Medicine | Duke Research Blog

Everyone Makes Mistakes

April 24th, 2013

By Pranali Dalvi

Dr. Brian Goldman, Credit: nsb.com

“Every important thing that I have ever learned since the day I was born has come from a mistake,” said Dr. Brian Goldman on April 17 during the Duke Colloquium.

Goldman is a renowned thinker and leader on issues of medical ethics and medical error. He has had great success in two high-adrenaline fields: broadcasting and medicine.

Not only is he a practicing emergency physician at Mount Sinai Hospital in Toronto but he also hosts an award-winning radio show White Coat, Black Art where he discusses the Canadian healthcare system. His bold TED Talk ‘Doctors Make Mistakes: Can We Talk about That?’ has over 700,000 hits.

Goldman’s life-altering mistake happened during a 2-month elective in neurology at Johns Hopkins. By medical school, he was a veteran insomniac, often waking up early — except for the one morning he was supposed to deliver grand rounds. That morning, he woke up at 10 AM, the exact moment when he was supposed to be presenting rounds in the neurology conference room at the hospital across the street.

“This mistake was a dramatic enough gesture to make me pay attention. I don’t wish a medical error on anybody, and I don’t wish the misfortune that happens to patients and families that are directly involved. But sometimes it’s a moment like that which redirects you and gets you into thinking about what you need to do with the rest of your life,” Goldman said.

The mistake made him reconsider neurology.

Credit: thestudentceo.com

Too often people have one of two worldviews of failure. The first inspires you to do better – if you fall down seven times, get up eight. The other shows success and failure as completely different paths.

“What we need is for health professionals and the public to realize that mistakes are inevitable with humans,” Goldman said.

What does error look like in medicine?

Radiology mistakes including X-ray and CT misinterpretations, miscalculating medication dosages, and hospital-acquired infections due to poor hand washing practices are human errors in medicine. All potentially catastrophic yet hard to detect.

Why do these errors happen?

The vast majority of health professionals are some of the most caring and compassionate individuals. Why do they mess up? Emphasis on quantity over quality, stress, miscommunication and messy handwriting are just a few of the many reasons.

“I spoke to a pharmacist who said that if you simply add 30 seconds of look-up time to every medicine dispensed at the hospital pharmacy, he’d have to hire 2 more full-time pharmacists. If you don’t have that kind of money, this is the sort of institutional cutting of corners that we have to go through to make ends meet,” Goldman said.

Credit: The Adventures of Pam & Frank Blog

Errors also result from the organization of the system. Residents often don’t go home despite 80-hour week regulations. They fear that no one else knows their patient as well as they do. Patient safety is also compromised as you increase the number of handovers due to duty hour regulations.

Goldman insists on the development of technologies to prevent mistakes, reducing responsibilities to allow increased productivity and fostering a loving and respectful environment for doctors to discuss their errors.

How can we aim for success in a field where failure is so effortless?

The Duke Colloquium, the brainchild of Dr. Andrew Hwang, is a university-wide initiative to pull the humanities into the professions. The event bring forward-thinking visiting scholars to Duke’s campus to inspire students, faculty, and the broader Duke community to become more socially conscious professionals.

Student Profile: Arnab Chatterjee

March 28th, 2013

By Nonie Arora

Arnab Chatterjee, Duke Student. Credit: Chrislyn Choo

Freshman Arnab Chatterjee, Credit: Chrislyn Choo

Freshman Arnab Chatterjee spent three days in Abu Dhabi developing solutions to health care problems plaguing the Middle East. He travelled to the Global Issues Network conference, hosted by New York University in Abu Dhabi.

The conference pushes undergraduates to develop sustainable action plans to solve global problems on a regional level in just three days. It has a broad reach, from energy, to health, to waste management. The plans are intended as stepping-stones to bringing positive change to the region.

Chatterjee’s small group focused on mental health, which is often disregarded as a legitimate health concern in the Middle East.

“The ruling bodies of the UAE don’t acknowledge that mental health issues are a real problem, so it often gets swept under the rug,” Chatterjee said.

The group initially attempted to avoid a direct discussion of mental health by asking patients about irregularities in their sleeping and eating patterns, which can be early indicators of mental health issues.

Chatterjee’s team discovered that diabetes was one of the top contributors to the UAE’s mortality rate, and an issue that the government was very much invested in addressing. Multiple studies have suggested a correlation between an increase in the rate of depression among diabetes patients, and vice versa. Other work has shown that the mortality rates among patients with diabetes and depression are significantly higher than those with just diabetes, Chatterjee said. But in this region, seeking help for a mental illness is highly stigmatized. Addressing depression by targeting diabetic populations and their families alleviated this stigma somewhat.

Near the end of the conference, his team suggested that a clinical research study be conducted by New York University’s public health institute in the region to address whether patient-family support specialists could be helpful in improving patient outcomes. They planned to screen for depression, but without describing the behavior by name. “People can be offended even by doctors asking questions that imply a patient has depression. It’s a delicate balance between being tactful but remaining effective,” Chatterjee said.

Chatterjee and his team presented their plan to health care providers from Cleveland Clinic’s medical center in Abu Dhabi, government officials, and the press in Abu Dhabi. He said it was well received by most, but that the government officials remarked that they would have preferred even less emphasis on mental health issues.

Beyond this specific project, Chatterjee said that attending the conference gave him a great opportunity to build a global network with other undergraduates with diverse interests. He is interested in medicine and research, works as a research assistant in the Nicolelis Primate Laboratory, and will be working as a Howard Hughes Research fellow this summer.

Making sense of smells

March 18th, 2013

By Prachiti Dalvi

Nobel Laureate Dr. Richard Axel, who visited Duke on March 14, 2013.

“A good scientist has to have a nose for which field to work in,” cancer researcher Bernard Weinstein once told his mentee Dr. Richard Axel.

It was a saying Axel took quite literally.

He and Linda Buck won the 2004 Nobel Prize in Physiology or Medicine for discovering the cell receptors that run our sensory system for olfaction, or the sense of smell.

Axel first stepped into the research world when he took a job as a glass washer to support himself during his undergraduate years at Columbia University. After a few broken test tubes and dirty beakers, he was fired as a glass washer and, instead, rehired to do research. He went on to publish three papers as an undergraduate, including one where he was senior author.

In 1979, he earned his medical degree from Johns Hopkins University. He then returned to Columbia, and in 1977 he, along with Michael Wigler and Saul Silverstein, discovered a way to insert foreign DNA into a host cell to produce particular proteins.

The finding grew into to the field of molecular cloning and earned Axel a spot in the National Academy of Sciences at 37.

Axel moved on to study how the brain represents the external world. This is a central issue in philosophy, psychology and neuroscience. But unlike, vision and touch, which have at least two dimensions in the external world, information about odors has no dimensionality at all.

So, how is smell represented in the various smell centers of the brain? Axel explained what scientists know about the representations during a March 14 lecture sponsored by the Ruth K. Broad Foundation and the Chancellor’s Lecture Series.

Pathway of odor perception (courtesy of nobelprize.org)

The process starts in the nose, where different kinds of smell-sensing cells line the nasal cavity. Each type of smell-sensing cell expresses only one of about 1400 odor-receptor genes. The cells expressing a given gene are randomly distributed through the nasal tissue and send projections back through the skull into the olfactory bulb.

This bulb is essentially first relay station for sensing smell in the brain. The incoming information gets consolidated in a part of the bulb called the glomerulus. There a given odor receptor activates nerve fibers called glomeruli. They send signals to higher brain regions, which then create a topographic map of incoming odors.

This topographic map is similar, or conserved, in all individuals of a species, Axel said.

His lab at Columbia is now focused on understanding how the sense of smell is established during development, how it may change over time and how certain smells can elicit specific thoughts and behaviors.

Summer camp inspires allergy research

March 5th, 2013

By Ashley Mooney

Courtesy of Nicole Leung.

For some undergraduates, research ideas stem from summer camp.

Junior Nicole Leung, a biology major concentrating on pharmacology, is doing an independent study on allergies and pediatric immunology. She works in Dr. Wesley Burks’ lab at the University of North Carolina in Chapel Hill and explained that her interest in allergies first started when she was a volunteer at a summer camp.

“I was taking care of a little boy who was allergic to so many foods and he had to carry an epi-pen around with him all the time,” she said. “It was my first exposure to such a serious problem with allergies.”

“It was really hard for me to see a boy who was so close to being normal be completely abnormal during camp,” she said, adding that because of the boy’s severe allergies, he was very shy and had a hard time making friends.

Leung saw the challenge of severe allergies again in college when a gluten allergy started to affect her freshman-year roommate.

Now, Leung is trying to understand whether people can develop a long-term tolerance to food allergies, even though there is currently no cure for allergic diseases. The lab is also developing immune-system therapies to sensitize patients to allergens and see how long they can withstand the allergic effects.

“Very little is known about allergies, but they tell a lot about our immune system,” she said, adding that “as the human population grows, I think that allergies are going to be a major concern in the future, so this field has great potential.”

In Leung’s previous research, she compared several allergy tests to find which best predicts the severity of allergic reactions. Most common allergy tests, like the skin-prick test and the blood-based ImmunoCAP test, do not determine how severely people may be allergic to certain substances.

Courtesy of Nicole Leung.

“They only will tell you that you’re allergic but you might not have a reaction to it,” she said.

Using a statistical analysis, Leung found that the basophil activation test has a much higher correlation to severity than the skin-prick or ImmunoCAP tests.

“With the basophil activation test, we mix allergens in blood and try to see whether a certain allergen will cause basophils to degranulate and release histamines, which is what triggers the allergy symptoms,” she said. “Because these activated basophils expose CD63 molecules on their surface, we can determine the percentage activated and use cutoff points to identify whether the person is allergic.”

She added that the test only requires a small amount of blood and is a relatively quick procedure. But there are still questions of how it can be applied to clinical practice.

For Leung, the hardest aspect of research is digging through background information to find out how to move her project forward.

“None of the articles point you to a clear answer, and that is the most challenging part of research. But it is also the most exciting part because you get to test your own hypotheses,” she said.

Besides her allergy research, Leung also works in a neuroeconomics lab that looks at risky decision-making in gambling. The lab uses eye trackers to measure how much a test subject’s eyes dilate and how often they shift their eyes between two choices—one risky option, and one safer one.

Although Leung said she has a more direct role in the design and implementation of her allergy research, she said she enjoys meeting and interacting with the families who participate the neuroeconomics study.

Thinking Beyond the Grave at Duke-UNC Bioethics Symposium

February 26th, 2013

By Nonie Arora

Duke student Meredith Rahman is intrigued by how we justify treatment of the dead for the sake of science. She asked her audience at the Duke-UNC Bioethics Symposium: How can we interact with human remains in an ethical way?

Duke Student Meredith Rahman Presents at Duke-UNC Bioethics Symposium. Credit: Nonie Arora

Rahman began the discussion by explaining how bodies are obtained for use after death. “Historically, there was great fear about grave robbings to further science,” she says, “but that has since calmed down.” Now, many bodies are obtained through donation, and we legitimize the use of bodies through prior consent when the subjects are still alive. In the 1980s however, the Body Farm in Knoxville, TN took unclaimed bodies from medical examiner’s offices to study decomposition, she added.

Rahman discussed what can happen when we can no longer speak for ourselves. There can be tension between the wishes of the deceased and wishes of the family members, and it can be hard to give a voice to those who have already passed away. This is similar to situations in which family members may override do not resuscitate (DNR) orders, Rahman clarified.

There’s a further issue of consent even when a person has signed a donor card to say that they want to donate their body to science: they don’t always know how their body will be used. “It could be an undergraduate student, such as myself, going into the lab and learning basic anatomy, or it could be an MD practicing a specific surgical skill. But when you consent to donate your body to science, you no longer have a say over what happens,” she said.

A plastinated human body exhibited at the Body Worlds show, Museum of Natural History, San Diego, 2009. Credit: Wikicommons. Photograph by Patty Mooney, Crystal Pyramid Productions, San Diego, California.

Some exhibits transform human remains for science education, such as the Body Worlds exhibit, according to Rahman. Body Worlds relies on a technique called plastination, which essentially turns human soft tissue into plastic. The result is a body that is about twenty percent human materials. She said that while these bodies can be effective teaching tools, there are ethical considerations, especially when commercial interests are involved and the primary purpose is public viewing rather than scientific development. The audience was shocked to hear that “slices of human” are available for purchase.

Rahman’s presentation was part of the Duke-UNC Bioethics Symposium, Ethical Frontiers in Research, a student-run conference developed by the Duke Undergraduate Bioethics Society (DUBS) and Carolina Bioethics Scholars (CUBS). This year, the organizations have received funding from the Kenan-Biddle Partnership grant as well as the Kenan Institute for Ethics and the Trent Center for Bioethics, Humanities & History of Medicine. As part of the Kenan-Biddle partnership, they are hosting an ongoing series of dinner discussions on bioethical topics. The next event will be hosted by UNC on Feb. 28; Dr. Steven Gray will discuss how gene therapy clashes with traditional pharmaceutical business models.

As an executive board member for DUBS, I am excited to continue our collaboration with UNC students. Although basketball rivalries may pull us apart, last weekend we found that lively ethical conversations can bring us together.

Blasting away glioblastomas

February 21st, 2013

By Ashley Mooney

The purple area of this brain is a glioblastoma tumor.

Some undergraduates get to see the fruits of their lab labor early in their careers.

Junior Anirudh Saraswathula, a biology major and neuroscience minor, has been doing research at Duke since his first week on campus.

He started as a work-study student in professor of cell biology Blanche Capel’s lab, but said the basic sciences were not his true passion. Now, Saraswathula works on translating basic research with the Duke Brain Tumor Immunotherapy Program.

“A lot of what I do in the lab involves looking at protocols that are used in basic science research and trying to apply them to what we’re doing here,” he said. “So a lot of it is going to be culturing cells from patients, and then doing a variety of tests depending on what it is that I want to do.”

He is currently studying immune-system therapy for glioblastoma, a type of malignant brain tumor. By reprogramming a patient’s T-cells, researchers can direct the immune system to fight glioblastoma. Although Saraswathula was not involved in developing the treatment, he is working to evaluate the treatment’s mechanism and its long-term effects on the immune system.

“One of the reasons that brain tumors are so devastating (with treatment they can extend survival to about 18 months) is that they’re just so recurrent,” he said. “These types of tumors also change who you are as a person because of where they happen.”

Saraswathula’s day-to-day work involves culturing tissue, using flow cytometry — a technique used to sort cells, detect biomarkers and engineer proteins — and PCR, which copies DNA.

Saraswathula is also studying the quality of T-cell responses to different clinical trials and understanding whether certain types of B-cells are repressing the function of the tumor vaccine.

“Those projects are focused on future trials. How can we improve, how can we modify these therapies to better improve the immune system’s response in order to fight these tumors,” he said.

Although he began his research just for the experience of doing it, Saraswathula said that applicability is now what is most important to him.

“If I discover some obscure gene in stem cells, there’s not going to be any real application there for maybe 30 years,” he said. “With my current research, if I find something, [in] the next trial a few years from now, there will be a patient getting the drug, and I would have had a contribution to that.”

Finding Consciousness

February 21st, 2013

By Nonie Arora

Brain scans of various disorders of consciousness. Credit: Wiki Commons

Can we be certain whether a patient is minimally conscious or in a persistent vegetative state?

What kinds of rights do minimally conscious patients have?

How should minimally conscious patients be treated?

Scientists, ethicists, lawyers and physicians asked these questions at the Finding Consciousness workshop at Duke in January 2013.

Recently, neuroscientists have devised methods to detect consciousness in patients with severe brain injury who may not appear to be aware of themselves and others. But as the science develops so do new ethical dilemmas.

Patients with severe brain injury are often written off, despite growing scientific evidence of potential improvement, said Joseph Fins from Cornell University. Fins gave the annual Nancy Weaver Emerson Lecture sponsored by the Trent Center for Bioethics, Humanities & History of Medicine as part of the workshop, and he focused on the application of neuroethics to the minimally conscious state.

Fins believes that family members of patients are often forced to make decisions about withholding or withdrawing care without complete, understandable information. They are compelled to consider organ donation, even prematurely. In his work, Fins interviews family members of brain injury patients. In one conversation, a mother of a patient described an interaction with a neurologist who called the patient “basically an organ donor now” and said, “He doesn’t have the reflexes of a frog.”

Then, the neurologist urged the mother to consider organ donation — all within 72 hours of the injury. Fins called for patients and family members to be treated with more sensitivity and respect.

Jeremy Fins. Credit: Trent Center for Bioethics, Humanities, and History of Medicine

The vegetative state has been seen as medical futility, and the paradigm was “once you’re vegetative, you’re done,” Fins said. However, physicians in the field have begun to see families and patients who have looked vegetative, but then suddenly showed some level of response to stimulus.

While some patients become permanently vegetative, others can become minimally conscious, Fins said, referencing a study where about 40 percent of patients who were diagnosed as vegetative were actually minimally conscious.

“This is unconscionable, but that’s where we are,” he said, adding that much of the disparity could come from disinterest, neglect and marginalization of these patients. People would not accept this level of misdiagnosis in cancer or diabetes care, he said.

It is our obligation to give voice to minimally conscious patients as a basic civil right, Fins said, especially as better methods of identifying these patients and stimulating recovery are likely to come in the future.

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).