The next step is to develop adequate measures of the comparative cost and effectiveness of different effective medical interventions. The goal would be to have a rational and accountable method of deciding which interventions are most worthwhile to cover with a limited budget and which ones, regrettably, must be left out. But this is another topic for another day.

The questions of how to ration health care, and how much care we as a country can reasonably afford to pay for, will not be easy to answer. But accepting rationing as a necessary and moral approach remains the first step toward resolving those questions -- and creating a more just health care system.

Gopal Sreenivasan, PhD, is the Lester Crown University Professor of Ethics and a professor of philosophy in Duke's Trent Center for Bioethics, Humanities, and History of Medicine. His research in bioethics largely focuses on the broad notions of health and justice.

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Robots in the OR

Mon, 16 Nov 2009 14:53:12 -0500

Urogynecologist Anthony Visco, MD, readies a robot for surgery.When he decided to become a surgeon, Anthony Visco, MD, entered one of the most hands-on of professions. But nowadays he does some of his best work when sitting eight feet away from his patient.

To repair pelvic prolapse, for instance, the gynecologic surgeon begins by making dime-sized incisions in the patient's abdomen, through which four hollow instruments called trocars are placed.

He then steers a state-of-the-art surgical robot over to the patient's belly. The robot's four arms are docked -- attached to the trocars -- and then used to insert a camera and specialized robotic instruments such as forceps, scissors, a scalpel, or a needle holder into the patient's body.

Sitting at the robot console, Visco operates the instruments and camera using hand controls and foot pedals. His face rests in a viewer with left and right eyepieces. The views from the robot's two cameras merge to give a three-dimensional view of the operating field that rivals that of open surgery.

"You can zoom in closer than you can with your own eyes," Visco says.

As for the arms, there's little comparison -- the robotic instruments can rotate much like the human hand, but with a greater range of motion and on a much smaller scale, enabling doctors to perform intricate maneuvers through keyhole incisions.

Engineered for dexterity, surgical robots have opened up new possibilities in the OR since they arrived on the scene less than a decade ago -- enabling surgeons to give patients a minimally invasive option for some of the most complex procedures.

Currently only one robotic surgical system is sold commercially in the United States, Intuitive Surgical's da Vinci Surgical System, which was approved by the Food and Drug Administration for use in general surgery in 2000. Since then it's been approved for a variety of cardiac, thoracic, urologic, and gynecologic procedures.

Urology and gynecology appear to be the biggest users of robotics; a 2008 financial filing from the company notes that robotic prostatectomies and hysterectomies make up 79 percent of the procedures performed with its system.

David M. Albala, MDFormer urologic surgeon David Albala, MD, says that data from the company show that in 2007, over 60 percent of prostatectomies in the United States were performed using the robot, up from some 40 percent in 2006.

Robotic surgery has been steadily gaining ground at Duke, too. Since the medical center acquired its first robot in 2002, hundreds of patients have come here from around the state and the country to have robotic surgeries.

Today Duke doctors have the most experience in North Carolina in robotic prostatectomies and the most experience in the world in robotic sacrocolpopexy (the procedure to repair pelvic prolapse).

But surgeons point out that while calling such procedures "robotic surgery" may sound cutting-edge, in truth they are robotically assisted; the robotic arms are just extensions of the surgeon's hands.

"Robotics isn't going to take a mediocre surgeon and make him a great surgeon," says Visco, chief of the division of urogynecology in the Department of Obstetrics and Gynecology.

The field has its critics, too; some surgeons at Duke say that robotics simply isn't for them.

But there's no denying that robotics is making a major impact on the surgical scene -- and at Duke, proponents and skeptics alike are leading efforts to define just what its place should be.

Writing the Book on Sacrocolpopexy

Developed at Duke in the 1960s, sacrocolpopexy, in which a mesh is attached from the vagina to the sacrum, is considered the gold standard for repair of pelvic prolapse -- a sagging of the pelvic floor tissues which can happen after menopause, childbirth, or a hysterectomy.

One of the procedure's progenitors taught it to Visco during his urogynecology fellowship at Duke in the late 1990s; Visco first learned to perform the open surgery, then the laparoscopic technique -- in which surgery is performed through small incisions using specially designed handheld instruments.

"I did a lot of open colpopexies. I believed in minimally invasive surgery. When I was exposed to the robot, it seemed like an obvious extension of what I was already doing," he says.

Now he has literally written the book on performing them robotically -- he authored the colpopexy training manual for the da Vinci system, regularly hosts courses at Duke, and provides live broadcasting of the surgery, so that surgeons and urogynecologists around the country can learn about the technique.

Visco expects the need for sacrocolpopexy to increase as the baby boomers age. And he now considers robotics the gold standard for performing that surgery in a minimally invasive way.

Because colpopexy requires intricate steps such as attaching mesh, the laparoscopic version is just too hard for many surgeons to learn. "There are a limited number of people who can actually perform a laparoscopic colpopexy," Visco says.

Tying knots and suturing is difficult with laparoscopic instruments because they're straight "like a pair of long, skinny needle-nose pliers," Visco says. And they don't bend. Urologic surgeon David Albala, MD, likens using laparoscopic instruments to operating with a pair of chopsticks.

Visco and colleagues have documented that robotic colpopexy does provide the short-term benefits that patients are looking for. They found that compared with the open procedure, robotic sacrocolpopexies provided similar short-term surgical outcomes, but the robotic group had significantly shorter hospital stays (1.3 days on average versus 2.7 days for open), and their blood loss was significantly less (103 ml versus 255 ml).

Duke owns four different robots, two at Duke University Hospital and one each at Duke Raleigh and Durham Regional hospitals, which are used to perform a variety of procedures.

Like Anthony Visco, Duke urogynecologists Alison Weidner, MD, and Jennifer Wu, MD, perform robotic sacrocolpopexy and other robot-assisted procedures, while Cindy Amundsen, MD, offers other minimally invasive options for the treatment of pelvic prolapse.

Gynecologic oncology surgeon Fidel Valea, MD, uses the robot mostly for radical hysterectomy, which requires a lot of dissection. Craig Sobolewski, MD, chief of the Division of Minimally Invasive Gynecologic Surgery, uses the robot mostly for myomectomy (fibroid removal), which involves a lot of suturing.

"If the surgeon is performing intricate steps of a procedure such as tying multiple sutures, the robot is much more capable of mimicking what we do with open surgery. For me, that makes the robot the perfect choice for laparoscopic removal of fibroids,"
Sobolewski says.

Since he mastered the laparoscopic version years ago, Sobolewski doesn't do straightforward hysterectomies robotically and reserves the robot for more complex procedures. As all these surgeons point out, they don't dabble; for each procedure, most of them pick one method, then perfect it.

In urology, Albala performs nearly all of his radical prostatectomies robotically. Other surgeons who offer the robotic procedure are Phil Walther, MD, Thomas Polascik, MD, Cary Robertson, MD, and Brant Inman, MD.

Combined, these Duke surgeons now perform 300 to 350 robotic prostatectomies per year. Albala trains urologists from across the country in the procedure, helping to disseminate the new approach even more widely.

Climbing the learning curve

All these seasoned surgeons learned robotics in the midst of their careers, most using a training robot. The magnified view took some getting used to. So did keeping all three robotic instruments in view at all times.

"If you can't see one of them, and your hands are in the cradles, you could make it do something you don't want it to," Valea says. Then it's a matter of practice to get familiar with the power and sensitivity of the controls, and to learn to take full advantage of the wristed instruments.

When Visco was in medical school, he would take suture material home and put stitches in his scrubs, to practice tying knots. He and colleagues did the same type of practice with the robotic instruments.

Visco also videotaped his first robotic cases and spent time reviewing them, to find places where he could have tied a knot or made a cut more efficiently.

Though Albala's first few robotic prostatectomies took seven or eight hours, his speed increased as he got his bearings in the magnified view of the operating field. "Now, I feel like I'm in total control during the case. I know my landmarks. Once you learn how the robot moves, I think the surgery is simplified," he says.

Surgeons seem to like the increased autonomy of the console; if they want to cauterize something, often they don't ask an assistant, they just press a foot pedal. And the 3-D, close-up visualization of the surgical field is considered by some to be better than they can get with their own eyes.

"It's almost as if I've stepped inside the patient," Albala says.

First a dry lab, then you fly

When the two robots at Duke University Hospital aren't in surgery, they reside in a hallway outside the operating room.

There, residents use petri dishes of coins and multicolored dollops of silicone to conduct their "dry lab" with the robotic instruments. Valea, who directs the Residency Program in Obstetrics and Gynecology, puts some of the residents through their paces.

"I may tell them, pick up this coin, turn it over, put it in your other [robotic] hand, turn it over again," Valea says. "That's a great exercise because it teaches them transfer and it teaches them rotation of the hand." They'll also practice stitching the silicone dollops together.

In the OB-GYN residency, robotics isn't yet required, but most residents are proactive about learning it, Valea says. They learn to do robotic hysterectomies, myomectomies, and pelvic floor reconstruction.

They take it in small steps, observing or assisting in surgeries first, then, when they've shown proficiency in dry lab, performing part of an operation, such as sewing up the vaginal cuff after a hysterectomy. Once they've shown they can "fly," they move on to perform other parts and then a whole operation under supervision.

"We're not putting first-year residents in there. They will have done the case open many times before they try it on the robot," Valea says.

He doesn't set a certain number of cases as a criterion for moving on; each resident's competency is judged by the faculty, and that is how he or she is deemed proficient. He notes that's a trend in surgical training in general -- using competency-based measures.

In urology, Albala uses a formal procedure to teach robotic prostatectomies. Residents assist a senior surgeon for 10 cases before actually working at the robot console.

For training purposes, the procedure is divided into three parts. Trainees first perform the third part of the procedure, which consists mostly of suturing, for 10 cases or until they become proficient. Then they do the second part of the procedure for 10 more cases, and only then do they take on the responsibility of performing two or more parts of the operation.

"It's very regimented, and I'm in the room monitoring," Albala says.

In a study published April 2008 in the journal Urology, Albala and colleagues found that outcomes -- blood loss and rate of positive margins -- for 383 patients at Duke were the same whether the experienced surgeon performed the robotic prostatectomy or the resident performed it.

"One of the things we're very proud of at Duke is we've trained 16 different surgeons in urology at this point in how to do robotics safely and with good outcomes," Albala says.

Are the benefits overhyped?

Judd W. Moul, MDLike most of these surgeons, Judd Moul, MD, chief of the Division of Urology in the Department of Surgery, sees robotics as part of a trend toward minimally invasive procedures that will only keep growing.

But he expresses concern that some hospitals acquire robots just to keep up with the Joneses, and others hype them so much that some patients think the robot is more than what it really is -- a tool that needs the skill of a surgeon.

In a study published October 2008 in European Urology, Moul and Albala found that patients who underwent robotic-assisted prostatectomy were more likely to report being regretful and dissatisfied, possibly because they had higher expectations that they were receiving an innovative procedure.

The study points to the need for doctors to make sure patients know all the risks and benefits of the procedures they may choose, Moul says. For radical prostatectomy in particular, Moul wants to see more data to show that robotics is superior to open surgery.

For both procedures, the rate of complications, such as incontinence or sexual dysfunction, is the same. The smaller incisions possible with the robot do result in less blood loss, but at Duke it's not enough to cause a difference in transfusion rates, he says.

Moul also points out that the incisions made for the robot are in the abdomen, higher on the body than the incision for an open prostatectomy.

"It's important for patients to understand that the robotic prostatectomy is going through a cavity that wouldn't normally be entered for this surgery," Moul says. "Open surgery stays below the intestines, so there's a slightly lower chance of intestinal injury."

Albala counters that studies from other institutions find that patients who have the robotic procedure show decreased blood loss, decreased transfusion rates, shorter hospitalization, decreased pain, and decreased analgesia use when compared to patients undergoing open procedures.

"It's an evolving field," he says. "There are over a thousand robots in use now, and groups around the world are constantly improving the outcomes. We're continually modifying our practice based on new evidence in the literature."

And he thinks that patients will drive increased demand for robotics. "With a robotic prostatectomy, the patient will leave the hospital the next day. The catheter will stay in place for about a week to 10 days. The patients like that," he says.

Even Moul says the use of the robot has inspired him and other urologic surgeons to refine procedures. "We're a competitive bunch. When the robotic guys came in and said 'We can get patients discharged on day one,' we open guys changed our techniques. We started using long-acting local anesthesia in the incision and tweaked this and tweaked that, and said 'Okay, now we can get our patients out on post-op day one.' It's pushed us to reassess our whole practice pattern for radical prostatectomy and try to do a better job for all patients."

Such efficiency translates into the intangible benefit of a calmer operating room. As with standard surgeries, the robotic operating team is honed so that everyone has a defined role to execute.

"Even though the robot affords a lot of autonomy to the console surgeon performing the operation, it really is a team approach," Visco says. "We owe a lot to the nurses and the OR and anesthesia staff. We've become very efficient at setting up the robot, for example. You need a group of people who are really committed."

Adds Albala, "Duke is one of the few places where everyone in the OR, from the anesthesiologist to the nursing staff, is dedicated to robotic procedures -- so patients are benefiting from having not just an experienced surgeon, but an experienced team."

A Robot for Every OR?

Visco predicts that more and more doctors will adopt robotics because it provides a minimally invasive tool for surgeons who find laparoscopy too difficult. Laparoscopy has been around for more than 20 years, but Visco, Wu, and colleagues reviewed 2003 data showing that only 11 percent of hysterectomies in the United States were performed laparoscopically.

"I think robotics is going to allow minimally invasive surgery to be an option for a greater number of patients," he says. But will robotics completely replace traditional laparoscopy? Duke surgeons aren't sure.

Valea thinks that laparoscopy will remain very popular as the current generation of surgeons with advanced laparoscopic training enters the field. "We're infusing graduates from our training programs who are truly capable of performing advanced laparoscopy," he says.

He also predicts that the cost of the robot (more than $1 million to purchase, plus $100,000 or more in yearly upkeep costs) will prevent it from becoming an everyday tool. "I think hospitals will reserve it for the most technically challenging cases. Otherwise you will need more robots, and that will just drive the cost of medical care even higher," he says.

Open surgery will probably always be around, for several reasons.

Some patients, because of weight or prior complications in the abdomen, aren't eligible for robotic surgery -- although, Albala notes, as surgeons gain experience, they are able to offer the procedure to more and more such patients.

And some hospitals don't have the volume of cases needed to make the expense of the robot worthwhile and to enable their surgeons to become proficient at robotics, Albala says. It takes 25 robotic cases to get really comfortable and maybe 250 to become a master, but a surgeon at a community hospital may perform only 10 prostatectomies a year.

"Many community-based urologists refer patients to us for robotic surgery, and then we transfer them back for follow-up care," says Albala. "Since we were the first in the state to offer robotic prostatectomies, we've been able to build strong relationships with community physicians across the region, and we're grateful for that."

Visco thinks the ideal way to grow robotics is the same way he and his colleagues have perfected their skill with it -- purposefully and carefully. "I think there is probably a pressure to offer this kind of new technique for patients," he says.

"But we still want to do the fundamental things -- take care of patients, get them home in a reasonable period of time, have few complications if any, and give them good long-term outcomes. "If we can do that with a minimally invasive approach? Great."

Note of disclosure: Visco consults for Intuitive Surgical, manufacturer of the da Vinci Surgical System.

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Finding Freedom from Back Pain

Thu, 10 Jul 2008 08:33:54 -0400

When patients talk to Paul Tawney, MD, about their aching backs, they can be sure he knows the lay of the land.

His own journey with back pain began in college, when he was in the gym lifting 365 pounds.

"My foot slipped about half an inch, and I felt pain in my back, the back of my thigh, and my calf," says Tawney, assistant professor of orthopaedic surgery at Duke.

"I put the weight down and I passed out."

Doctors told him he was fine neurologically, but later, his foot started giving way whenever he'd get out of his car.

Imaging studies showed that Tawney had a ruptured disc and previously undiagnosed congenital spinal stenosis (narrowing of the spinal canal). Surgery to remove the disc and correct the stenosis helped, but didn't heal all. Tawney's back has gone out several times, including while he completed a surgery rotation in medical school. During a marathon operating room session, Tawney spent hours with his arms in one position, holding up a retractor.

"I twisted to wheel the patient out of the operating room, and that was it," he says. He was bent over for days.

Tawney decided the physical demands of being a surgeon were too much for his back.

"So I researched a bunch of different medical specialties and found the field of physical medicine and rehab," he says.

Today Tawney still has flare-ups but controls them mostly with exercise.

"I feel it's most under control when I'm staying on top of my workouts, running as well as keeping my core muscles strong," he says.

As Tawney's experience shows, no single treatment, not even surgery, is a cure-all for back pain. And if you haven't yet had your own experience with it, chances are you will. Eighty to 90 percent of adults will have at least one episode that limits their activity for at least 24 hours.

The good news is that it will be brief -- most of us will return to normal within six to eight weeks, no matter what the treatment. But we spend a lot of money on the problem. According to a 2004 Duke study, patients with back trouble rack up over $90 billion in health care expenses annually, with approximately $26 billion of that directly attributable to treating the pain.

A 1991 study from researchers at the University of Vermont showed that most of the money is spent on those few who have chronic back pain (that which lasts for more than three months).

"Part of the art of taking care of people with back pain is identifying that small group of people who may have something truly, seriously wrong.

"And for the group of folks who have traditional back pain, it's helping them to be as comfortable and functional as possible while they're recovering, while at the same time trying to not inappropriately use health care resources," says Joe Minchew, MD, associate professor of orthopaedic surgery.

Duke's physical medicine doctors, orthopaedists, physical therapists, anesthesiologists, and neurosurgeons work together to guide people through back trouble. For most patients, the focus is temporarily relieving pain so they can get moving -- and healing. Patients with chronic, hard-to-treat pain can get advanced pain therapies at Duke that are available at few other places.

And for the few conditions that respond well to surgery, Duke offers traditional procedures as well as minimally invasive ones that can get patients out of the hospital in just a few days.

Pictures Don't Always Show the Way

Tracing the spine's parts, it's easy to see why they're vulnerable to wear. Each of the 33 vertebrae has two joints, one on each side. Just like your hip or knee, these facet joints can develop arthritis. Or the vertebrae can enlarge over time, which narrows the spinal canal and puts pressure on nearby nerves (spinal stenosis).

The discs that cushion the space between each vertebra can age too. They're made of a tough outer coating and an inner jelly-like material that can take in and release water. But over time the disc loses some of that ability to absorb water, so it doesn't cushion so well anymore. And as a disc wears, it can bulge like a lip bruised from a punch, putting pressure on spinal cord nerves and causing pain, says Winston Parris, MD, director of Duke's Pain Clinic.

All the fancily named back problems -- facet joint disease, spinal stenosis, disc degeneration -- are not really diseases, but a normal part of aging, Minchew says.

If people were randomly given an MRI at age 25, a quarter of them would show aging-related changes in their discs. By age 65, 85 percent of people would show changes in their spine that a radiologist would label "not normal," Minchew says.

If an MRI shows such changes, but your pain doesn't come from that particular area, then your "disease" probably isn't what's causing your pain.

"Nine times out of 10 you cannot look at an x-ray or an MRI or any other test and tell the patient with any absolute certainty why they're having back pain," Minchew says.

William Richardson, MD, professor of orthopaedic surgery, says that in their first weeks of back pain, most people don't even need an x-ray.

"Imaging is not indicated in the first six weeks of pain unless you have some suggestions that the person has had trauma, has a fever suggesting infection, has a major neurologic deficit, or has any history of a tumor or suggestive of a tumor, such as weight loss," he says.

Studies show that 70 percent of people get better in the first six weeks, and 90 percent in the first 12 weeks, he says.

Because imaging can be inconclusive, the dialogue between doctor and patient can be just as important as an x-ray or an MRI. In many cases, non-operative doctors steer patients toward using medications and adjunctive treatments that will relieve the pain enough that patients can do the physical therapy that will help the body heal itself.

Physical Therapy Paves the Road to Healing

While physical activity may seem daunting to someone whose back twinges or throbs with every movement, doing appropriate exercises as soon as possible can be very effective.

"We try to enable the patient to achieve early success," says Matt Roman, PT, practice manager for Duke Physical Therapy. "We tend to have people do a very high frequency of activity, but at low intensity, so they're not provoking symptoms."

Physical therapy eases back pain in three major ways.

Low-impact aerobic activity promotes fresh blood flow to the tissues and flushes out waste products. Strengthening core muscles such as the abdominals builds a strong foundation for the spine. And flexibility exercises help people go about their days without stressing their backs.

"If you bend over to reach a box, and your leg muscles aren't flexible enough to allow you to get there, the motion will occur through your spine where it shouldn't," Roman says.

Duke physical therapy researchers are working to fine-tune such interventions; researcher Chad Cook, PT, PhD, and colleague Adam Goode, PT, DPT, are testing a new scale that measures the outcomes of various physical therapy interventions for lumbar and cervical spine pain, in terms of how well these tactics improve patients' ability to go about their daily activities with ease.

Karyn Rahn, MD, an occupational medicine physician in the Department of Orthopaedic Surgery, says that physical therapy is as important as medication in treating back pain.

In fact, she says exercise therapy proved to be the magic ingredient for her patient Donald Hendrix, 79.

Because spinal stenosis made it painful to walk, Hendrix was using a walker all the time, and, for longer distances -- such as when he came for appointments at Duke -- a wheelchair.

In addition to spinal injections, Rahn suggested water therapy.

"I said, 'Look, water takes the weight away, you can work your body out and not put that pressure on your spine,'" Rahn says.

Now, Hendrix spends an hour in the pool each day doing back exercises, and another 30 minutes walking in the pool for aerobic benefit. He says he feels the best just after exercising.

"I felt so good last Tuesday, I got the lawnmower out and cut the grass, edged the yard, and blew the clippings off the driveway," he says.

Hendrix no longer needs a wheelchair or a walker.

"I've come a long way, thanks to Dr. Rahn and her encouragement," he says. Gloria Liu, MD, assistant professor of orthopaedic surgery, also emphasizes getting active early, before patients start to lose balance and sensation.

"I'm a rehab doctor," Liu says. "I want to help people get their lives back."

She also offers adjunctive therapies to ease pain, including acupuncture (two 2005 studies showed that acupuncture is moderately effective against chronic lower back pain).

Liu, Tawney, and others offer a variety of spinal injections to reduce inflammation and pain.

"If you can manage a patient with medications and physical therapy, then you don't really need to do an injection. But if they're still uncomfortable, and you want to try and calm down the nerve, then an injection is a reasonable thing to offer," Tawney says.

For patients with disc herniation or stenosis, epidural injections send steroids or anesthetic (or a combination) into the entire space around the spinal cord.

Such medications can also be injected into a specific facet joint under the guidance of fluoroscopy. Botox injections, which Liu performs, can temporarily stop the nerve signals that lead to painful muscle contractions.

Selective nerve root blocks (injecting steroids and anesthetics into a specific nerve where it exits the space between the vertebrae) can confirm the source of the pain as well as relieve it.

These blocks are performed by Liu as well as Duke interventional radiologists, who offer these outpatient spinal injections guided by CT scan. Imaging helps the injectionist place the needle precisely at the nerve or disc that shows degenerative changes.

Rahn says that these injections can aid in diagnosis if a patient may have problems in more than one area of the spine and the doctor wants to know which is causing the most pain.

"If an injectionist does a nerve-root block on one level and you don't get any relief, but on a different level you do, then that can provide some clues," Rahn says. "We're very lucky that we have several providers here who can perform this service."

A Destination for Tough-To-Treat Pain

For pain that doesn't respond to such treatments, patients can get comprehensive evaluation at Duke's Pain Clinic, which offers pain management specialists, neurologists, neurosurgeons, interventional anesthesiologists, psychiatrists, and psychologists under one roof.

Many of the patients seen at the clinic have "failed back surgery syndrome" -- persistent post-operative pain.

One of the causes is scar tissue that puts pressure on a nerve, says Parris, the clinic's director.

"Surgeons can't control the accumulation of scar tissue," Parris says. "Different people produce different amounts of scarring."

For such patients, the clinic offers specialized therapies, including a new procedure offered at only a handful of places -- percutaneous neuroplasty.

For patients with spinal stenosis and failed back surgery, this treatment involves injecting a 10 percent saline solution (hypertonic saline) that may dissolve scar tissue. Guided by fluoroscopy, the doctor injects the precise disc affected.

At the October 2007 meeting of the American Society of Anesthesiologists, Parris and colleagues presented results of a small study demonstrating the efficacy of this procedure [abstract available at www.asaabstracts.com].

Other treatments circumvent the nerve signals that cause pain.

For instance, ziconotide (Prialt) is administered directly into the spinal cord fluid through an implanted or external pump. Ziconotide is for patients who haven't responded to narcotics or for whom narcotics are contraindicated because of allergies or addictions, Parris says.

The clinic also offers nerve ablation for patients who have failed more conservative therapies, and for patients with nerve injuries, the clinic can implant a spinal cord stimulator that blocks pain "messages" using a small electrical stimulation that the brain doesn't perceive as painful.

"This is not for everybody," Parris cautions. "In the wrong patient it could be harmful."

In addition, psychiatrists and psychotherapists at the clinic treat the depression that can accompany chronic pain, and biofeedback is also offered.

"It's a very good adjunct therapy, to learn how to relax, how to cope with the pain," says Billy Huh, MD, PhD, associate professor of anesthesiology.

"The mind is a very important part of pain management."

Surgery: The Path Less Traveled

Patients shouldn't enter surgery territory until they've tried conservative therapy for at least three months, and more likely six, without success.

Even then, doctors reserve surgery for those with classic symptoms of particular conditions that also show up on imaging studies.

"Surgery can be very effective for back pain, but it needs to be directed to the diagnoses that clearly improve with surgery" -- such as spinal stenosis, adult scoliosis (curvature of the spine that's not congenital), and degeneration of a single disc, says neurosurgeon Rob Isaacs, MD, assistant professor of surgery and director of spine surgery.

To address the full range of patient needs, Duke's multidisciplinary spine surgery team includes both neurosurgeons, such as Isaacs, Michael Haglund, MD, PhD, and Carlos Bagley, MD, as well as orthopaedic surgeons such as Minchew, Richardson, and Christopher R. Brown, MD.

Brown, an assistant professor of orthopaedic surgery, says that the pool of surgical candidates has narrowed in the last 10 to 15 years.

"I don't do surgery for back pain. I do surgery for spinal instability," he says.

That's a broad term for any condition that causes the vertebrae and discs to interact abnormally, for instance when one vertebrae slips upon another (called spondylolisthesis). Patients with instability will often have pain that radiates into the legs and impedes walking.

A patient with a badly degenerated disc may be a candidate for fusion surgery, in which doctors remove the disc, then graft on bone and sometimes insert screws. The procedure stops the movement and reduces the pain caused by the lack of cushioning between the vertebrae.

The best candidate for a fusion is someone with degeneration in only one disc (single-level disease). Fusion does carry the risk that patients will later develop adjacent-level disease; by stopping natural movement of one vertebrae, the stress may be transferred to an adjacent one.

Artificial discs attempt to eliminate that side effect.

Disc replacements are approved by the Food and Drug Administration, and Duke does offer them, but many insurance companies won't pay for them.

Brown has performed one lumbar (lower back) disc replacement at Duke. But studies have shown that such disc replacement is only as effective as, not better than, disc fusion, he says.

Study results are better with disc replacements in the cervical spine (neck), but insurance companies often refuse payments for those as well, Brown says.

To provide more options for future patients, Richardson works with Lori Setton, PhD, professor of biomedical engineering and associate research professor of orthopaedic surgery, to engineer cells similar to the body's own that could be used to help regenerate discs.

And the researchers are trying to merge anti-inflammatory medications with proteins that will cause medications to gel around discs and stay there, reducing systemic side effects.

Richardson advises on the design of these experiments from a surgeon's perspective. But the use of such treatments is probably years away, he says.

Mapping the Best Route in the Operating Room

Isaacs and Richardson help patients now by offering minimally invasive procedures for virtually all back problems that respond to surgery, from disc degeneration to spinal stenosis.

While some traditional procedures require such drastic measures as collapsing a lung, minimally invasive surgery can be done with a few small incisions. That means fewer complications and a shorter hospital stay for patients.

"The short-term morbidity is dramatically less with minimally invasive procedures. The risk of being transfused is less, the risk of having a major medical complication is dramatically lower," Isaacs says.

Isaacs works to improve outcomes for all procedures through Duke's participation in the Degenerative Spine Study Group.

"We're linking up thousands of patients undergoing a certain procedure in the United States, and looking at the outcomes," Isaacs says.

Every time a patient has spine surgery at Duke, information about the procedure and outcomes are collected, along with that of patients at 30 centers around the country.

The data will tell surgeons whether minimally invasive procedures result in better long-term outcomes than traditional ones, and how to best perform procedures, such as whether to operate from the back or from the front.

Learning about Duke's minimally invasive procedures persuaded Carol Smith to take steps to stop hurting sooner.

She began having aching back pain around 1997. After an initial diagnosis of muscle spasms, an x-ray showed a curve in her spine.

Smith has adult scoliosis, which occurs more often in women and often worsens with age. As her curvature got worse -- in nine years it progressed from a 13-degree curve to a 33-degree curve -- the pain made it hard for her to walk and to do everyday things like shopping.

Another doctor had suggested a traditional procedure in which he'd have to cut along her spine and use a metal rod, screws, and bone grafts.

"It sounded horrendous to me," she says. "If there was no other option I probably would have gone that route, but not anytime soon."

Fortunately, she found an alternative -- and turned to Isaacs for a fusion surgery that required only three incisions in her side.

She had the procedure on a Monday and went home that Friday. Her predicted recovery time is three to six months, half the time predicted for the traditional procedure.

"Just thinking about the description of the other treatment, there's not a lot of comparison," Smith says.

"I'm so glad to have gotten it fixed. I was just really tired of hurting."

For more information about Duke's services for back pain, patients may call 888-ASK-DUKE (888-275-3853) and physicians may call 800-MED-DUKE (800-633-3853).

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Duke Transplant Center: A Matter of Life and Breath

Thu, 10 Jul 2008 08:44:36 -0400

Respiration has two parts: inspiration and expiration.

Air flows in and out of the lungs, taking sustenance into our bodies and delivering our leftovers back to the world. The flow of our breath, from our first cry to our last exhale, is our most basic function, connecting heart and brain to life as we know it.

Gordon Weeks goes with the flow. Or, at least, he does when it comes to matters of life and breath.

But he is also a survivor, which is why on April 12, at age 56, he celebrated his first rebirthday. It marked a year of living on someone else's lungs, a year since he was snatched back from the foggy line where life rubs shoulders with death.

His story is one of hundreds in the Duke Transplant Center, where the model of moving bench discoveries to bedside care takes on a new speed.

Thanks to the interchange of clinical practice and research innovation, patients for whom transplant wasn't possible a decade ago are now surviving longer and thriving after surgery.

Mr. Weeks goes south

Weeks and his wife, Shauna, live with their 10-year-old daughter on Cape Cod, Massachusetts, where Gordon used to spend much of his free time surfing.

Then one day he just stopped.

"I couldn't paddle out anymore," he says. "Didn't have the drive." He had no idea that the problem was his lungs -- as for many people with idiopathic pulmonary fibrosis, or IPF, it took years to make that diagnosis.

In November 2006, Weeks's brother Doug died from IPF. At that point Gordon himself had already been battling the disease for at least 10 years, and he and Shauna began to search for their only hope for meaningful treatment: lung transplant.

They applied to the transplant program at a hospital in nearby Boston, but waiting list was too long.

"They basically told us there wasn't anything they could do for [Gordon]," says Shauna, so the couple set out to find someone who could.

"I looked up Duke's outcomes online and they were the best. So I put Gordon and my daughter in the car and we drove to North Carolina."

That was March 19, 2007 -- one of the last days of winter. Gordon wouldn't see Cape Cod again until after midsummer.

The drive was tough, says Gordon.

"Shauna drove straight through -- 13 hours, and at one point we had to pull off of I-95 in the middle of Washington, DC, because I was so sick. Shauna had no idea what was happening to me."

What was happening was an escalating collapse of Gordon's respiratory system.
In the lungs of people with IPF, something -- no one yet knows what -- upsets the healing and repair processes in certain cells of the alveoli sacs. This thin, delicate tissue is gradually but inexorably scarred, and ultimately the alveoli can no longer broker the blood's precious exchange of oxygen for carbon dioxide.

The prognosis for IPF is always poor, but the process can take decades to reach a life-threatening stage; Gordon calls the disease a "sneaky one, a faker."

There's no pain, and no sensation that you aren't getting enough air (at least early on). Mostly, he says, it's a disease of frustration.

"You just sit around a lot more than you used to." And then, sometimes all at once, "the disease can just slam you."

In the lobby of the Millennium Hotel in Durham, where Shauna was checking in the road-weary family, that's what happened.

"I started shaking all over," says Gordon.

EMTs were called and he was admitted to Duke University Hospital, where the transplant team took over.

"I basically appeared to them out of nowhere, essentially waltzed in off the street totally unannounced," says Gordon, "but they immediately took me in and started rooting for me."

Gordon was stabilized and then spent the next week undergoing the rigorous physical and psychological evaluation for transplant.

"I remember that the whole transplant team gathered around Gordon's bed," says Shauna. "I was so sure they were coming to tell us that they couldn't do the transplant.

"And then one of the team members said, 'Mr. Weeks, you're having a very bad air day, and you needed a lung transplant yesterday. We're here to help."

Gordon then began the pre-transplant rehabilitation program at Duke's Center for Living, which helps lung transplant patients get strong before their surgeries. All transplant patients are required to do four hours of cardiovascular rehab training, every day, for 24 days prior to their operation and for 24 days afterward.

"The whole Duke team is really adamant about exercise," Gordon says.

So, as the Weeks family awaited a pair of lungs, Gordon hit the gym.

At this point, no one knew just how close he was to dying.

Waiting for the call

"We were desperados in desperate times," Gordon says of his peers awaiting lung transplant.

Particularly, he says, at the Center for Living gym, where patients walk the treadmills, ride bikes, and lift weights, always with oxygen tanks in tow.

Those awaiting transplant range from young people with cystic fibrosis -- some of whom get multi-organ transplants -- to older people with emphysema and IPF patients like Gordon.

One woman Gordon got to know had a disease that actually turned her blue. She, Gordon says, waited several weeks for her transplant -- but that's an exception to the rule.

The waiting time of lung transplant patients at Duke is unusually short -- about two weeks, in most cases.

Robert D. Davis, MD, a cardiothoracic transplant surgeon and director of the Duke Transplant Center, says the short wait is made possible by the program's ability to procure about three times more lungs from donors than most other American programs.

"A lot of that has to do with the fact that we'll consider organs that other people won't," says Davis.

That doesn't mean that they take lungs that are sub-par, he says, but that they have the resources and manpower to travel to a hospital that has a potential donor match.

Davis says that when surgeons physically go to look at potential donor organs, "you can do things to optimize the lung function before procurement. It allows us to use a lot of organs that are viable, but might not sound so over the phone."

The national standards for allocating donor lungs were changed in May 2005.
Originally the allocation was done on a sort of first-come, first-served basis, but the revisions now give highest preference to patients whose odds of survival after transplant are good and whose survival without transplant is dire.

And there wasn't much about the Weeks case that wouldn't turn out to be dire. On the fourth morning of his rehab training, Shauna called the paramedics.

As Gordon puts it, "I was tanking."

"Mr. Weeks's illness had progressed to the point that the trip and the transplant evaluation were too much stress on him," says Duke pulmonologist Scott Palmer, MD, who is medical director of the lung and heart-lung transplant teams.

"By the time he got to us, his survival could have been measured in weeks."

Back in the hospital, Gordon was put on a ventilator to help him breathe. But the ventilator quickly proved inadequate; it was giving Gordon oxygen, but his lungs couldn't do anything with it.

"They called my wife and more or less said, 'Please come quickly, your husband is about to die,'" says Gordon.

But he wasn't afraid at any point in those last moments of consciousness. "I really went through the whole thing like a piece of wood floating in a river," he says.

"I just thought, well, I'm putting myself in their hands and God's, and it's going to be fine, one way or another."

Uncharted waters

"The first time I met the transplant surgeon, they had just coded my husband," says Shauna.

Davis told her that they were entering uncharted waters: most patients who are at this stage of IPF are no longer good transplant candidates.

But, Davis said, if lungs became available in the next five days, they would perform the surgery.

Meanwhile, Gordon would have to be put on ECMO -- extracorporeal membrane oxygenation, which is essentially a last-resort therapy for patients whose lungs are simply unable to function.

It's a rather gruesome-looking scenario: large catheters are run in through the neck and out through the groin, so that they can capture blood from the large veins and run it through the machine's belly.

Much like a heart bypass or dialysis machine, ECMO is the mechanical means to do what the body's own system cannot -- in this case, to filter the blood's carbon dioxide and replace it with oxygen.

ECMO can be a lifesaving tool for some patients, particularly premature babies with still-forming lungs, because it provides a bridge to keep the body going if the lungs simply need to go off-duty for a while. But Gordon's lungs weren't going to get any better -- his lungs were gone.

Gordon meets his match

"I'm still not sure what it was about me that made them decide to do the transplant -- I was so sick," Gordon says.

Davis explains that such a choice is made by gestalt: The weeklong evaluation gives the team -- which includes surgeons like Davis, pulmonologists like Palmer, nurses, transplant coordinators, and social workers -- a chance to assess a variety of physical, psychological, and social support factors that help them determine whether the patient has a reasonable chance for a successful recovery after transplantation.
Lung transplant surgery is a huge commitment, on the part of the patient, the patient's family, the hospital, and the organ donation service.

Ideally, Davis says, the final decision to go through with a transplant isn't made in an emergency situation, but in those cases "it often has a lot to do with how healthy the patient was before the crisis," he says.

"Gordon was in reasonably good physical condition before he took the sudden downhill turn."

The fact that Gordon suffers from IPF also made transplantation a clearer choice, according to Palmer.

"We knew we were giving him a survival benefit, because he had no survival left with his lungs. There are other diseases where we really debate about how much of a benefit we're offering."

For example, the number of emphysema patients receiving transplants has gone down in the last five years, for two reasons: first, emphysema patients are not as sick as patients with illnesses such as IPF, and second, it's not as clear whether their survival and quality of life will be better if they are transplanted sooner rather than later.

"We want to maximize everyone's life expectancy," says Palmer, "so we want to time the transplant so that they really are at the end of the road with the lungs they have, and that they can have a good recovery and good quality of life after transplant.

"There's no crystal ball to it, and sometimes it's hard to know what's best."

After all, the surgery is no small affair.

"To make the recovery easier, they make the incision from armpit to armpit; they open you up like a clam," says Gordon.

His own turn on the table came after four days on ECMO -- Shauna says it was just as he was starting to look "really bad," if it was possible to look worse than he already did.

Gordon's surgery was as arduous as the family's drive from Cape Cod three weeks before: it took 14 hours and, when Gordon began to hemorrhage at one point, more than 100 units of blood.

Kidney envy

Even from his most precarious moments in surgery, Gordon had great odds. Fifty percent of Duke lung transplant patients survive at least eight years following their surgery (the national figure is four years).

Davis attributes these outcomes to a number of factors: only double-lung transplants are performed (their outcomes are better than single-lung transplants); the team does a large volume of transplants (also associated with better outcomes); and they employ a clinical protocol to help prevent the new lungs from injury due to gastric reflux.

"Some of it is also the sum of all sorts of little processes," Davis says. "The expertise and dedication of the physicians, the coordinators, the team aspect of delivering care -- we're still doing the same protocol as institution X, but we're doing it better."

But as good as Duke's lung stats are, they still aren't as good as the average successes for heart, or kidney, or liver transplants, which function successfully for up to 14 years.

Palmer notes that, worldwide, lung transplants have the lowest numbers in terms of both incidence and successful outcomes.

"But to me, that means we have the most opportunity to make an impact," he says.
"We don't want to just do more lung transplants. We want to extend the longevity and quality of our transplants."

Most lung transplant patients eventually succumb to either infections or, most commonly, chronic transplant rejection: at some point, the immune system registers that the transplanted organ is foreign material.

Thinking it's doing its duty, it sends its cellular troops to attack the infidel. Immunosuppressive drugs are used to keep this response in check, but often the body's impulse to defend itself simply takes over.

"Kidneys now have about a 10 percent acute rejection rate at six months," says Palmer, "and we still have about 50 percent acute rejection at six months."
He explains that, for lungs, the current immunosuppressive medications aren't making the grade.

"Lung transplant has basically just been borrowing all the drugs from kidney transplant, because they're all we've got. But the reality is that they don't work as well for us."

Some other mechanisms are at play in lung transplant failure -- the question that preoccupies Palmer and Davis, who each lead research teams on lung rejection, is what these mechanisms are, and how they can be dampened down to keep patients like Gordon alive.

Innate impulses

Why transplanted lungs succumb to rejection faster than other solid organs is a tricky question.

At first glance, the immune response makes no sense: of all the solid organs, our lungs are designed to deal with foreign matter.

The average person inhales about 26,000 times a day, taking in about 14,000 liters (or 150 bathtubs' worth) of air. With every inhale, we breathe in foreign materials along with our essential oxygen -- gasses and chemicals, particulates and microbes of varying sizes. And our lungs are set up to capture all this foreign material while not overreacting to it.

"The normal process is that the immune system operates to just get rid of the junk -- swallow it up in macrophages and dispose of it," Davis says.

But in a transplanted lung, because the lung itself is not 'self,' these injuries that otherwise would not have any consequence trigger an immune reaction that could degrade the lung and ultimately cause failure.

"We get what seems on the surface to be classic immunologic rejection," says Davis.

When a transplanted heart, lung, or liver is rejected, it's taken down by the body's adaptive immune system: T cells and antibodies are sent out specifically to attack any cell that registers as this foreign type.

Palmer says that in the lungs a different sort of immune rejection may be at work.
"Because the lungs are constantly exposed to the environment, they have an intrinsic set of defense mechanisms that are there to deal with all the stuff you're breathing in."

This is known as innate immunity, and it's a more generic immune response, involving inflammation, a cascade of antagonizing proteins, and a flood of white blood cells.

"My idea is that this facet of the immune system plays a central role in orchestrating and regulating rejection in lung transplant."

It's a new idea, and one that will take time to prove. Palmer is currently looking at how genetic variations correlate to innate immune responses and rates of rejection after transplant.

"The hope would be that someday we could better gauge your risk for rejection after transplant based on some of these genetic variations in your innate immune system," perhaps clearing up the crystal ball to help select which patients might benefit most from transplantation.

Gut reactions

Any toxins, pollution, and infections that a lung transplant patient breathes in have the potential to trigger lung injury and rejection episodes.

But the battle most often begins with the gut.

Lung transplant patients have a high incidence of gastric reflux disease, which puts them at high risk for aspiration events, in which reflux travels into the lungs, sounding the immune system's alarms.

Davis says the high rate of reflux is in large part because the vagus nerve -- which, among many other things, regulates gastric function -- takes a beating during a lung transplant surgery.

Also, patients with end-stage lung disease have a greater amount of reflux in general.

"It may result from coughing and changes in pressure in the abdominal cavities at this stage of disease," he says.

"And the reflux may contribute to the lung disease by injuring the lungs when it's inhaled. We know it's related, and it could also be causative."

Davis's research includes investigating what happens at the point of injury.

"There's a certain amount of bacteria in the aspirate material," he says. "We're looking at whether the protein coats of these bacteria are what's triggering the immune attack on the lung."

Though conclusive explanations of the hows and whys of reflux and aspiration injury are still being fleshed out, it's inarguably a condition that lung patients want to avoid.

Duke has developed very aggressive clinical procedures to prevent aspiration injuries, says Davis, including a surgical stomach-wrapping procedure -- just as it sounds, the stomach is wrapped around the esophagus to prevent reflux from moving into the lungs.

"Our protocol seems to play a large part in our outcomes," Davis says, "and we're taking the observations we're seeing in the clinics back to the laboratory, so that we can use basic research to answer some of the still-unanswered questions."

All hail the inhale

The first breaths Weeks took with his new lungs were not his own; they were the mechanized inspirations and expirations of the ventilator, to which he remained connected for four days after his surgery.

"It was really frustrating," he says. "I'd look over and see that my oxygen level was good, but it felt like I wasn't breathing at all. As Dr. Davis puts it, it takes some time for the lungs to fly."

Weeks spent six more weeks in intensive care, beginning to recover from extreme muscle weakness and adjust to the immunosuppressive drugs that will be his lifelong companions.

"Getting up [for the first time after surgery] was probably the hardest thing ever," he says.

Not because of pain, but because of sheer weakness: before his downward spiral, Gordon was a tall, strong 250 pounds; when he left North Carolina he was down to 160.

"Every day is a different healing," he says. "There are definitely steps in the healing process, and for me it's been a long staircase."

Gordon left the hospital the weekend of July 4, 2007, and went back to the rehab at the Center for Living he'd left so abruptly in April.

He says the staff there taught him -- firmly -- how to bring his body back to life after such a close courtship with death.

"I was so weak that I showed up [to rehab] in a wheelchair. And David Best said to me, 'You're not coming in on a wheelchair anymore. Get yourself a walker if you need to.'

"And so I did, and I used it for a while. Then one day he said, 'Get rid of that walker!' So I kicked it to the side as I walked in the door, and that's where it stayed."

Scott Palmer has two pictures of Gordon Weeks: one taken when he was on ECMO -- about as far from the New England surf as he could be -- and one taken recently at his home in Cape Cod, where he's built back up to 190 pounds and is able to spend most days on the job, which for him is splitting wood -- about as far from ECMO as one could imagine.

Palmer says that, though Gordon's story is particularly hair-raising at times, it's still typical of the everyday miracles he sees in the Duke Transplant Center.

"When I started doing lung transplant," he says, "I told my patients that they have a 50 percent chance of living five years.

"Now I tell them eight years, and it's pretty amazing to see that change in 10 years."

"It's not for the faint of heart," says Gordon of this process of surgical rebirth. "But the drive to live is so strong -- you don't want to let go. And as much as it hurts, and as weak as you are, there is always tomorrow to heal, to get better. Every day you do get stronger."

And his lungs, so far, have kept him flying. "I like to talk to them -- thank them, and thank the person who gave them, even though I don't know who that person is.
"I keep going back to how incredible that part of it is. One forfeits his or her life, but gives life to another, and there are people here who can make it happen."

For more information about organ transplant services at Duke, call the transplant office at 919-684-5926.

Gordon and Shauna Weeks found Duke's transplant outcomes information (and that of other hospitals) on the Web site for UNOS, the United Network for Organ Sharing.
Read more about that organization at unos.org

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Multi-Vessel Heart Disease

Thu, 10 Jul 2008 13:54:42 -0400

Hundreds of thousands of Americans are diagnosed each year with coronary artery disease (CAD), a life-threatening narrowing or blockage in any of the four arteries that feed the heart.

The leading cause of death among both women and men, CAD claims some 500,000 lives in the United States each year -- and comprises more than 70 percent of all heart disease mortality.

While some patients experience no symptoms until they suffer a heart attack, coronary disease often causes symptoms such as chest pain (angina), shortness of breath, fatigue, lightheadedness, and nausea, with patients becoming increasingly weak and debilitated as the heart is starved of oxygen.

Untreated, CAD usually means fewer years of life -- and less quality to those years. In general, the more arteries involved, the sicker the patient. People with multi-vessel disease are often scared, confused, and overwhelmed.

Nearly all say that they just want to get it "fixed."

That's where things can get tricky.

So tricky, in fact, that the first annual Thomas Ryan, MD, Duke Heart Center Lecture, held at Duke in late 2007, was dedicated to debating this important issue.

Entitled "Multi-Vessel Coronary Disease: PCI, Surgery, or Maybe Both Are Wrong?," the event began with the presentation of a case study by moderator Mark F. Newman, MD, chair of anesthesiology.

Newman reported the particulars of patient "Mr. G," as well as his angiogram results, which revealed coronary disease in three arteries.

The case was then discussed by Peter K. Smith, MD, chief of the Division of Cardiovascular and Thoracic Surgery, and Robert M. Califf, MD, and E. Magnus Ohman, MD, both of the Division of Cardiology.

Each spoke primarily in favor of a different intervention for patients who, like Mr. G, suffer from multi-vessel disease, their positions reflecting the larger ongoing debate within the medical community.

Those interventions fall under three main categories:

Percutaneous coronary intervention (PCI)
"Surgery," which typically refers to the coronary artery bypass graft (CABG or "cabbage")
Medical management

DukeMed Magazine asked Smith, Califf, and Ohman to recap their remarks on this controversial topic.

PCI: Minimally Invasive, Widely Performed

PCIs are aggressive, non-surgical procedures used to clear narrowed or blocked coronary arteries.

These minimally invasive procedures include angioplasty -- in which a balloon-tipped catheter is inserted into a blocked coronary artery and then inflated to clear the vessel of debris -- and the placement of stents, minuscule mesh-like tubes that hold arteries open.

The two procedures are commonly performed together.

The immediate risks of complications and infection associated with PCI are significantly lower than those of open surgery.

There's less post-procedure pain, recovery is quicker, and the risk of cognitive decline sometimes associated with CABG surgery is eliminated.

The preferred intervention for people in the midst of heart attacks, PCI gets blood flowing to the heart within 90 minutes, as opposed to the approximately three hours it takes with surgery.

PCI -- in particular, stenting (also known as percutaneous transluminal coronary angioplasty, or PTCA) -- has also been widely criticized.

Plagued by safety and efficacy concerns, stenting has been the topic of an ongoing debate comparing bare-metal stents (BMS) to drug-eluting stents (DES).

BMS have seen a high rate of in-stent restenosis -- plaque buildup inside a stent, which renders it useless.

DES, developed to remedy this issue, were viewed as a great advance. But when studies(1) showed an increased risk of DES-related heart attacks due to in-stent thrombosis (a blood clot that develops inside the stent), many physicians went back to BMS.

Recent findings may cause them to reconsider -- again.

A study(2) of the National Heart, Lung, and Blood Institute Dynamic Registry examined the data of 1,460 DES patients and 1,763 BMS patients one year after their stent placements.

DES patients had a 15.5 percent risk of suffering a major cardiac event compared to BMS patients' 20.9 percent.

In addition, DES patients had a 43 percent less chance of needing post-stent angioplasty or bypass surgery than those with BMS. And the rate of in-stent thrombosis among DES patients was only 1 percent -- down from previous studies. A study(3) of a Massachusetts registry of 21,024 patients had similar findings two years post-stenting.

"PCI has evolved a lot and continues to evolve -- from standard balloon angioplasty to BMS to DES and now to newer forms of DES," says Ohman, who specializes in performing PCI and leads the Duke Heart Center's Program for Advanced Coronary Disease.

"It provides a new way forward for patients -- especially older patients and those with more complex disease -- by lowering the risk of recurrence and offering a tremendous reprieve from their symptoms."

PCI isn't for everyone, but for many patients, it's "a great option that's associated with fewer symptoms and a higher quality of life," Ohman says.

"When a patient is a candidate for both PCI and bypass surgery, I think it makes sense to offer the less invasive PCI as the first line of defense."

Smith, the surgeon, agrees that because PCI isn't as physically traumatic for patients as bypass surgery, it's sometimes the better option for patients who may not be well enough to survive surgery -- such as those with advanced age or prior cardiac surgery, and even some with three-vessel disease.

But, Smith believes, "It's not fair to recommend PCI for a patient and say, 'You can always have surgery later if this doesn't work.' The public gets the idea that surgery and PCI are equivalent -- which isn't true for patients with three-vessel disease, for whom surgery is life-prolonging compared to PCI," he says.

"Proponents of PCI are basically saying, 'We never said it would save anybody's life; we just wanted to improve their symptoms.' And they should acknowledge that this is the case when they discuss options with patients who have life-threatening coronary disease."

So how long must a patient feel better before "improving symptoms" can be called "saving a life"?

The randomized ARTS II trial(4), the largest follow-up study of its kind to compare surgical and PCI patients, looked at 607 patients one year out.

ARTS II showed that "the drug-eluting stent is every bit as good as bypass surgery for treating multi-vessel disease," Ohman says.

Despite the ongoing controversy, PCI continues to be the most commonly used intervention for coronary artery disease.

The American Heart Association (AHA) reports that 1,265,000 PCIs were performed in the United States in 2005 -- approximately two-thirds in men and one-third in women. (Duke cardiologists perform more than 1,300 PCIs every year.)

But while data show that stents have gotten safer, the overall use of angioplasty appears to be waning, according to a recent analysis conducted by the National Cardiovascular Data Registry.

"The rise of angioplasty procedures has leveled off and appears to be on the decline," Duke cardiologist Eric Peterson, MD, told USA Today after reviewing the data.

This could be because some believe that PCI in general is an overused strategy for treating multi-vessel disease that would be more effectively treated with CABG surgery and/or medical management.

Bypass Surgery: Tried and True

A second approach to treating CAD is the coronary artery bypass graft, an open revascularization procedure in which arteries are surgically rerouted to allow unrestricted blood flow around narrow or blocked spots.

Because it entails opening the breastbone, spreading the rib cage, and hooking patients up to a heart-lung machine, CABG is major surgery.

Patients face months of recovery time, a large external scar, and increased risk of stroke.

"The risk of stroke associated with CABG is about 10 times that associated with PCI, and strokes occur very rarely as a result of PCI," Ohman says, adding that most patients fear that CABG will result in neurological complications, as well.

Although many patients opt for PCI to avoid these risks, the AHA reports that approximately 470,000 CABG surgeries were performed in the United States in 2005 -- some 325,000 in men and 145,000 in women.

Duke Heart Center surgeons alone performed over 600 bypass surgeries annually between 2003 and 2007.

Smith says that's because the procedure is tried and true, with proven benefits and very low mortality and complication rates.

"The advantage of surgery is that it's definitive, it's durable, and evidence shows that in almost all cases, it is effective," says Smith, who specializes in performing the procedure.

"CABG completely bypasses the disease, and in many cases, it simply doesn't come back" -- particularly with artery grafting, he adds, although the disease can return with vein grafts.

A 2006 Duke analysis(5) of outcomes from more than 18,000 heart patients found that patients who received bypass surgery lived an average of 5.3 months longer than those treated by angioplasty -- and that both bypass surgery and angioplasty provided more benefit for patients than medicine alone.

Because bypass surgery has shown the greatest longevity benefit in treating three-vessel disease -- "potentially the most lethal form of heart disease," says Smith -- "it's the clear winner for many of those patients."

Ohman concurs. "CABG certainly offers the best long-term solution for some people. The more severe the disease and the more vessels are involved, the more appropriate surgery becomes."

"Select patients do require intervention beyond medical management," Califf says. "In those cases, it's the doctor's responsibility to make sure those patients understand the potential benefits and risks of the procedure they're being offered."

Medical Management: A Solid Foundation

Because it is recommended as both a singular strategy and for use in conjunction with PCI and surgery, medical management actually transcends and supplements all other multi-vessel disease interventions.

Medically managing CAD means treating the condition with non-surgical methods that include drug therapies and/or modification of lifestyle factors such as diet, exercise, smoking, and stress management.

These strategies also help prevent further deterioration of the heart muscle in patients with existing damage.

"Medical management is the bedrock of treating coronary disease," says Califf. "Regardless of anything else patients have done, medical treatment should be the standard of good medical therapy and the first option we offer our patients.

"The Duke data(6) show that patients who are on multiple effective treatments -- which can be a first-rate aspirin, beta-blocker, and statin, available for four bucks a month from Wal-Mart -- have about a twofold reduction in their risk of death compared to patients who do not adhere to their medication regimens.

"The issue is that the real benefit is in medical therapy," Califf continues.

"PCI doesn't prolong survival in most patients, so you're not losing anything there by going with medical management, and CABG obviously has a higher risk than medical treatment."

"If we cardiologists could just do our jobs in our own treatment environment and give patients simple four-dollar-a-month plans, we would save literally thousands of lives," he says.

"We need to give patients the important treatments first, and if those fail, then try the expensive and risky treatments."

Smith agrees that medical management plays an important role for surgical patients, and its use as an alternative to both PCI and CABG may be underutilized.

"Advances in medical therapy have led to more promising results than anticipated in treating patients with one- and two-vessel disease, whom the COURAGE trial(7) showed aren't being helped as much with PCI."

The key to the best outcome? Honest dialogue.

Since each multi-vessel disease intervention has its pros and cons, how does one decide which is likely to have the best outcome for a given patient?

By having a truthful and thorough doctor-patient conversation, these experts say.

"Many doctors tell their patients, 'You've got bad blockages, and we need to bypass or dilate those blockages because if we don't, you're going to have a heart attack or die,'" Califf says.

"And that's simply not validated by the randomized trials; it's not true. But it's something we frequently tell our patients because it avoids a much longer discussion about what's really going on in terms of the risks versus the benefits of these various interventions."

Risks Versus Benefits

Many people assume, for instance, that minimally invasive procedures are inherently safer -- and therefore always "better" -- than open surgeries.

Take the surgery-versus-PCI issue, for example.

"Surgery has risks like pain, infection, and recovery time that people understand up front," Smith says.

"But multi-vessel coronary disease patients should understand that PCI's ongoing cumulative risk of restenosis is less obvious, with studies showing that surgery compares more favorably to PCI the longer patients are followed."

Patients may have different perceptions of risk when considering medical management, as well.

Some may perceive this strategy as having the lowest risk because it doesn't involve any type of surgery. Others may see it as being more risky than the other options because they don't believe medication and lifestyle changes can successfully treat their heart disease.

"It's only natural for patients to think that if they have a stent placed or undergo a bypass that their disease is 'fixed' -- and doctors can easily get away with saying, 'It's lucky we found this blockage; now we can fix it,'" Califf says.

"A doctor who offers patients a potentially risky procedure must be able to show that it's likely to help them."

Another issue, Califf says, is that many patients have difficulty translating probability into risks that are meaningful to them.

For example, when comparing a treatment said to have a 10 percent risk of death with one said to have a 90 percent survival rate, people are more likely to choose the second option, even though the actual degrees of risk are equal.

Patient Factors

Patient factors that figure into the risk-versus-benefit equation commonly include:

Age and health status: A patient may be too elderly or ill to withstand surgery, for example -- or to wait for the effects of medical intervention.

Medical management alone or in conjunction with PCI may be the most appropriate choice for someone with minimal disease.

Goals, values, and concerns: A big issue is quality versus quantity of life. Some people prefer better years to more years; some, the opposite.

Patients might think about what they hope to achieve through treatment. The stamina to keep running marathons? The ability to perform daily activities and play with the grandchildren? Relief from debilitating symptoms?

Other factors can include patients' affinities for (and aversions to) particular treatments, insurance or financial concerns, and so on.

Lifestyle and compliance: Some patients follow their doctor's instructions to a tee; others don't.

Some aren't likely to quit smoking, take up regular exercise, or improve their diets; others view their condition as a call for meaningful lifestyle change. Some are very self-motivated; others might benefit from working with a health coach.

Additional Factors

Other factors also can come into play when choosing a treatment for multi-vessel disease.

"The patient made me do it" phenomenon: While patients are encouraged to educate themselves and take a proactive role in their own health, they are increasingly arriving at their initial cardiologist visits with Internet printouts in hand and a treatment in mind -- without having discussed their individual risks and benefits with their doctors, and frequently armed with data that are murky at best.

Unclear and/or biased data: Unfortunately, the large body of existing research data about treating multi-vessel CAD can lead to confusion, not clarity. The length and type of the study, as well as the number of participants, obviously influence the quality and meaning of the data.

And different uses and interpretations of the word "multi-vessel" -- which can mean two, three, or four vessels -- mean that data from studies of patients with different degrees of disease may be combined, accounted for multiple times, and/or simply unclear.

"Most 'multi-vessel' CAD studies have in fact looked only at patients with two-vessel disease -- not three- or four-vessel disease -- and the distinctions are critical in terms of both compromised patient health and the interpretation of the data," Smith says.

"People can take these results to mean what they want them to mean when making a case for or against a particular therapy."

Physician expertise and bias: A physician or hospital's experience with and/or bias toward particular treatments plays a role in which strategies are recommended to people with heart disease.

"It's one thing for doctors to advocate for the procedures they do, but it can be an entirely different thing for them to advocate for their patients," Smith says.

"We should help our patients develop a perspective beyond what happens today, present them with information honestly, and never present a procedure as an option when another one would be more appropriate."

Califf agrees. "Let's have the courage to tell our patients the truth about what we know about each of these treatment strategies, and take the time to explain all of the risks and benefits."

While the morbidity and mortality associated with coronary artery disease is devastating, both doctors and patients can thank ongoing advances in medicine for the variety of lifesaving treatment options available today.

Selecting the right one to treat a patient's multi-vessel disease means working together to make a carefully informed, patient-centered decision.

Robert M. Califf, MD, is the Donald F. Fortin, MD, Professor of Cardiology, vice chancellor for clinical research, and director of the Duke Translational Medicine Institute.

E. Magnus Ohman, MD, is a professor of medicine and director of Duke Heart Center's Program for Advanced Coronary Disease.

Peter K. Smith, MD, is a professor of surgery and chief of cardiovascular and thoracic surgery at Duke.

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Footnotes

1. 3 N Engl J Med. 2007 Mar 8;356(10):1009-19. Epub 2007 Feb 12.
2. J Am Coll Cardiol. 2007 Nov 20;50(21):2029-36.
4. Heart. 2004 September; 90(9): 995-998.
5. Ann Thorac Surg. 2006 Oct;82(4):1420-8; discussion 1428-9.
6. Circulation. 2006 Jan 17;113(2):203-12. Epub 2006 Jan 9.
7. N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.

A New Normal for Cancer Survivors

Mon, 16 Nov 2009 16:02:11 -0500

One morning each week, the waiting room of the Duke Breast Cancer Survivors Clinic fills up with half a dozen women.

They make their way to the blood pressure gauge, pumping, listening, and writing down their own readings. They take their own pulses, check their weight. They even use notepad computers to answer questions about their physical, emotional, and psychological well-being.

The one thing the women don’t do in that waiting room is wait.

"It's so nice to talk to other people going through similar things," says Martha Hall, who's been cancer-free for four years and recently attended the clinic for her annual checkup.

What's more, after the women fill out their materials, instead of hanging around avoiding eye contact, they meet with nurse practitioner Kathy Trotter -- as a group. They discuss issues they face as cancer survivors: bone density, depression, weight gain, nutrition, exercise, and what they can do to take care of themselves.

The Survivors Clinic represents a new, empowering model of care -- very different from the suspense-filled annual mammogram surrounded by two hours of waiting that most survivors are familiar with.

"The focus is keeping you healthy, it's not 'You're so sick,'" Hall says. It's an affirmation of just how far these women have come -- and of how much things change after cancer treatment ends.

"You've been in the womb of care," says Bebe Guill, director of survivorship programs and services at Duke's Preston Robert Tisch Brain Tumor Center. "You've been encircled by these people who talk to you every day, every week, and all of a sudden they're gone. And you're left with this terrifying fear of, 'Who am I now? What is my life about now? And what happens if this comes back?'"

Add in that you will likely experience physical side effects (which can range from muscle wasting to infertility and even heart disease) or emotional side effects (like anxiety and depression), and a cancer survivor is faced with a new crisis: "The challenge," Guill says, "is finding a new normal."

That goes for caregivers as well as their patients.

Throughout the Duke Cancer Institute, clinicians and researchers are figuring out how care should evolve as more and more people survive cancer longer and longer, creating a new class of patients that once would have been an oxymoron: cancer survivors.

Tina Piccirilli (left), director of the Duke Center for Cancer Survivorship, pictured with Bebe Guill of the Preston Robert Tisch Brain Tumor Center at Duke.There are now 10 million cancer survivors in the United States, says Tina Piccirilli, director of the Duke Center for Cancer Survivorship, founded in 2005. Trends suggest North Carolina will have more than 60,000 new cancer cases by 2030 -- which at the current five-year survival rate of 64 percent means a good 40,000 new cancer survivors five years after diagnosis.

As the population of survivors has increased, survivorship has emerged as a distinct field of care. There are now a dozen or so cancer survivor centers nationwide, Piccirilli says, and new ones are being created each year.

Duke's program seeks to develop care that meets the needs of survivors -- and conduct the research that will identify just what those needs are.

In the 15 years she has been with Duke, Bebe Guill has seen the shifting tides of survivorship firsthand.

Cancer, she says, "is not a linear process, the way we used to think about it: you get the diagnosis, you get a little treatment, either you're cured or you die. Cancer is becoming a chronic disease."

That's why, Piccirilli says, the Duke Cancer Institute has adopted the National Coalition for Cancer Survivorship's definition of cancer survivor: "You're a survivor from the day you're diagnosed -- which is a hugely positive message."

Care is changing to reflect that attitude. At the brain tumor center, clinicians and patients begin creating a survivorship plan from the start of treatment. Caregivers discuss the long-term effects of brain cancer and various treatment options as clinical decisions are made, and offer both medical and psychosocial resources throughout treatment to help patients manage or adapt to those outcomes.

With brain tumors, cognitive deficits are a frequent result of the tumor or its treatment -- the ability to solve problems, to pay attention, to multitask.

"Short-term memory loss," Guill says, "is common in our patients and can make day-to-day life very difficult and frustrating."

So patients need not just medical care but the kind of support services that will help them adjust to changes in their relationships, their earning status, their independence.

This fall, the brain tumor center is launching a new survivorship clinic that will pull together a range of resources to help survivors cope with their changed status.

In addition to offering clinical surveillance and preventive care, and recommending interventions for effects such as neurocognitive deficits, sexual dysfunction, or vision and hearing problems, the clinic will offer guidance for practical concerns -- such as returning to work or coping with an inability to drive -- and connect survivors with wellness resources to aid their recovery.

A key part of that is support from others who are going through similar experiences, says Guill -- so the clinic will incorporate a patient and family support group, as well as a "lunch and learn" group where experts will discuss vital topics such as managing fatigue and depression or coping with behavioral changes.

Other specialized clinics for survivors are also popping up around Duke -- including programs in the works for prostate and other cancer types, in addition to the Breast Cancer Survivors Clinic, launched in February -- to better meet survivors' broad range of needs.

In the action-packed breast cancer clinic, for example, patients benefit from the self-assessment of weight, pulse, and blood pressure, plus facilitated group discussion and education.

Then they go on to individual appointments, whether for mammograms or bloodwork, nutrition consults or physical therapy, or one-on-one time with nurse practitioner Kathy Trotter, where they complete a long-term care plan to share with their primary care physician.

When necessary, they schedule appointments with the oncologist as well. Each woman ends up spending the same few hours she would have devoted to her checkup, but she’s seen multiple practitioners and wasted no time.

"This may be the first survivorship clinic in the United States to combine both group and individual support, assessment, and education within a single visit," says Trotter, adding that she hopes it will serve as a national model. "It's designed to empower survivors -- and they love it."

Plus, adds clinic medical director Kelly Marcom, MD, the new clinic benefits women through not just how they spend this time but where they don’t spend it: in the oncologist’s waiting room.

"Not to sound callous, but if you've been treated for early-stage breast cancer and are hopefully cured, you don't necessarily want to be in a clinic with people who have had a recurrence," Marcom says.

Hall agrees: "I just said to a friend, every time I go in [to the oncologist] I cry -- it just brings it all back like it was happening today."

"It's a symbolic moving on in their lives," Marcom says. "We can overmedicalize their lives -- that's not a good thing.”

From Patient to Person

Amy P. Abernethy, MD That is a growing consensus, says Amy Abernethy, MD. Abernethy directs the Duke Cancer Care Research Program, which "tries to move the philosophy of whole-person care into real clinical space" at every stage of survivors' care.

"We are systematically developing new models of care to do a better job of taking care of the individual patient," Abernethy says.

She looks at what she calls the "misery line," a representation of the cumulative effects of cancer and treatment: pain, fatigue, difficulty getting around, nausea. "If you plot this across time, this is a volume of misery, and my job is to decrease the misery line."

The first job is to measure that misery, via clinical trials that focus on quality of life. Abernethy cites as example a trial now under way in the sarcoma clinic, where patients answer a computerized series of questions regarding their physical, psychological, and emotional states:

Are they in pain? Depressed? Functioning poorly or well?

Those data can be tracked over time as they progress through treatment -- and then compared with therapeutic actions taken to see what seems to be working.

"We're just at the starting point of identifying trends in the data, looking at what happens to things like pain or depression over the course of treatment," Abernethy says.

"Then we bundle that information and report it back to the clinicians so they understand what kind of things people are dealing with. And as soon as we've got a sense of that, we can start bringing in new services, new products to help them cope."

This data-gathering helps make a whole of both patients and their care.

"It doesn't really help if I just take care of pain, or of nausea and vomiting. Those are isolated events in a whole person," Abernethy says.

"How do we wrap it all together? That's my ultimate goal."

Preserving Fertility

Susannah D. Copland, MD, MSAs survivors pass from active treatment to one, three, five or more years of remission, new concerns arise -- many that might not even be on the patient's radar screen at the time of diagnosis.

Consider oncofertility, the relatively new arena addressing the effects of cancer treatment on fertility.

"When people weren't surviving their cancer, nobody cared whether they would have been fertile," says Susannah Copland, MD, of the Duke Fertility Center. Today, it's a vital question for young people facing a cancer they can legitimately hope to survive.

So Duke oncologists have added a question to their intake survey to trigger the conversation, and if a patient expresses interest in future fertility, Copland is called in to discuss their options before, during, and after potentially damaging chemotherapy.

Male adults face relatively few problems, Copland says: "Sperm freezing is one of the most established methods of fertility preservation." Even if radiation or chemotherapy leaves a man sterile, his own sperm can be collected beforehand for use in in vitro fertilization (IVF).

For women, the obstacles are greater.

"The first question we ask is, do we have time?" Copland says. If a woman has a little time and a partner, her eggs can be gathered and fertilized and the embryos frozen. The largest group of such patients are women with breast cancer who have had surgery and are waiting to heal before they start chemotherapy.

That healing time can be used for IVF, though since IVF raises estrogen to many times its usual levels and some breast cancers are hormonally responsive, Copland works closely with patients' oncologists.

"We can take the medication to a level where the estrogen is only twice the woman's normal level," which oncologists find less worrying.

The embryos created through IVF can then be frozen -- a well-established practice -- until the woman makes her decisions about pregnancy. Some forms of chemotherapy leave women menopausal afterward, so women without partners or donors may consider freezing eggs.

Duke is initiating a clinical trial to offer the investigational procedure, which is newer than embryo freezing and has lower pregnancy rates.

"All those freezing options require time [for stimulating and gathering eggs] and the comfort of her oncologist with increased hormone levels," Copland says. "What does not is freezing ovary tissue. If a woman is at exceedingly high risk of losing ovarian function, we can do a laparoscopic surgery to remove one ovary and freeze it."

Duke is liaised with the National Physicians Cooperative to Preserve Fertility for Female Cancer Patients, a multi-center study of ovarian tissue freezing, which is a more invasive and experimental procedure.

"You are investing in hope," Copland says.

Should a woman who has not chosen any of the freezing procedures turn out menopausal after treatment, she's still not out of options: she can try IVF using an egg donor. "I think for many women it's a relief to hear there are options afterward," says Copland.

Copland and other Duke researchers are also studying the root causes of ovarian dysfunction after chemotherapy. Copland is collaborating on a grant to fund a study to follow patients through their treatment, measuring ovarian function markers to learn more about what's happening to their ovaries.

"That will give us better information than just 'this woman took chemo and didn’t get her period back, and this is how old she was.'"

Helping Hearts

Pamela S. Douglas, MDAcross the medical center, Pamela Douglas, MD, Ursula Geller Professor of Research in Cardiovascular Diseases, is studying heart disease in cancer survivors.

Anthracyclines, used in chemotherapy, cause heart weakening in many patients: "They can damage the heart muscle," Douglas says, "and can also damage blood vessels, leading to hypotension or kidney failure."

Newer targeted cancer therapies such as bevacizumab (Avastin) and trastuzumab (Herceptin) have also been linked to an increased risk of high blood pressure and heart disease.

Studies have shown that up to 4 percent of breast cancer patients taking trastuzumab have symptomatic heart failure and 10 percent have reversible heart problems.

Douglas is leading clinical studies to better understand the connection between cancer treatment and heart disease. "We have fairly crude measures" of the cardiac effects of chemotherapy, she says. "Heart failure is not the way anyone would like to diagnose a side effect."

So she's testing novel uses of echocardiography -- a noninvasive test that doesn't use radiation -- to see whether it does well at predicting which cancer patients might go on to heart failure.

More general trials include detailed cardiac monitoring of current cancer survivors to build up a database that could be mined for more evidence about which cancer patients develop heart disease and why.

Part of the reported increase in heart disease among breast cancer survivors may be simply a matter of numbers, Douglas believes: "Because the cancer cure rate is so high, people who survive are going to die of the kind of diseases that women who don't have cancer get."

The Exercise Connection

Lee Jones, PhD, co-director of Duke’s Tug McGraw Research Center, is studying a simple approach that could stave off the muscle atrophy that often accompanies cancer treatment—and possibly even cancer itself: exercise.Lee Jones, PhD, co-director of Duke's Tug McGraw Research Center, is studying an approach that could be used to stave off not only heart problems, but the muscle atrophy that often accompanies cancer treatment -- and possibly even cancer itself.

The miracle treatment? Good old-fashioned exercise.

Many cancer patients take catabolic steroids, which cause muscles to waste away, with major effects on their quality of life -- though "believe it or not we haven't got a good handle on how to quantify that," Jones says.

So, in a study funded by the National Cancer Institute, he is conducting strength testing and muscle measurement to study those effects over time among individuals with primary brain tumors.

"The next step will be to do biopsies and genetic screening" to isolate genetic markers for patients most likely to suffer severe wasting.

The data will also show when the wasting becomes most severe: "This will inform the timing and type of intervention that may have the most benefit," says Jones. "Say, we know this patient's going to experience muscle dysfunction, then we can be proactive and intervene before dysfunction occurs."

Regarding the cardiac disease so many survivors get, Jones is collaborating with Douglas to investigate whether exercise can prevent heart damage associated with certain types of chemotherapy and reduce the risk of cardiovascular disease in long-term survivors of breast and prostate cancer.

In a study funded by the Lance Armstrong Foundation, Jones is also examining the effects of exercise in patients undergoing active treatment for early-stage lung cancer, and says, "They're doing better, and they're feeling better."

The next study will investigate which type of exercise is most beneficial for these patients and whether exercise can impact long-term quality of life as well as overall survival.

But Jones is most excited about whether exercise can itself help shrink tumors: "Put a tumor in a mouse, exercise the mouse, and the biology of the tumor will change."

He's now working with breast cancer patients in a novel study investigating whether exercise can improve chemotherapy's effectiveness in killing breast cancer cells. "This will be the very first study to look at the effect of exercise on the tumor itself in a human," says Jones.

"If exercise can help chemotherapy work better but also protect your heart and the rest of your body from the harmful effects of the chemo at the same time, it would be just fantastic."

It would also be a great example of the direction in which cancer care is going -- with care focused on not only beating the disease, but helping people continue to triumph in the many battles, small and large, they will face in the months and years after their diagnosis.

And as Jones and his fellow clinicians and researchers transform the landscape of care for a new generation of cancer survivors, they are helping patients close in on the goal every one of them has held since the beginning: surviving -- as well and as long as possible.

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Sleep Chasers

Thu, 21 Feb 2008 16:23:39 -0500

Move over, Manhattan. It used to be that, outside of the world's most urban areas, the night belonged only to stoics like doctors on call, cops, and truck drivers.

But now that so much of modern culture and commerce aspires to 24/5/365, the sleepless most anywhere in America can pass the night from the 24-hour Wal-Mart to the 24-hour Kinko's to their 300-channel cable TV and the World Wide Web, where it's always daylight somewhere.

Want to wake up in a city that never sleeps? You probably already do.

Perhaps that’s why sleep medicine, once something of a backwater specialty, is now experiencing an unprecedented heyday. In a clear sign that the specialty has arrived, the American Board of Medical Specialties began offering physicians board certification in sleep medicine in 2007.

“I think sleep is in the public consciousness,” says psychiatrist Andrew Krystal, MD, who directs the sleep research program at Duke. “It’s hard for me to believe that people are sleeping worse now than they were a few decades ago, but it seems that people are talking about it more. Ambien is a household word now, like Prozac.”

In the Triangle, while growing ranks of insomniacs fill clinicians’ offices, sleep labs are running ever-more recordings of the squiggles and lines that describe the landscape of nightly repose -- or the fitful lack thereof. The Duke Sleep Disorders Center -- one of the country’s oldest, and one of the few in the nation that offer faculty expertise in neurology, pulmonology, psychology, and psychiatry -- moved its clinical sleep laboratory to Durham’s Millennium Hotel in November 2005.

The setting not only provides patients with a less hospitalized and more amenitized way to undergo a sleep study, but also upped the number of beds, in order to accommodate increasing referrals from physicians and patients themselves. It seems that the long-sung refrain of sleep medicine experts is finally catching on: How can we ignore any chronic disruption in something that all of us are wired to spend a third of our lives doing?

A Strategy for the Bed Battlefield

By far, the number-one disorder of sleep is its painful absence. We live in a sleep-deprived culture, but beyond our self-imposed sleep debt, on any given night at least a fifth of our populace is watching the alarm clock in waking misery. There is good news for those with chronic insomnia: There’s a well-proven, drug-free treatment that works well for the majority of patients. The bad news? Only about 100 psychologists in the country are trained and board-certified to provide it.

One of them -- Duke sleep psychologist Jack Edinger, PhD -- pulls a dust-covered briefcase from the corner of his office in the Durham VA Medical Center, opening it to display a tool from the early days of this now-proven prescription for insomnia, cognitive behavioral therapy (CBT).

“It’s a timer with an alarm on it, and a tape recorder,” Edinger says of the circa-1970s machine. “It was set up to beep, very softly, several times throughout the night; when it beeped it would turn on the tape recorder, and the patient had 10 seconds to say ‘I’m awake.’ Then in the morning you could reconstruct the night of sleep or wakefulness.” The device was among the tools used by a small group of researchers, including Edinger, to develop and prove the effectiveness of CBT for insomnia.

“It’s not rocket science,” says Edinger of his craft, but it is one that was painstakingly designed to target and disengage the behaviors and anxieties that can perpetuate sleeplessness.

Most people with chronic insomnia are stuck in a self-perpetuating loop: Their anxiety about not getting enough sleep keeps them hyper-aroused at night, both mentally and physically. Meanwhile, they’ve altered their sleeping habits -- napping, fiddling with their bedtimes, and so forth -- in an effort to coax more sleep out of their days. This sort of sleep-chasing ultimately interrupts the homeostatic drive of the body’s sleep system.

“CBT helps them right the ship again,” Edinger says. “And once they are in treatment, it’s easy for the patients to see what they need to change. Conceptually, it’s not a tough disorder to treat.” A recent study at the Durham VA Medical Center showed that people with primary insomnia who undergo cognitive behavioral therapy have excellent success rates -- 75 percent experience remission.

The caveat is that sleep research to date -- and this goes for both CBT and pharmacologic research, notes Edinger -- has focused almost exclusively on primary insomnia, meaning insomnia that occurs in the absence of other illnesses, chronic pain, and substance abuse. While people with this type of insomnia number large, they comprise only about 20 percent of all insomnia sufferers.

Edinger and other sleep psychologists at Duke are working to tweak the CBT model for patients whose insomnia is confounded by other conditions. According to current research, including three studies at Duke, the management of one hinges on the other. “If you look at people with depression, those with prominent comorbid insomnia problems are generally more difficult to manage and treat,” Edinger says.

“They also have a greater propensity toward suicide, and if you treat the depression effectively but there is residual insomnia, they’re more likely to relapse.” Conversely, treating insomnia along with depression seems to vault a patient’s progress forward. Research shows that both anxiety disorders and chronic pain are also linked with insomnia in this way: To treat any of the conditions effectively, you must treat them all.

Tangles in the Bedsheets

But there are times, says Duke neurologist Aatif Husain, MD, when a patient complaining of insomnia may actually have an entirely different sleep disorder. Husain is one of the physicians who read sleep studies at Duke’s lab at the Millennium Hotel -- one of the few in the area staffed entirely by physicians who are board-certified in sleep medicine.

In many cases, he says, the real culprit is another of the wide range of sleep-disrupting problems patients present with. Some suffer from REM behavior disorders, in which sleepers act out fearful, violent dreams at great peril to themselves and their bed partners (and which has now been linked to a subsequent onset of Parkinson’s disease).

Others have narcolepsy, which often plagues patients for 10 years before they get a proper diagnosis. That’s because most of the time its main symptoms -- fatigue and daytime sleepiness -- start in the teenage years, when fatigue and sleepiness are likely to be glossed over as the throes of adolescence or treated as symptoms of depression.

“Unless a diagnosis is made early on, it can have long-lasting consequences for these patients’ lives,” says Husain, “since they may underachieve during important academic years in high school and college.” He says that a physician can spot signs of narcolepsy in the patient history: If someone says she doesn’t sleep well at night and reports having dreams during short naps (15 to 30 minutes), she may need further evaluation.

A more common cause of sleep disruption is restless leg syndrome (RLS). Hallmarked by nighttime movement of the legs and a creepy-crawly sensation that can torment patients trying to sleep, RLS may be a disorder of dopamine levels in the brain -- much like Parkinson’s disease. In fact, Husain notes that many Parkinson’s disease patients have restless leg syndrome -- though the converse is far from true.

Husain participated in the international testing of the two medications currently approved for the treatment of restless leg syndrome, both of which are also prescribed for many Parkinson’s disease patients, although at a much higher strength. In some cases, the treatment can be as simple as an iron supplement, because there is a high incidence of low iron levels among patients with RLS. “Patients really see a significant day-to-day benefit from these treatments,” says Husain.

Breathless Nights

Even more common than RLS in patients visiting sleep labs is obstructive sleep apnea, says neurologist Rodney Radtke, MD, medical director of the Duke Sleep Disorders Center. Sleep apnea affects about one out of every 10 people, and because obesity often triggers the condition, that number could be on the rise. But Radtke emphasizes that it is not strictly a disorder of obesity: “One 300-pound man may have it while another doesn’t. And a 170-pound man may have it while a 300-pound person doesn’t.”

The toll obstructive sleep apnea takes on a sufferer of any weight can be extreme, and sleep-study footage of the condition is almost painful to watch: Over and over, the sleeping patient stops breathing; then, as the oxygen levels in his blood drop, he rouses from sleep with a jarring gasp, his heart rate leaping high as he hyperventilates. The same episode repeats and repeats, eerie quiet followed by frantic gasping.

What’s unseen on film, says Duke pulmonologist Ambrose Chiang, MD, is how this grim cycle triggers the body’s sympathetic system and increases oxidative stress, leading to endothelial cell dysfunction and systemic inflammation. This is why sleep apnea not only strains the heart but also can play a role in atherosclerosis, insulin resistance, and glucose intolerance, as well as a host of cardiovascular complications from refractory hypertension to atrial fibrillation.

“It’s such an important disease, and it affects so many organ systems,” Chiang says, noting that it’s also among the most common causes of motor vehicle accidents in which drivers fall asleep at the wheel.

The condition also brings with it a buffet of unpleasant complications that can raze the sufferer’s quality of life, from headaches and acid reflux to erectile dysfunction and nocturia (frequent nighttime urination), which is triggered by the heart’s chemical release when the body strains to breathe against a closed airway.

But because it is usually these accompanying complaints that drive patients to the practitioner, most of the time, Chiang says, the sleep apnea is not picked up. “Nocturia in particular is often misattributed to fluid intake, diuretics, or bladder or prostate problems,” he says. “Many physicians don’t know that it can be a sign of sleep apnea.”

Test of the Evil Tongues

In many cases, people who seek treatment specifically for sleep apnea are those whose bed partners have lain awake beside them, listening for their absent breathing. Chiang believes that certain patients should be screened for sleep apnea as a routine.

“Though we don’t have the studies to support this yet, it’s my opinion that every cardiac inpatient should be evaluated for sleep apnea before they are discharged,” he says. “When folks come in for an acute cardiac event and we send them home without catching their sleep apnea, they may wind up coming back.”

Likewise, he says, every hypertensive patient, every obese patient, and every insomnia patient should be screened. “ It makes good clinical sense to assess the possibility of sleep apnea in these patients -- because there are a lot of patients that we could be treating that we’re not.”

But all of these patients can’t just grab a sleep study on their way home, so Chiang hopes to improve in-office diagnostic tactics. He is working to devise an easy-to-use scoring system that could flag possible obstructive sleep apnea patients, based on the patient’s history, symptoms, craniofacial profile, and a good physical exam of the upper airway.

“If we do it right, a user-friendly scoring system could make it possible for a sleep apnea screening to be done by a physician’s staff, or nurses in a hospital,” says Chiang. “And if we can achieve this, then we’ll be able to pick up these sleep apnea patients early instead of 10 years down the line.”

Chiang shows a slide to illustrate how clearly some of the physical characteristics of sleep apnea can be identified. The slide, which he titled “The Evil Tongues,” shows six pinkish tongues displayed dragon-style, whose edges look nearly the shape of a piecrust. This kind of noticeable tongue scalloping suggests that the tongue may be too big for the mandible, and therefore likely to shut off the airway when that person sleeps.

Similar physical signs of apnea can be seen in the narrowness of a patient’s posterior pharynx or the size of his uvula or tonsils. Even facial features such as a small, receding chin or a pronounced overjet (overbite) can signal a potential obstructive apnea. “The upper airway examination has traditionally been ignored,” says Chiang. “A brief, focused upper-airway examination can be very enlightening, and it takes no more than two minutes to do.”

Patients Unmasked

While weight is a significant contributor to obstructive sleep apnea, it usually takes major weight loss to have a significant impact, Radtke says. But like insomnia, obstructive sleep apnea already has an interventional therapy that works for most people: Nasal continuous positive airway pressure (CPAP) delivered via a soft plastic mask that fits over the nose.

“If you wear it, it works,” says Radtke. “CPAP became commercially available in 1985, and we have people who have been on it for 22 years. They’ll jokingly say things like, ‘You can have my wife, but you can’t have my machine.’ It really brings a marked benefit to their lives.”

In fact, the only patients who don’t benefit from CPAP are those who don’t wear the mask. “People who have severe apnea are remarkably compliant, because of the change in their ability to stay awake and energetic during the day,” says Radtke. “They get the immediate reinforcement of feeling great. But in the mild apnea patients, who get only a modest benefit in terms of how they feel, it can be hard to put up with the aggravation of CPAP over the long haul.”

Radtke says that in these mild cases compliance is only 70 percent at best, and sometimes as low at 30 percent. “Most 40-year-olds don’t like the vision of themselves going to bed every night with a mask on.”

Husain says that the more a patient understands about the health implications of stopping breathing 50 times an hour, the better his CPAP compliance becomes. Duke’s sleep apnea/CPAP clinic was developed in part to make sure that these patients understand the importance of what the perhaps ungainly equipment is doing for them.

“Our sleep technologist works with patients to make sure they have the best-fitting mask and to solve any issues of discomfort, as well as to provide education,” Husain says. The clinic also streamlines the CPAP process for both patient and referring physician. “We arrange for the CPAP equipment to be sent to the patient’s home, and we conduct follow-up appointments and further testing when needed,” he says -- which serves the patient and saves the primary care physician potential logistical nightmares.

“When I order CPAP I have to send a prescription to a home health company, and they get the machine to the patient. But different insurance companies deal with different home health care companies, and most physicians don’t have any cause to know which works with which. It can take a lot of navigation to sort it all out.”

Educating More Bedfellows

For both apnea and insomnia, the greatest challenges aren’t in discovering treatment, but in getting the treatments to more patients. “Most patients who seek treatment for insomnia do so in a primary care setting,” says Edinger, “where the most they are likely to get is a sleep medication. Ultimately we want a model of CBT that would be practical for primary care physicians to use.”

He says there are now studies underway to look at different ways of providing CBT through nurse providers, physician assistants, or even Internet delivery systems. “In Holland they did behavioral interventions via TV,” he says. “That kind of delivery isn’t as effective as one-on-one CBT in a clinic setting, but for what it was they actually did fairly well -- and they reached thousands of people.”

Krystal is trying another tactic: Educating physicians online. “We know that physicians can improve how they manage their patients in general when they improve how they manage their patients’ sleep,” he says, but clinicians in the field currently don’t get much in the way of training to do so.

To remedy that, Krystal and two colleagues, Thomas Roth, PhD, at Detroit’s Henry Ford Hospital and Daniel Buysse, MD, at the University of Pittsburgh, formed the Sleep Medicine Education Institute, a non-profit organization that disseminates sleep medicine research findings and provides continuing medical education credit on insomnia, restless leg syndrome, and sleep apnea. The organization is funded in part by pharmaceutical companies, but the content of the information is not influenced by industry.

“It’s a means of education in which the educator is in no way compromised by commercial interests,” he says. “It allows physicians to hear from the people who are actually doing the research.”

Krystal hopes that this and similar education venues will help improve care for the hordes of patients still awaiting a consistent night’s rest. “Sleep medicine is still an area where we’re not getting any better at making the problems go away,” he says. “But we are getting better at treating it. There are effective methods out there to help people with sleep problems -- we just need more people who are trained to provide them.”

This article was first published in the Winter 2008 edition of DukeMed Magazine.

Mending Hearts

Wed, 30 Jan 2008 16:15:55 -0500

For years, Deloris Gibson had felt tired -- exhausted, really. Her doctors thought it might be allergies. Then, several years ago, when Gibson was 64, her problem worsened. “To get the dishes done, I’d do one pan and stop for an hour and rest, then do another one,” she says.

She went to a pulmonary specialist, and bought a home oxygen saturation monitor. She found that her oxygen level was at times dropping to a dangerously low 70 percent (a level greater than or equal to 90-94 percent is considered normal). She had a diagnostic catheterization, but it revealed nothing definitive. Her doctors put her on home oxygen.

In 2006, Gibson was at her sister’s house, making the Thanksgiving dressing, when she felt especially tired. “I measured my oxygen, and it was 68,” she says. She slept through Thanksgiving and two days beyond, waking only to eat. Her family wanted to hospitalize her, but she waited until she returned home to North Carolina and went back to a pulmonary specialist, then to a cardiologist, and had another diagnostic catheterization.

Gibson’s cardiologist referred her to Duke because he suspected her problem was caused by a heart defect called a patent foramen ovale (PFO). “The best way to think about it is as a trap door in the wall in the heart,” says John F. Rhodes Jr., MD, chief of clinical cardiology in Duke’s Department of Pediatrics. The opening should close sometime after birth, but in 25 to 30 percent of people it remains open.

PFOs often go unrepaired because they are considered normal. “Unfortunately, in some people, PFOs can become pathologic,” Rhodes says. “In people with hypoxemia [low levels of oxygen in the blood] we think the hole opens up, and all the blue blood goes across, causing the pink blood to be unoxygenated.”

For Gibson, Rhodes performed a catheterization to close the PFO with a Dacron-and-metal patch about the size of a quarter. Today, for the first time in years, she doesn’t depend on supplemental oxygen.

“Dr. Rhodes thought I might be on oxygen part-time, but I don’t need it,” she says. In addition, she’s been able to have knee surgery that her doctors previously considered too dangerous because of her low oxygen levels.

Gibson gets tears in her eyes when she talks about all the things she can do now -- paint her kitchen, mow her one-and-a-half-acre lawn with a riding mower, and travel. “I thank the doctors and everyone at Duke with all my heart -- including the patch over it,” she says.

From Surviving to Thriving

Fortunately, most patients with congenital heart defects don’t have to wait as long as Gibson did to reap the rewards of detection and treatment. In fact, the average age at which treatment begins has steadily dropped over the years -- and many heart abnormalities are now being identified before babies are even born.

Even better news for the estimated 40,000 infants born with heart defects each year in the United States is that improved diagnostic and repair techniques have enabled defects previously associated with high mortality to be successfully treated. From 1993 to 2003, death rates for congenital cardiovascular defects declined 31 percent, according to the American Heart Association.

“A number of heart defects that were previously considered fatal can now be treated surgically with good results,” says James Jaggers, MD, associate professor of surgery. For example, for children with single ventricle defects, in which one of the heart’s pumping chambers is underdeveloped, the survival rate 10 to 15 years ago was less than 50 percent. Today, the survival rate has risen to 85 to 90 percent.

Now that mere survival isn’t a luxury, many patients grow up with their cardiac team. Today, care focuses on helping patients of any age to thrive. At Duke, patients benefit from physicians’ experience in the most complex cases, access to a steady stream of new treatments and devices available only through clinical trials, and a team that follows a patient for as long as it takes -- often into adulthood.

Diagnosing Defects Before Birth

At Duke, physicians use ultrasound routinely to detect birth defects before babies are born. “If defects are identified early, then the baby’s delivery can be coordinated at a tertiary care center, where ICUs and neonatal and cardiology support are available,” says Jennifer Li, MD, chief of cardiovascular research in the Department of Pediatrics and an associate professor of pediatrics. “It’s also easier on the family because they learn earlier what is going on with their child and can have a consultation to find out if there are other abnormalities.”

Angelo Milazzo, MD, of Duke Children’s Cardiology of Raleigh, uses telemedicine to provide answers for expectant mothers and other patients as soon as possible. While an ultrasound or echocardiogram is performed in the Raleigh office, colleagues at Duke can see the images in real time and discuss them with Milazzo and the sonographer. Milazzo also uses telemedicine to consult live with doctors whose patients are having these tests performed at outlying community hospitals.

“Fetal ultrasounds are very complicated, technically difficult studies to do because you’re at the mercy of the position of the baby and several other factors,” Milazzo says. This is especially true when a baby is suspected to have a complex condition such as hypoplastic left heart syndrome, which represents a spectrum of different but related kinds of heart disease. “No two of these patients are alike, and it can be very difficult prenatally to determine exactly what variant the baby may have,” Milazzo says.

“We’re a full-service pediatric cardiology office, and we’re able to do the test and give the results that day. But if we have a very complicated case or a clinical question that we feel needs multiple opinions, by using telemedicine, we can do that at the time of the visit. We don’t have to say, ‘I want to discuss this with my colleagues, so I’ll bring you back in a month.’ That’s very helpful because these women are often scared to begin with because they’ve been told there may be something wrong with their baby’s heart. It’s important to give them information because they may have to make difficult decisions,” Milazzo says.

Improving Outcomes

After a defect is detected, often it is repaired through either cardiac catheterization or surgery. Duke has become a leader in both methods. Duke’s pediatric interventional catheterization lab is the busiest in North Carolina, performing 600 procedures in 2006. The pediatric surgical program has the highest volumes in the state, performing 380 surgeries in 2006.

And though Duke often handles complex cases, outcomes are superb. Out of dozens of U.S. programs involved in the Society of Thoracic Surgeons congenital heart national surgical database, Duke has one of the most complex patient populations but still has one of the lowest mortality rates, Rhodes says: “Our outcomes are as good as anywhere.” Adds Jaggers, “We specialize in taking care of the most complicated cases with excellent results that rival anyone in the country.”

One factor in that success is the ability to perform more complete repairs when patients are babies. “We do a significant number of operations on premature infants -- children as small as three-and-a-half pounds with very complex heart defects,” Jaggers says. In the past, doctors would perform smaller, temporary repairs early in life, then bring the patient back later for a bigger surgery. “Now, we tend to do a definitive repair at an earlier age,” Jaggers says.

In addition, Rhodes and Jaggers point to improved management in both the operating and recovery rooms. Developing best practices that are uniformly used has meant that patients spend less time on the breathing machine and suffer fewer side effects from surgery, such as strokes or neurological injury. “We’re interested in not only getting kids through surgery, but getting them through functional and whole,” Jaggers says.

Jon Meliones, MD, director of the pediatric ICU at Duke, has led these efforts, including a formalized procedure for transferring patients from the operating room to the ICU. First the surgeon conveys the results of the procedure, then the anesthesiologist gives a report, then the nurse repeats the information back, and the ICU physician clarifies with questions.

“Before, people would begin talking without having a plan of what they were going to say,” Meliones says. “Now, the team comes in, and we do the handoff using very scripted, stylized communication, and it happens the same way every single time.” The procedure is modeled on those used in the aviation industry to reduce crashes.

Duke has won several awards for quality for this procedure, including a scientific award from the Society for Critical Care Medicine. Articles on these procedures have been accepted for publication by the Agency for Healthcare Research and Quality.

Though repair of defects is the mainstay of treatment, care does not end there. Duke’s team of nurses, genetic counselors, doctors, and others work to treat the whole patient. “We’re looking more comprehensively at patients and thinking about the genetic causes of their heart disease, their neurodevelopmental outcomes, and how we can help maximize their developmental potential,” says Stephanie Wechsler, MD, who runs Duke’s specialized cardiovascular genetics clinic. “We are moving well beyond just survival to look at what we need to do to help these kids have as full a life as possible.”

Wechsler sees patients with congenital heart disease that accompanies other birth defects, patients with cardiomyopathies that may have a genetic basis, and patients who may have a connective tissue disorder such as Marfan syndrome. Children with congenital heart disease as well as other congenital anomalies can often benefit from finding out if they have a named genetic syndrome or chromosomal abnormality.

“That can be helpful both for planning care for the child and for letting the family and pediatrician know about other health problems that might come up in the future,” Wechsler says. In addition, Wechsler and clinic coordinator Elizabeth Heise, a certified genetic counselor, counsel families about the possibility that current or subsequent siblings may also have congenital heart disease.

Additional support comes from nurses, social workers, and even parents of other patients. Robin Wilson, a pediatric cardiology nurse at Duke, helped start a Triangle-area chapter of Mended Little Hearts, a support program for families of children with congenital heart disease. At weekly meetings held at Duke, parents receive support from each other as well as information from a guest, such as a dentist who provided heart-healthy dental care tips.

Watching Patients Grow

As treatment has improved, more and more patients with congenital heart disease are growing into adulthood. Ronald J. Kanter, MD, who specializes in treating heart rhythm problems, has followed some patients for as long as 20 years. For one patient, who first came to Duke when he was 15, Kanter has implanted three pacemakers over 15 years. “He’s now married and has a kid,” Kanter says.

For such patients, Duke offers one of the nation’s few specialty clinics providing comprehensive treatment for adult congenital heart disease. The clinic includes pediatric cardiologists such as Kanter and Rhodes, adult cardiologists, cardiovascular surgeons, and other specialists in adult congenital heart disease. Patients include a few who, like Gibson, have heart defects that were not repaired in early life.

But many have had complex defects repaired during childhood and still need ongoing care. Such patients may have recurring or new problems that can require additional surgeries or procedures to repair valves, blood vessels, or holes in the heart using new non-surgical techniques in the cardiac catheterization laboratory.

They can also develop heart rhythm problems related to scars from prior surgeries, which may also be treated with catheter-based procedures, Kanter says. And, adds cardiologist Thomas Bashore, MD, “As patients get older, they may develop heart problems that affect everyone, such as hypertension, coronary artery disease, or diabetes. These issues can further complicate their overall care.”

The clinic offers services such as genetic counseling, referrals for vocational counseling, management of issues that might arise during pregnancy, clearance to participate in sports, and comprehensive imaging techniques, such as echocardiography, cardiac CT, and cardiac MRI, to diagnose and follow these patients. Specialized services also include the newest treatments for pulmonary hypertension offered in collaboration with Duke pulmonologists.

Kanter remembers having to tell a high-school senior that he had to stop playing on his school’s basketball team. “When I met with him, I realized he had a valve disease that made it unsafe for him to continue to compete at high-level sports until we dealt with it either with a catheter-based procedure or surgery,” Kanter says.

But the teenager desperately wanted to play in his homecoming game. Kanter, despite his reservations, trekked down to the gym with a portable defibrillator to supervise while the teen played in one last game. “I felt we could take whatever minimal risk there was, and let him play, and I could be there in case he had a life-threatening heart rhythm episode,” Kanter says. Fortunately, Kanter didn’t need to use the defibrillator -- and the boy’s team won.

“I realized that like many things, in medicine there is opportunity for compromise,” Kanter says. “We have to take into account more about the patient than just their physical problem; we have to take into account their developmental level and emotional status as well.”

For more information on congenital heart disease treatment at Duke, call 919-681-2916 (general information) or 919-668-4000 (appointments and referrals). For more information about the Cardiovascular Genetics Clinic, call 919-668-2196.

This article was first published in the Winter 2008 edition of DukeMed Magazine.

The Sports Team

Mon, 11 Feb 2008 15:55:52 -0500

One youth chases another at furious speed, and when he catches his quarry grabs him by the shoulders and flings him mercilessly to the hard earth. The contact between boy and ground creates a sound so clear you can envision it in large, bright letters: THUNK! MMMMPH!

The tackled boy, being an adolescent and thus immortal, rolls, jumps up, and trots back to his team’s huddle, probably with a smile hidden inside his football helmet that says, “Hit me as hard as you want. That was 30 yards, and I’m about to get 30 more.” And so the running, hitting, falling, twisting, and blocking -- the continuous, jarring impact -- rolls on into a cold autumn night as boys from Charles E. Jordan High School in Durham and Garner High School battle for glory in the state’s high-school football playoffs.

On the sidelines pace a number people who understand the possible consequences of that impact, have helped the boys prepare for it, and are ready to respond if a boy can’t jump up from a blow.

Claude T. Moorman, MD -- who goes by his middle initial -- is the director of the Duke Sports Medicine Center and professor in the Department of Orthopaedic Surgery. Claude T. Moorman, MD, at the Jordan vs. Garner high school football gameJust before halftime, he squats before a boy on the bench who had come out of the game with a neck “stinger” several minutes earlier. He supports the boy’s wrists lightly and has the boy raise his arms to shoulder level, with his elbows at horizontal 90-degree angles. The boy doesn’t wince, but he looks tired and disappointed. Moorman gives him the OK, and the boy trots to the locker room with his teammates.

Duke Doctors, Local Athletes

Seven years ago, Moorman helped create Duke’s outreach into area high school athletic teams. Duke supplies them with orthopaedic physicians, primary care physicians, and certified athletic trainers or physical therapists, for free. Depending on the needs of the school, they might consult with coaches and school-based certified athletic trainers during the week, but at the least every Friday night in autumn they’re at football games, either at home or away, and they often attend the home games of a school’s other sports.

The program now reaches nine high schools in Durham County and one each in Orange and Wake, and Duke certified athletic trainers are at Durham middle school football games every Wednesday during the fall. Duke also supplies physicians for North Carolina Central University (NCCU) games -- and, of course, for the Blue Devils.

Usually orthopaedic residents also attend the high school games, but on this night the residents are studying for their training exam the next day. It’s a rare night off -- they must serve at 20 sporting events during their residency year, whether or not they intend to practice sports medicine as a subspecialty. Why? It’s simultaneously a service to the community, a living lab of bone-jarring impact, and way to form connections between Duke and the world beyond its walls. It’s also good preparation for the sports-related injuries the residents will likely see in their future practices.

“Hit ’em again, harder,” chant the cheerleaders to a cold crowd, as if to remind the absent doctors that they will have no shortage of patients.

The K Factor

The Duke Sports Medicine Center is built around four pillars: a sports medicine clinic, physical therapy services, a sports performance program, and research in the Michael Krzyzewski Human Performance Lab -- the K-Lab. The center, in various forms, dates back 70 years and has pushed the boundaries of orthopaedic medicine through its focus on people placing maximum stress on their musculoskeletal systems. In recent years it has greatly expanded its efforts along a continuum that ranges from research through clinical treatment to sports performance training.

Among its newer components is the 10-year-old K-Lab, directed by Robin Queen, PhD. On this particular day, participants in a K-Lab study are preparing to perform simple exercises, such as climbing a step. Small reflective markers are attached to the outsides of their knees, ankles, and hips. Eight cameras around the room capture the movement from the markers and feed computers that create digital representations of the motion of their joints.

Queen, with a doctorate in biomechanics, and researchers from Duke University Medical Center are studying several orthopaedic issues in the K-Lab. For example, three Duke specialists in hip replacement surgery utilize three different surgical approaches for reaching the hip: posterior, direct lateral, and modified anterior lateral. Each involves cutting different muscles. Outcome studies to date -- by various researchers around the country -- have been based on patient satisfaction surveys.

Improving Patient Outcomes

In this study, for which Queen serves as the principal investigator, patients who have undergone hip surgery will be examined to determine whether they have returned to walking normally. Their movement will be compared to that of a control group measured in the K-Lab. Members of the control group have been chosen to match the age, weight, gender, and other characteristics of the group that has undergone surgery.

Initially, Queen’s group is looking at patients post-surgery, but eventually the gait and movement of patients will be examined before surgery in order to compare movement before and at several milestones after the operations.

The logic is as clear as the sound of high-school athletes hitting hard ground. Patients will be compared to healthy, normal controls in order to evaluate the success of their operation in returning them to normal movement. “We’re looking at what the numbers say in addition to what the patients say,” Queen says.

Few if any similar studies have been undertaken anywhere -- likely, as Queen notes, because scientific disciplines often operate independently. “It’s a novel concept to combine biomechanics with clinical outcomes,” she says.

The same idea drives studies of hip resurfacing. Patients who have undergone either hip replacement or hip resurfacing will be compared to healthy controls, with researchers examining such indicators as hip flexion angle, range of hip flexibility, and degree of hip hike.

A similar study is evaluating ankle replacements. And as the K-Lab builds databases of movement of various aspects of the musculoskeletal system, they could be applied to future studies.

The K-Lab also plays a vital role in collecting kinematic and kinetic movement data on patients who have knee osteoarthritis in an attempt to understand how the disease alters movement patterns. “We’re looking at gait mechanics as a functional outcome following a clinical intervention of weight loss and pain management,” says Queen. This work is part of a larger NIH-funded Program Project Grant directed by Farshid Guilak, PhD, who heads Duke’s Orthopaedic Bioengineering Lab.

The knowledge generated by these studies is published in scientific journals and makes its way into the practice community through traditional routes. But the K-Lab itself also is used for immediate clinical applications, such as assessing athletes to help them improve sports performance.

Not Just for Pros

With the attention paid to athleticism at Duke Sports Medicine -- and its location in the heart of the Duke athletics complex, right next to Wallace Wade Stadium -- it is almost a surprise to walk through the clinic, with its standard-looking examining rooms, nurses’ station, and x-ray rooms. But while the Center has an obvious focus on sports-related medicine, it is not just for competitive athletes -- the team here can help anyone with musculoskeletal injury or pain who seeks to be more active than his or her medical condition currently allows.

In addition to straightforward sports-related orthopaedic services, the medical and therapeutic staff provide services specifically focused on women’s sports medicine, pediatric sports medicine, sports psychology, primary care, and rheumatoid arthritis treatment, plus an extensive on-site physical therapy program that enables seamless post-surgical care and rehabilitation.

In fact, the majority of the patients seen here aren’t professional athletes, or even necessarily serious amateurs. Most patients are self-referred, many of them simply active people who have injured themselves or people looking for help with medical problems such as osteoarthritis. On a recent day an older man with a leg brace was leaving his appointment while a young father with his elementary-school age boy were checking in.

“We’re somewhat like a ‘space program’ for orthopaedics,” says Moorman from his office overlooking the football stadium. “Athletes are always looking to break barriers that you and I don’t generally approach, and in sports medicine you get to work with problems and treatments at the edge of the scientific field. One of the results is that sports medicine has driven the development of treatments that have eventually become the gold standard for the rest of us, like minimally invasive surgical techniques and early motion, minimal stress recovery therapies.”

For example, recovery from ACL repair once took a year but now takes three to four months, thanks in many ways to practices developed for athletes. Sports medicine has also supported advances in soft-tissue healing, such as contributing to findings that the body overshoots the mark in healing and causes overinflammation, which can be mediated by anti-inflammatory agents.

Some sports medicine research even makes its way into the commercial arena. The K-Lab, for example, has provided data to help Nike improve the safety and performance of cleats and other athletic footwear. And recently Duke Sports Medicine has been involved in testing a new way to deliver electrolytes -- via an oral strip against the gums.

“When you’re active, your blood goes to your extremities, away from your GI tract, which cuts down on your body’s efficiency in absorbing electrolytes delivered through drinks -- which, of course, is the way they’ve traditionally been delivered,” explains Moorman. “People have wondered if there was a more efficient way of delivering them so that they would spread to your muscles more effectively. This strip appears to do that and decreases cramping significantly.”

The need for better delivery systems for professional athletes, who spend hours in intense activity, seems self-apparent, but the same need may exist among boys and girls who are physically active, especially those in warm climates. The number of school-age athletes has doubled over the past 10 to 15 years, says Moorman, due in large part to the influx of young women into sports.

Focus on Women

That growing population of young female athletes has resulted in the need for more sports-medicine research and treatment focused on women. Just down the hall from Moorman’s office is the office of Alison Toth, MD, who launched Duke’s Women’s Sports Medicine Program in August 2001.

The program quickly became a national hub for the growing movement to teach women and clinicians to recognize and prevent problems that plague active females -- whether they’re young Olympic hopefuls or senior citizens who want to resume a walking program after a fracture.

The Duke program was one of the first three in the country to focus specifically on women in sports and has the capability to diagnose and treat injuries that are unique to women, that manifest themselves differently in women than they do in men, or that require interventions specific to women.

Like the rest of Duke Sports Medicine, the Women’s Program isn’t just for jocks. “Our practice is for anyone who has musculoskeletal problems and wants to stay active, whether through sports, walking for exercise, or simply being able to reach overhead and comb her hair,” says Toth. “We can help people maximize their ability to stay active and remain injury-free.”

That’s the common thread among people who come to Duke Sports Medicine, it seems, whether they’re pro athletes, active seniors, or soccer-crazy kids. All seek to improve their physical capabilities in an atmosphere that helps them push their limits.

Though Dr. Toth tends to female patients' needs in the Women’s Program, she cares for just as many male athletes. In fact, she can be found on the sidelines as the head team physician for NCCU football and other NCCU teams.

Friday Night Lights

On the football field, boys are pushing their limits in order to keep their season alive, one game at a time. Ron Olson, MD, walks the sidelines of the field on that cold Friday night. Olson, the Duke primary care physician working the game this evening, has a long history in sports and sports medicine and describes himself as a semi-serious athlete. In addition to helping with the outreach program and the Duke primary care sports medicine fellowship, he looks after a few other teams and travels with the U.S. Ski Team to Europe for a week each year. As Moorman attends to a player on the bench, Olson jokes, “We let the orthopaedics people be the first responders at these games.”

Ron Olson, MD Not far away is Alanna Cooley, a Duke physical therapist and certified athletic trainer assigned to the Jordan teams. In the mornings she sees physical therapy patients at the Duke Sports Medicine Center, but afternoons are often spent at the large Durham high school, working with Jordan’s athletic trainer, Gail McMurry. At the game, both she and McMurry carry packs containing bandages, tape, scissors, gloves, and other tools to take care of small injuries.

This evening all the injuries are minor. The staff get to enjoy the game. Jordan loses, however, and so its season -- and the Duke staff’s attendance at its Friday night games -- are over for the year.

But basketball season is starting. And wrestling.

“We may even see some of these kids at the Saturday clinic tomorrow,” says Moorman as the game winds down.

Then his own team packs up and heads home for the weekend.

This article was first published in the Winter 2008 edition of DukeMed Magazine.

Meet the Dean: Nancy C. Andrews, MD, PhD

Tue, 17 Nov 2009 11:16:28 -0500

From the legendary Wilburt C. Davison to the recently promoted R. Sanders Williams, the six former deans of Duke University School of Medicine have, to a man, been exceptionally talented physician-scientists, educators, and leaders -- passionate advocates for the advancement of medicine in general and Duke medicine in particular.

Dean No. 7 is no exception.

Called "a leader who is able to take programs, organizations, and people to new heights" by her mentor David Nathan, MD, president emeritus of Dana-Farber Cancer Institute, "one of the nation's most accomplished physician-scientists," by Williams, now senior vice chancellor for academic affairs at Duke, and "the best candidate in the country for this position," by Chancellor Victor J. Dzau, MD, Nancy C. Andrews brings to her new post a record of experience and accomplishment that clearly establishes her place in the pantheon of Duke Med deans.

There is, of course, one notable difference between this dean and her predecessors: she's a woman.

As the first female dean not only of Duke’s medical school, but at any top-10 medical school in the United States, her appointment created a buzz that expanded beyond academic circles to over 200 media outlets nationwide, from the Wall Street Journal to NPR.

DukeMed Magazine recently talked with Andrews about all the attention -- and where she’ll be focusing her attention as Duke’s next dean.

After two decades at Harvard and inquiries about deanships at other institutions, why did you decide to accept the position at Duke?
"From my first visit, it was clear that Duke has a very special character -- a real spirit of innovation and entrepreneurialism. I had the feeling that this was a place where big things could happen -- where somebody could have a great idea and if it was compelling, something would come of it.

"Some of the large New England schools are so big and there's so much process around everything that it can be hard to start new initiatives. It’s like trying to change the direction of the Titanic. Here, doing new things seems to be part of the culture.”

Were you surprised at the level of media attention your appointment received?
"Kind of -- initially, I don't think any of us had really thought about my being 'the first.'

"I think it's another wake-up call for academic medicine. Women and members of underrepresented minority groups are still not on equal footing at the highest levels, even though medical school classes are more representative. I hope that it will help to have more women leaders who not only understand what the issues are for young female faculty, but are also in a position to do something about them."*

You've gotten to know Duke better since becoming dean in October. What do you see as this institution's differentiating strengths -- and its major challenges?
"Duke has a great tradition of collaboration, especially across traditional academic boundaries. Duke has remarkably strong clinical research and basic science engines, and is ready to take full advantage of where they intersect to do translational work.

"Duke also has a strong core value of being of service to society, which I think is really important. I like the fact that Duke is aggressively thinking about its global role, and reaching out to establish collaborations with academic and industry partners and other countries and governments.

It is always a challenge when there are more great ideas than there are resources to support them in terms of building space and money. So we're not in a position to do all the things that we’d like to. It's unfortunately a fact of academic life right now, especially while the NIH budget is in so much trouble."

What are your main priorities as dean?
"Education always has to be a top priority for our medical school. I want to put a lot of my attention early on into strengthening the MD/PhD program. We have very fine students and committed faculty, but we need to continue to increase the size and quality of our applicant pool, diversify the kinds of research experiences students choose, and bring more visibility to the physician-scientists who are role models for those students.

"We also want to be continuously rethinking education for all of our students, because the needs change over time.

"Another priority is to find better mechanisms and incentives for interdisciplinary work. The traditional departmental structure can pose logistical barriers for interdepartmental collaborations, and if we can fine-tune ways to manage these intersecting enterprises, that will be important not only to Duke but on a national scale.

"We're now working on the 2010 strategic plan, exploring possibilities for a new student learning center, research building, and imaging facility and contributing to Duke's initiatives in global health, genomics, translational medicine, brain sciences, and others.

"We want to make sure Duke is well-positioned not only for what’s hot today but also for the next waves in medicine."

*For more perspectives, see Dean Andrews’s editorials "The other physician-scientist problem: where have all the young girls gone?" (Nature Medicine, May 2002) and "Climbing through Medicine's Glass Ceiling" (New England Journal of Medicine, November 8, 2007).

This article was first published in the Winter 2008 edition of DukeMed Magazine.