Category Archives: Medicine

A Call For Action: Genetic Testing Before Prescriptions

January 12th, 2013

By Prachiti Dalvi

Structure of Codeine

Codeine is an opioid pain medication; but if you are a poor metabolizer of a particular enzyme (CYP2D6), you will experience no pain relief from this drug. However, if your doctor could administer something called pharmacogenetic testing, she would know to simply give you morphine (an active metabolite of codeine) instead. For now, this kind of testing isn’t available.

Mary Relling, PharmD

Mary V. Relling, PharmD, the Chair of Pharmaceutical Sciences at St. Jude’s Children Hospital spoke about the need to implement pharmacogenetic testing on Thursday, January 10. A number of  tests have recently emerged that are ready for prime time. When we know that some drugs may have adverse effects for people with  particular genetic phenotypes, it is unethical to prescribe these drugs without knowing the patient’s genetic status.

However, Relling said there are a number of barriers to integrating pharmacogenetic tests into clinical care: fragmentation of our healthcare system, a focus on sick-care rather than disease prevention, a lack of evidence for clinical utility or cost-effectiveness, complex underlying lab results, and a lack of a centralized system for recording patient information.

The best way to break through these barriers is to conduct testing preemptively, Relling said. We can simply take drop of blood when the baby is born and run genetic tests. “Genetic tests are lifetime results. It makes sense to have it in the background, just as we know a patient’s age, weight, sex, etc.,” Relling said. The barriers discussed above can be avoided to a certain extent at St. Jude’s because they have adopted a team approach to patient care and a 100% electronic system for recording patient records.

The growing affordability of genotyping makes using preemptive pharmacogenetic testing more feasible, she said. The cost of sequencing one or two genes in the past will now produce results for 225 genes. Two years ago, the Clinical Pharmacogenetics Implementation Consortium (CPIC) studied how to migrate pharmacogenetic testing from the laboratory into routine patient care. They looked for gene-drug pairs associated with potential risks of life-threatening toxicity, serious adverse effects, or lack of effectiveness. Eleven of the genes CPIC determined met the threshold for high-risk were found to have profound effects on 33 drugs.

Relling said approximately 48% of patients receiving drugs at St. Jude’s received orders for at least one of those pharmacogenetically high-risk medications.

She said the question now is how to use genetic test results rather than whether a genetic test should be ordered. In the coming years, we will have to address how to maintain the fine balance of providing the clinician with enough information to treat the patient and overwhelming the patient with genetic testing results that are difficult to interpret.

This lecture was a part of the Genomics and Personalized Medicine Forum sponsored by the Duke Institute for Genome Sciences and Policy (IGSP).

Physicians and Patients Make Best Decisions Together

November 27th, 2012

By Nonie Arora

Imagine yourself in this patient’s situation. You have just found out you have cancer, and the next phrase out of your doctor’s mouth is “You’re going to die with this cancer rather than of this cancer.” Which word do you think will jump out of that sentence? “With”? “Of”?

My money is on “die.” – Modified from Critical Decisions, pg. 99

Critical Decisions, Courtesy of www.peterubel.com

In Critical Decisions, Peter Ubel describes a common situation of a urologist explaining a prostate cancer diagnosis to a patient. In this exam room, the physician and the patient are on two different wavelengths. The doctor is trying to assuage the fears of the patient but is emphasizing technical details about the patient’s condition without first relating to the patient’s emotional shock from hearing a cancer diagnosis. Ubel suggests even a small acknowledgement of the patient’s emotional state could improve the situation. For instance, saying “I know it feels awful to be told you have cancer, but you should know that your cancer is curable. We can treat this.” (Critical Decisions, pg. 100)

Ubel, a Professor of Business Administration and Medicine as well as Public Policy, recently published Critical Decisions: How You and Your Doctor Can Make the Right Medical Choices Together. In the book, he explores how the rise in patient empowerment has left many patients confused and physicians unprepared to appropriately partner with patients in making medical decisions.

“My background in clinical medicine, ethics, and behavioral sciences collided. That led me to an in-depth investigation of patient preferences in medical care,” says Ubel. While his ethics background left him sure that patients have the right to ultimately decide their own medical care, he wanted to use his understanding of behavioral economics to uncover how physicians can best help patients make the decisions.

Peter Ubel, Professor of Business Administration and Medicine and of Public Policy. Courtesy of Duke Today.

Ubel also comments on how some emotional desensitization is essential to practicing medicine, and how desensitization can involve medical humor. He says that sometimes physicians “need to step back and laugh at situations, but the danger is we don’t want to laugh at patients.”  He suggested a way to combat the negative aspects of desensitization is to discuss ethical issues during the 3rd year of medical education, when future physicians are being exposed to the realities of medicine through hospital rounds.

He says the bigger worry is that aspiring doctors start off with the right attitude, but beliefs and practices erode through training and practice as physicians. In the current medical system, physicians have many patients and very little time, so doctors can get into bad habits. However, he says that good communication doesn’t take more time – it just takes retaining the right skills. Ubel advocates for physicians to ask patients to explain back what they have understood to get a better idea of patient understanding.

One of Ubel’s next big challenges is studying how cost factors into patient empowerment. Discussions about cost can seem taboo or uncomfortable in the exam room, but costs certainly factor into many health care decisions.

The strength of Critical Decisions is Ubel’s multidimensional perspective: he presents facts from research studies in several disciplines and compellingly (even humorously) draws upon his experiences as a physician, patient, and family member of a patient.

Here’s a link to an excerpt from the book for more!

When the Genome Gets Personal

November 15th, 2012

By Nonie Arora

It has been almost ten years since the first draft sequence of the human genome was completed in 2003, and some patients are starting to see benefits in clinic.

Dean Nancy Andrews

Dr. Nancy Andrews, Dean of the School of Medicine, recently spoke to undergraduate students about “When the Genome Gets Personal” over a hearty dinner of chicken stuffed with goat cheese, rice pilaf, and caramelized brussel sprouts. She was the latest guest in the 2012 Chautauqua West Lecture Series.

Andrews explained how DNA sequencing analysis can lead to a new diagnosis for patients. Even if the disease is not treatable, a diagnosis can mean a lot to patients and families, said Andrews.

“We are pushing boundaries between taking care of patients and doing research. The lines are blurry,” she said. Researchers want to sequence patient DNA to find causes for genetic diseases and, at times, to help individual patients who don’t have a diagnosis, according to Andrews.

She said it is easy to find variations in DNA sequence, but much, much harder to know how to interpret the changes. One of the tricky situations researchers face is telling parents or patients what they have found when they are not certain of the finding’s significance. She chairs a committee at Duke that is working on standards to help guide researchers to know what to report and how to design informed consent forms.

Andrews said DNA sequencing is already being used in clinical care: about $5 billion a year is spent on clinical sequencing. However, this sequencing is highly focused on genes relevant to the clinical situation; insurance companies will not yet support exploratory whole-genome sequencing. Andrews pointed out that there is a potential for exploitation by private for-profit companies with DNA sequencing capability, which may overstate their claims or capabilities.

Complicated scenarios can arise when sequencing is done in families. Among other issues, “There is a very real possibility of learning dad is not the biological father,” Andrews said.

Example of a pedigree generated from discussion of family history with patients, modified from Wikimedia Commons

Andrews said that clinical geneticists are going to need algorithms for interpreting sequence data and standard principles for revealing information for patients. These are under development at Duke and across the country.

Ultimately, Andrews thinks that personalized medicine “shouldn’t just be about genetics and genomics but [it should] also incorporate many other types of clinical data, including imaging studies and patient preferences, as well as a deep understanding of environmental factors.”

 

 

New Technologies Threaten Cognitive Liberty

November 15th, 2012

By Nonie Arora

Nita Farahany, Duke Law School Professor

Where do we draw the lines when it comes to new technologies in neuroscience?

Duke Law professor Nita Farahany is setting out to answer this question through an exploration of something she calls cognitive liberty. She spoke to a crowd of physicians, nurses, faculty members, and students at the last Trent Center Humanities in Medicine Lecture Series event.

“What does it mean if our conscious awareness of making a decision happens after the decision has already been made by our brains? Does that tell us anything about the concepts of responsibility or freedom of thought?” Farahany asked.

She doesn’t buy into the idea that we are absolved of responsibility because we are essentially predetermined machines, even if scientists like Benjamin Libet have shown that there is brain activity before conscious awareness. She argues that although some things are predetermined, we still have the flexibility of choice. For instance, having many fast-twitch muscle fibers may be a precondition of becoming a world-class track athlete, but the choice remains of whether to train extremely hard to reach the goal.

“We are more than preprogrammed bits and bytes,” Farahany said. Under the assumption that we retain flexibility of our thoughts, Farahany is exploring how those thoughts ought to be protected.

Although neuroscience is still in its infancy, it holds the potential to detect and tamper with memories, she said. But she hopes to explore what types of rights we ought to retain and what limitations there ought to be on the technology.

Farahany said that the mind might hold a lot of information that is very valuable to the government and to businesses. She pointed out that our brains can uniquely identify speakers and sounds. New technologies could detect this information, which could be very valuable to a criminal investigation. But it is it permissible to detect our recognition of objects or people?

Eyewitness testimony has a high rate of falsity and sometimes witnesses lack memories of key information. However, what if false memories could be planted in eyewitnesses easily? Most people would agree that it would be impermissible for the government to create its own “star witness,” Farahany maintained.

Propranolol, a beta-blocker that may stop consolidation of fear. Courtesy of Mind Disorders

While many may worry about enhancement of selves or memories, diminishing memories is another concern. The drug propranolol, a beta-blocker, has significant promise for people who have suffered from a traumatic experience because it can block consolidation of fear, said Farahany. For instance, rape victims who take propranolol may be less likely to develop post-traumatic stress disorder. “When given the opportunity to intentionally diminish experience of an emotion, should [people] be able to do so?” she asked. Compensation through the tort system is based upon the degree of suffering. Would the compensation for a victim of a rape be decreased by using the drug? Alternatively, do victims have a responsibility to reduce their own suffering by taking the drug?

There are many more questions to answer, and Farahany hopes to do so with her framework of cognitive liberty that considers the pillars of self-determination, consent, freedom of thought, and risks and benefits to individuals and society when deciding where to draw the lines.

 

Stem Cells Raise Tricky Questions

October 8th, 2012

By Nonie Arora

Medicine is about more than difficult diagnoses and cutting-edge research. Research and treatments often raise tricky moral questions.

Jeremy Sugarman Credit: Berman Institute for Bioethics

Dr. Jeremy Sugarman, the founding director for the Trent Center for Bioethics, returned to campus last week to give a talk on the ethics of stem cell research and treatment for the Humanities in Medicine Lecture Series.

“Stem cells are a hot topic that have captured the imagination of people around the world,” he said.

“Is it better to use leftover embryos from IVF or to create them for research?” Sugarman asked. He said there is little consensus on this issue, and the question remains whether there is a moral distinction between discarded embryos or those created for research purposes. There is also the thorny issue of whether it is morally acceptable to destroy embryos to create human embryonic stem cells, said Sugarman, who is now at the Berman Institute for Bioethics at Johns Hopkins University.

Amidst the controversy surrounding the moral status of embryos, there has also been scientific controversy within the stem cell field. Sugarman spoke of Hwang Woo-Suk, who claimed to have cloned human embryos and extracted their stem cells. However, his data was fabricated, Sugarman said. Sugarman elicited laughs from the packed audience when he joked about Woo-Suk’s former title “Supreme Scientist of Korea,” an honor that was later revoked. The laughter was tempered by the understanding of how unethical it is to fake any research, but especially on this scale. Still, Sugarman says Woo-Suk’s example serves to show the effectiveness of peer review in realizing false claims.

Human Embryonic Stem Cells. Source: "Follow the Money – The Politics of Embryonic Stem Cell Research." Russo E, PLoS Biology Vol. 3/7/2005, e234 http://dx.doi.org/10.1371/journal.pbio.0030234

Another issue many people are concerned about are chimeras – organisms that have parts from two different genetic lines. Already, bone marrow transplants create human-to-human chimeras, Sugarman explained. Some people have qualms about combining materials from human and non-human animals.

Other countries differ from the U.S. in policies on what can be done with human embryonic stem cells. For instance, in Germany it is a criminal offense to destroy an embryo to create a human embryonic stem cell line. It is also illegal for a German citizen to do such work abroad, Sugarman said. He brought up this point to illustrate why local oversight within academic institutions is necessary to not only make sure that research is “ethically and scientifically sound” but to also be certain that researchers are being protected.

Ethics in delivering care is equally important. “The desire for access to investigational treatments abounds, especially for devastating disorders,” according to Sugarman. But this is no reason for unsafe treatments to be delivered to patients. “It turns out some stem cell-based interventions are being delivered to patients without sufficient published data regarding safety or efficacy,” he explained.

Ultimately, scientific and commercial interests will be considered along with the hopes of patients and politicians when it comes to stem cell research and treatments, Sugarman said.

Crossing the Valley of Death

October 3rd, 2012

By Nonie Arora

David Adams shared his concerns about the output of America’s drug development pipeline at last month’s Science and Society Journal Club at the Institute for Genome Science and Policy (IGSP).

When it costs more than $1 billion to bring a drug to market with many failures along the way, “many (drug) companies are focused on de-risking,” according to Adams, an Associate Professor of Medicine in the Division of Medical Oncology.

Adams said the pharmaceutical industry seems to be counting on biotech companies and academia to help drugs cross the “Valley of Death” in anticancer drug development, but that has yet to happen.

While the rate of publication and quantity of scientific data continue to increase rapidly, not enough funding is being devoted to the “translational” research, which helps an idea make it from the lab to the clinic, Adams said.

Example of a tissue chip project sponsored through NCATS to improve drug safety. Credit to NCATS website.

The pharmaceutical industry has cut down on translational research, Adams said. Essentially, companies don’t want to take on projects unless they have a very high probability of success.

He also said that the National Institutes of Health (NIH) is generally risk adverse and tends to fund projects that represent “the next logical step,” rather than going for higher-risk, but potentially higher-gain ideas. The National Center for Translational Sciences (NCATS), established by the NIH director Francis Collins last year, is a promising step, Adams said.

When researchers design their cancer studies, many times they “don’t really take into account tumor physiology because we live in this era of molecular biology,” Adams said. He believes accounting for tumor physiology is very important. For example, doctors are rarely able to monitor how much drug makes it to a tumor, but translational research could solve this problem, said Adams.

Adams said drug development is also hampered by a human tendency toward  “technological lock-in.”

 

Personal Genome Machine Sequencer Credit: Benchmarks, a publication of the National Cancer Institute

“Why do we not change the way that we do things when there is compelling evidence to do so?”  He argued that:

1) people resist change in research and clinical environments because they are creatures of habit and convenience,

2) academics and clinicians often operate in silos rather than multidisciplinary teams that would enhance communication, and

3) we are obsessed with technology, as evidenced by genomics.

Adams said a new area to watch out for is theranostics: compounds that combine a therapeutic and diagnostic in the same formulation. Another area is miniaturization of electronics to permit real-time measurement of drug activity in and around tumors. An implantable radiation dose monitoring system is already commercially available and implantable sensors for management of diabetes are in the pipeline.

Ultimately, greater emphasis on translational research and breaking technological and organizational lock-in may help us cross this “Valley of Death,” he said.

Igniting U.S. health care’s ‘escape fire’

September 21st, 2012

The film Escape Fire explores what's fanning the flames of the health care debate. Credit: escapefiremove.com

By Ashley Yeager

Imagine lighting a match to protect yourself from the flames of a fire.

It’s probably not the first thing you would think to do to stop from being burnt. But when there’s no other escape, the technique works. In 1949, Robert Wagner Dodge became living proof when he lived through the Mann Gulch fire by setting his surroundings on fire.

Now, his actions have become a metaphor for drastic ways government and industry should change U.S. health care before it too burns everything in its path.

Escape Fire: The Fight to Rescue American Healthcare showcases the health care system’s metaphorical blaze. The award-winning documentary, described as the “Inconvenient Truth” of the health care debate, opens nationwide in October. But members of the Duke community saw it for free on Wed., Sept. 19. They were also able to participate in a post-film panel discussion, which fleshed out a few potential escape fires for the health care industry.

“I think working with one patient at a time can help everyone become healthier,” said Annie Nedrow, a primary care physician and the associate director of Duke Integrative Medicine, which sponsored the event. But as the film points out, the current system rewards doctors for the number of patients they see, not the amount of time they spend with each person or the plans they may develop to help that patient prevent and manage disease.

Ironically, almost 75 percent of health care costs are spent on preventable diseases. The film, directed by Matthew Heineman and Susan Froemke, illustrates this statistic through anecdotes, where a band-aide, pill or even invasive surgery, such as inserting a stent to relieve heart blockages, provides immediate relief but does nothing to address the underlying causes of illnesses – typically diet and lifestyle.

Preventable diseases are 75% of our health care costs. Credit: escapefiremovie.com

“There’s got to be a shift in our culture, one where we actually have access to safe parks to exercise, healthy food, and the time to eat it,” said Adam Perlman, Duke Integrative Medicine’s executive director. He also agreed with Nedrow that a new system should invest more in primary care and health promotion, rather than disease treatment.

To set an example and test the feasibility of such a system, Duke Integrative Medicine has opened a primary care practice that limits the number of patients each physician sees so the doctors can spend more time with each patient and create a more holistic approach to that person’s health.

Perlman said that health coaching could be another important aspect of correcting the healthcare system. He explained that doctor X might tell a patient to lower his blood sugar, doctor Y then tells him to lower his blood pressure, and all the patient really wants to do is dance at his daughter’s wedding. “A health coach helps the patient reach those bigger goals by connecting the dots and helps them execute the plan to get there,” he said.

The film and remarks prompted many audience members to question what it would take to change the current system. Nedrow, who said she has been inspired by books on creativity and innovation, suggested that it was dialogues like the one they were having that could ignite change to repair the broken model of health care or create a new system.

More innovation, however, may mean that more people need to step into the fire and strike a match, rather than run and try to dodge the flames.

Football Player Makes an Impact

September 19th, 2012

by Ashley Mooney

One Duke football player is making an impact, both on and off the field, on the health of his teammates.

Senior Conor Irwin, an evolutionary anthropology major who is also an offensive lineman on the varsity football team, has done research regarding joint replacements and athletic injuries during his time at Duke.

In summer 2011, Irwin worked at the K-Lab, which focuses on understanding and preventing athletic injuries. There, he studied pressure distribution on the foot during unanticipated cutting—a maneuver where the person changes directions quickly.

To test this, subjects wore pressure sensor insoles in their shoes to show the distribution of stress in their feet during the task, which involved running in a straight line and then planting and cutting in the direction of a flashing light.

Irwin also collected data on hip, knee and ankle replacement patients who came into the lab for evaluations.

“As I understood it, Duke is one of few institutions to perform ankle replacements, and this [data] was being used to evaluate the different surgical techniques for ankle replacement,” Irwin said.

Beyond his work in the K-Lab, Irwin conducted an independent study with the advice of Dr. Claude Moorman III, director of the Duke Sports Medicine Center and head team physician, and John Anderson, a sports medicine fellow. He reviewed different surgical techniques for repairing a ruptured medial collateral ligament in the knee.

“The frequency of MCL injuries in football players—particularly offensive linemen, which is what I play—made me interested in a project dealing with the MCL,” he said.

MCL ruptures do not often require surgical interventions, however, there are certain cases where it is necessary. Irwin studied the progression of MCL treatments as well as current techniques.

Although the paper is still in the editing stage, Irwin noted that they plan to submit it to the Journal of the American Academy of Orthopaedic Surgeons. They will also submit a video of an MCL operation on a cadaver as a separate publication.