By Rob Mitchum

When a doctor pulls a notepad out of his or her white coat, you might expect them to be writing down a drug prescription. But a recently completed contest thrown by the Prizker School of Medicine suggests that physician might be scrawling down a few lines of verse as well. The first annual Pritzker Poetry Contest received an overwhelming response, with more than 80 poetic submissions from Pritzker students, faculty, and residents. Those nominees were whittled down to 11 finalists, and the top entries in two categories were announced last week.

The idea to tease out the poetic side of physicians originated with Rama Jager, an assistant professor of opthamology & visual science with the University of Chicago Medicine. Jager saw a story in the New York Times about similar contests at the Yale and University College London medical schools, and thought that the concept would help students and faculty here express their feelings about their work and their relationships with patients.

With the help of medical students Rebecca Levine and Margaret Nolan and faculty advisor Shalini Reddy, the first Pritzker contest was born in February. Participants could submit a poem in either the rules-free open verse category, or (inspired by another New York Times article), the six-word poem division, a chance to express one’s feelings in highly efficient fashion.

“We wanted to have two different categories, especially since students, residents and doctors are often so busy that an open-form poem can be daunting to take on,” said Nolan, a fourth-year Pritzker student. “6-words can be easier, and yet challenging in other ways as it forces you to distill an experience or thought into so few words. It’s a really fun exercise for anyone to try, though, and we’ll hopefully experiment with other original forms in the coming years.”

The missions of the contest — to “recognize and celebrate the humanistic side of medicine at all levels of medical training and practice” and “foster continued compassion for our patients, enhancing the therapeutic doctor-patient relationship throughout our medical careers” — inspired a flood of replies [pdf]. Generous prize money, which ranged as high as $1,000 for first place in the open poem category, surely didn’t hurt too. Levine said that the final totals doubled the organizers’ original estimate, and gave the panel of 13 judges plenty to work with.

“We thought that there would be around 15 to 20 entries in each category given that this was the first year of the competition and people may not have seen our messages about the competition, have had time to write poems, or be interested in this form of expression,” said Levine, also a fourth-year with Prtizker. “When we received around 40 poems in each category, we were shocked and elated!”

The winning poems, which can be read in full and properly formatted form at the Pritzker website, are a deft blend of medical terms and emotional verse. You may not see the phrase “sinus tachycardia” appear in too many poems published in Granta, but the first prize winner in the open-poem category, H.I.E. by third-year medical student Joshua Williams, weaved that term and other pieces of physician lingo into an artful description of a two-year-old critically ill hospital patient.

You are G-tube, trach-dependent,
deaf, blind, devastated, orphaned,
forgotten,
and two years old today.

You are an incredible teacher.

Second-year Pritzker student Liese Pruitt’s Two Tiny Feet (tied for second) contrasts the bright environment of a delivery ward with a scene of mourning.

sanitized
unyieldingly,
cheerful, a place
for hellos, here
are only good-byes

And first-year Brian Thurber’s Monday Morning Rounds illustrates the all too routine struggle of providing emotional reassurance to patients whose health is declining.

It’s not fair for me to give her a false sense of
security
All the news is bad
Her numbers look worse than they did the day
before
I can’t lie to her
I can’t tell her that everything’s going to be ok
Because it’s not

It’s just not . . .

The transformation of such trying experiences into poetry can help doctors-in-training deal with their emotions and improve their bedside manner going forward, both Levine and Nolan said.

“I think that writing poetry helps foster compassion in medicine and stronger doctor-patient relationships in several meaningful ways,” Levine said. “The process of writing poetry allows you to reflect on your experiences with patients and remember moments where words, actions, or therapies helped alleviate patients’ suffering. By recording these moments, you will be better able to repeat these best practices when caring for patients.”

“Being a physician and witnessing human suffering with such intensity, and so frequently, requires periodic reflection in order to maintain our own emotional equilibrium,” Nolan said. “It also requires support from friends, family and colleagues. Poetry is one vehicle that fosters this, and allows us to communicate and share what we have experienced with others.”

And as the six-word poem winners demonstrated, you sometimes don’t even too much space to capture the enormity of clinical experience and medical education.

“They listened this time. Sans stethoscope” (Kunmi Sobowale, second-year)

“Doctors err. Great ones reflect, metamorphose.” (Yiuka Leung, fourth-year)

by Rob Mitchum

An advantage and disadvantage of hypothesis-free studies looking for genes associated with various traits or diseases is that they often point to genetic candidates that don’t make immediate sense. One example of this occurrence was the 2005 discovery of an association between the gene Glo1 and anxiety-like behaviors in mice. Previously, scientists knew Glo1’s protein product, glyoxylase 1, primarily as a enzyme involved in in glycolysis — the cellular digestion of glucose. Nobody had considered that glyoxylase 1 played a role in brain function, much less behavior, leading some to question the validity of the genetic association.

“When people discover a gene, they’re always most comfortable when they discover something they already knew,” said Abraham Palmer, assistant professor of human genetics at the University of Chicago Medicine. “The alarming thing here was there was a discovery of something that nobody knew, and therefore it seemed less likely to actually be correct.”

But Palmer’s laboratory continued chasing down the Glo1/anxiety connection, and their experiments paid off in the discovery of an entirely new mechanism for anxiety disorders. Their study, published today in the Journal of Clinical Investigation, also describes a previously unrecognized inhibitory neural factor, offers a promising new target for the treatment of anxiety disorders and other psychiatric symptoms, and suggests an intriguing connection between metabolism and neurobiology.

“What’s neat is that we started with exploratory, open-ended genetic studies in mice, and we’ve now gotten into some fundamental new physiology that nobody had appreciated or put together before,” Palmer said. “Now we’re starting to reap some of the fruit from those types of genetic studies to enrich our understanding of more classical aspects of biology.”

Lead author Margaret Distler, an MD/PhD student in the Pritzker School of Medicine, started her examination of the Glo1/anxiety link by testing it in a new way. In a 2009 paper, Palmer’s group hypothesized that mice with more copies of the Glo1 gene — a genetic phenomenon known as copy number variants — were more likely to show anxious behaviors. Distler tested this theory by inserting two, eight, or ten copies of the gene into mouse lines, and measuring their anxiety with various laboratory tests, including the open field test and the light-dark box test. As predicted, more Glo1 copies equated to more anxiety-like behavior, lending more evidence to the link.

“Animals transgenic for Glo1 had different levels of anxiety-like behavior, and more copies made them more anxious,” Palmer said. “We showed that Glo1 was causally related to anxiety-like behavior, rather than merely correlated.”

The next step was to figure out how Glo1 accomplished its unexpected influence. In glycolysis, glyoxylase 1’s job is to metabolize and reduce levels of a byproduct called methylglyoxal, or MG for short. So Distler tried an experiment so simple it almost obvious: if increasing Glo1 increases anxiety, would increasing MG levels alleviate it? After injecting mice with MG, the mice were less anxious in the behavioral experiments, suggesting that the metabolic byproduct does in fact play a role in anxiety — and a relatively fast role, at that.

“Methylglyoxal changed behavior within 10 minutes of administration, which means it’s a rapid onset. It’s not changing gene expression, and it’s not having long-term downstream effects,” Distler said. “That was our first breakthrough.”

A major clue to what MG was doing in the brain was provided by trying higher doses of the factor, which caused mice to become hypothermic and sedated — so much so that Distler couldn’t test their anxiety. Those symptoms are often seen with drugs, such as barbiturates and benzodiazepines, that activate receptors for the neurotransmitter GABA and are sometimes prescribed to treat anxiety. A collaboration with electrophysiologist Leigh Plant found that MG does in fact activate the GABA-A receptor, making it only the second endogenous factor (after GABA itself) discovered to have that effect in the brain.

Those findings led to a model for the role MG plays in the brain. In the synapse, higher levels of the neurotransmitter GABA would be expected to activate the GABA receptors on the receiving neuron. But away from the synapse,  MG might out-weight the influence of GABA, making it the most important inhibitory factor at these locations. Here too, the connection to glycolysis fits into the model, as more active neurons would ramp up glycolysis, producing more MG, which can then act as a negative feedback “brake” on neuronal activity.

“It’s well known that if neurons become too excited, intracellular calcium levels rise and the cell will die spontaneously,” Palmer said. “There are known mechanisms by which excessive metabolic activity can be toxic to neurons, so you would want to have a brake that would quiet the system down.”

That neurobiological brake might also provide a new target for the treatment of anxiety and other psychiatric conditions, such as epilepsy and sleep disorders, that are commonly treated with GABA agonist drugs. To test this premise, Palmer and Distler contacted John Termini of the Beckman Research Institute of the City of Hope, who had previously created a Glo1 inhibitor for an entirely different reason: the treatment of cancers where tumor cells over-express the Glo1 gene. Termini provided samples of the Glo1 inhibitor to the researchers, who tested its effects on mouse anxiety. As with MG treatment, inhibiting Glo1 successfully lowered anxiety-like behaviors, suggesting that a similar approach might be useful clinically for treating psychiatric conditions while minimizing the side effects of existing drugs.

“The GABA-A receptor agents already out there have a lot of side effects, such as sedation and hypothermia, as well as a high abuse liability,” Distler said. “It’s possible that taking a Glo1 inhibitor will increase only MG levels to a certain maximum. You could have the potential for more specificity, given that you’re activating a system that’s already in place, not just dumping methylglyoxal or some other GABA-A receptor agent throughout the brain.”

“It’s a different way of hitting these GABA-A receptors,” Palmer said. “We have yet to determine if that’s a better way of doing it, but it’s certainly different, and it gives us a unique angle of attack on this system and potential advantages that we have yet to evaluate.”

But the potential connection between metabolic activity and neuronal inhibition also presents a non-pharmacological possibility for affecting behavior. Activities that increase cellular metabolism, such as exercise or eating, could alter a person’s brain levels of MG, and thereby influence their behavior. Conversely, metabolic diseases such as diabetes may disrupt the factor, with previously unrecognized psychiatric consequences.

“This could also be an interesting system where a person or animal’s metabolic load reflects their neuronal inhibitory tone and behavior,” Distler said. “Maybe it’s not a drug, but it’s an interesting therapeutic approach or concept for how could we affect behavior by changing our metabolic state.”

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Distler, M., Plant, L., Sokoloff, G., Hawk, A., Aneas, I., Wuenschell, G., Termini, J., Meredith, S., Nobrega, M., & Palmer, A. (2012). Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal Journal of Clinical Investigation DOI: 10.1172/JCI61319

by Rob Mitchum

The brain is a privileged organ, afforded protections denied to all the other organs of the body. Though the circulatory system functions much the same way above and below the neck, using blood to exchange nourishment for waste with cells, the exchange is conducted under much heavier security in the central nervous system. This TSA for the brain and spinal cord is known as the blood-brain barrier, and its role is protecting the fragile, irreplaceable cells of the nervous system from external disease and the body’s own immune weapons.

While we can all be thankful for the unceasing service of the blood-brain barrier (sometimes abbreviated as BBB), many scientists are interested in figuring out how it can be breached. Many neurological diseases, including multiple sclerosis and stroke, can be attributed in part to breakdowns of the BBB. Drugs designed to treat brain disease must also find a way through the BBB’s strong defenses to get to their desired targets.

That made the blood-brain barrier the perfect subject for this year’s Chicago Symposium on Translational Neuroscience, an annual gathering of neurologists and laboratory neuroscientists from the University of Chicago Medicine and other institutions. This year, the Neuro contingent was joined by UChicago’s young Institute for Molecular Engineering in presenting the conference, underscoring that the topic is very much an engineering problem: how do you build a blood-brain barrier, and how do you selectively knock it down?

The day’s first speaker, Richard Daneman of the University of California, San Francisco, explained what the field currently knows about the unique properties of the BBB. In most of the body, the capillaries of the circulatory system are “leaky,” he said, allowing many molecules to pass between the cells and the blood through the cracks between the endothelial cells that make up the blood vessel walls. But in the BBB, those cells form a tight seal, and molecules are transported into and out of the vessels by highly selective transporters instead of passive diffusion. Daneman illustrated these defenses with an experiment where blue dye is injected into an animal, which is later dissected. While organs such as the kidney or liver take on a distinct blue hue, the brain and spinal cord remain free from the dye, which cannot penetrate the barrier.

Daneman is interested in “barriergenesis,” how the BBB is constructed during development. Previously, researchers hypothesized that brain cells called astrocytes were responsible for building the BBB. But using mice and rat models, Daneman’s laboratory determined that this defense system is already in place during embryonic stages, before astrocytes first appear. Instead, Daneman’s experiments pointed to another cell group called pericytes as critical architects of the BBB. When the genes for forming pericytes were knocked out in a mouse line, the BBB did not form its tight seal…as indicated by the appearance of blue brains after a dye injection.

Now Daneman’s lab is digging into the molecular signals that construct the BBB during development and maintain its integrity throughout life. Some of those experiments involve taking the endothelial cells that form the BBB out of their native habitat to study them on the lab bench, the subject of a talk from Eric Shusta of the University of Wisconsin - Madison. Endothelial cells only make up about one-tenth of one percent of the cells in the brain, Shusta said, and don’t form the tight seals characteristic of the BBB in the lab dish unless they are co-cultured with other neural cell types.

Shusta’s laboratory has tackled these problems using the hot prospects of laboratory science: pluripotent stem cells. When researchers in his group decided to try to differentiate stem cells into BBB-like endothelial cells, Shusta said “I thought they were a little bit crazy, but the initial experiments worked.” What’s more, with neural stem cells, the researchers could also generate other nervous system cell types that might play an important role in barriergenesis. That experimental set-up can now be used to test for the cellular factors that build the BBB and as well as assess different drugs’ ability to pass through the barrier, without the constraints of having to endlessly harvest scarce endothelial cells.

“From one rat brain we can get about 6 to 12 filters, but from one vial of stem cells, we can easily get ten thousands of filters,” Shusta said. “We think that we can keep optimizing this, and hopefully make an impact in developmental and drug screening applications.”

The clinical reasons for pursuing BBB research were described by Alexandre Prat, the head of neuroscience research at the Centre hospitalier de l’Université de Montréal (CHUM). A neurologist specializing in multiple sclerosis, Plat described how the autoimmune neurological disorder is caused in part by immune cells infiltrating the brain through gaps in the BBB. Prat’s research is focused on how these breaches occur during MS attacks, with a particular interest in cell adhesion molecules (CAMs), factors produced by the endothelial cells that act as chaperones to transport immune cells across the BBB.

The laboratory found that one particular CAM, called CD166/ALCAM, offers a promising target for preventing the immune cell infiltration associated with MS attacks. What’s more, it may avoid the rare but very serious side effect of another MS drug, natalizumab, which uses a similar strategy of blocking the passage of immune cells across the BBB. In approximately 1 out of 1,000 cases, natalizumab works too well, leaving the central nervous system open to infection by the JC virus, which can cause a fatal condition called progressive multifocal leukoencephalopathy. A new drug developed by Prat’s laboratory in cooperation with a pharmaceutical company is currently being tested as a potentially safer alternative.

Prat’s research shows how reverse engineering the complexity of the blood-brain barrier can point the way to promising clinical tools. Just as companies now hire former hackers to find the weak points in their network, scientists are looking for the cracks in the wall of the BBB, so that they can be either repaired to treat disease or exploited to deliver drugs to the brain. While nobody wants to revoke the brain’s privileged security system, it will be helpful to know the code.

by Tiffani Washington

Whether it’s from a movie, celebrity hearsay or some other largely fictional account, most of us can recall a tale of someone experiencing a heart attack in the throes of passion. In reality, only about 1 percent of all heart attacks occur during sex, and far less than 1 percent of heart attack survivors die due to a sexual encounter. Still, it’s easy to see why a recovering heart attack survivor might be a bit timid rekindling romance without a doctor’s green light.

Supporting that notion, a new study finds that patients who were sexually active before suffering a heart attack were one and a half times more likely to recapture their sex lives if they received guidance on the topic before leaving the hospital.

While it’s no surprise that sexual activity tends to decline slightly for both men and women during the year following a heart attack, or acute myocardial infarction (AMI), researchers found that many patients who said they did not get medical counsel prior to hospital discharge either unnecessarily delayed or refrained from sex.

In a survey of 1,879 heart attack patients, less than a half of men and roughly a third of women recall receiving instructions about when to safely return to sexual activity before leaving the hospital. After a year of follow-up, only 41 percent of men and 24 percent of women reported having a discussion with their doctor about sex since their heart attack.

Results from the study published  in The American Journal of Cardiology are in line with early findings presented at an American Heart Association conference in 2010. Lead author, Stacy Tessler Lindau, MD, associate professor of obstetrics and gynecology at the University of Chicago Medicine, said the study underscores the need for more doctors to address sex as an important part of overall physical function, even after a life-threatening event such as a heart attack.

“Doctors need to understand the significant role they play in helping AMI patients avoid needless fear and worry about the risk of relapse or even death with return to sexual activity,” said Lindau, a renowned expert on helping women with complex illnesses maintain sexual function. “Receiving instructions, prior to hospital discharge, about resuming sex was a major predictor of whether patients resumed sexual activity in the year following AMI. For women, this was the only significant predictor. The discharging cardiologist has detailed knowledge of the patient’s condition, has provided life-saving care and is best positioned to advise on the safety of engaging in physical activity, including sex.”

Without counseling, patients are left to make their own, often flawed, assumptions about risk associated with sexual activity. Multiple studies have shown that sex puts less of a strain on the heart than people might think.

“This study may help doctors address issues that they’re traditionally reluctant to discuss,” said study author, Harlan Krumholz, MD, professor of medicine and epidemiology and public health at Yale University School of Medicine. “We’re showing that addressing sexual health may make a difference to long-term outcomes.”

Current guidelines developed by groups of leading cardiologists, including Krumholz, state that stable heart patients without complications can resume sexual activity with their usual partner within one week to 10 days. In January, the American Heart Association (AHA) put more weight behind those recommendations with its most comprehensive review to date of research on sexual activity among heart patients. The report substantiated a longstanding rule of thumb: If patients can engage in moderate exercise - such as walking up a couple of flights of stairs - they are generally healthy enough for sex. The AHA also points to respected guidelines for care after AMI, which include patient counseling on resuming sexual activity.

“The goal is to restore a patent’s whole health,” said John Spertus, MD, of the University of Missouri in Kansas City, who designed the study. “That means not only minimizing further progression of coronary disease, but also maximizing quality of life.”

The researchers said doctors should resist making assumptions about which patients value their sexual lives. “The study shows that most male and nearly half of female heart attack patients are sexually active,” Lindau added, “and previous work has shown that even sexually inactive patients still view sexuality as relevant for health and overall quality of life.”

Lindau, Krumholz, Spertus and their colleagues are now honing in on the female patients in this study to understand how to improve their sexual outcomes after an AMI.

[For more on this research, see stories at: Daily Mail, Huffington Post and The Telegraph.]

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Lindau, S., Abramsohn, E., Gosch, K., Wroblewski, K., Spatz, E., Chan, P., Spertus, J., & Krumholz, H. (2012). Patterns and Loss of Sexual Activity in the Year Following Hospitalization for Acute Myocardial Infarction (a United States National Multisite Observational Study) The American Journal of Cardiology, 109 (10), 1439-1444 DOI: 10.1016/j.amjcard.2012.01.355

In 2006, Dale Lloyd II, a 19-year-old freshman football player at Rice University, collapsed during a conditioning workout and died the next day. His death was linked to complications from sickle cell trait, or having one of the genes that causes sickle cell disease.

At least 20 deaths of football players with sickle cell trait have been reported since 1974. As part of a settlement with Lloyd’s family in 2009, the National Collegiate Athletic Association (NCAA) agreed to screen all athletes for sickle cell trait. But does this policy make good medical sense, or does it discriminate against athletes with sickle cell trait and unnecessarily exclude them from sports? Lainie Friedman Ross, MD, PhD, the Carolyn and Matthew Bucksbaum Professor of Clinical Medical Ethics, recently surveyed pediatricians and sports medicine providers about the NCAA policy and found conflicting responses to these questions.

Sickle cell trait is most common among African Americans but can affect Caucasians as well, particularly those of Mediterranean and Middle Eastern origin. It can cause red blood cells to change shape and clog blood vessels, which can lead to heat illness, dehydration, kidney failure and exertional rhabdomyolysis, or breakdown of muscle tissue. Athletes and military trainees with sickle cell trait are especially at risk during intense conditioning at high altitudes or in extreme heat and humidity.

The idea behind the NCAA policy is that coaches would be able to take precautions during practices and games for athletes with sickle cell trait, but Ross said anybody is at risk for heat illness under those conditions.

“People who have sickle cell are at increased risk, but anybody can die from heat exhaustion,” she said. “This isn’t just unique to sickle cell trait. The whole point is we should be protecting all of our athletes and military personnel.”

The United States military has long studied this issue, and found that modifying training on hot, humid days for all recruits — not just those with sickle cell trait — eliminated the excess risk of death from heat illness and exertional rhabdomyolysis for those with sickle cell trait. Under normal conditions, athletes with sickle cell trait can participate with no restrictions, so by singling them out instead of enforcing rules on practice conditions for all athletes, the NCAA may be discriminating against them.

“Even if sickle cell trait doesn’t affect their performance, it affects how they get measured for their performance,” Ross said. “If we’re going to discriminate against these kids in practice, we’re going to discriminate against them in games too.”

In two separate surveys published in Pediatrics and the Clinical Journal of Sports Medicine, Ross and her colleagues asked pediatricians and sports medicine providers about the NCAA policy.  More than 70 percent of both groups supported targeted screening for African American athletes in all NCAA divisions. At the same time, a majority of both groups also expressed concerns about discrimination against athletes with sickle cell trait. These answers seem to contradict each other. If providers were concerned about discrimination they wouldn’t support targeted screening versus screening all athletes, or they wouldn’t support the screening policy at all.

Although initially the NCAA recommended screening all athletes, when the policy was implemented in 2010, the NCAA required screening for only Division I athletes. The final policy also allowed athletes to opt-out of screening. Both pediatricians and sports medicine providers overwhelmingly supported the opt-out policy  (75 percent of pediatricians and 88 percent of sports medicine providers), which would also seem to contradict their support for screening in the first place.

Besides the potential for unfair treatment of athletes with sickle cell trait, Ross also has concerns with the NCAA’s testing method. The official policy recommends a test called “Sickledex” which tests only for the specific sickle cell hemoglobin. However, there are a number of variants of sickle cell disease that the Sickledex test doesn’t detect.  While these variants may not pose the risk of exertional heat illness, they do have implications for having a child with a sickle cell disease variant.  By using the Sickledex, athletes who test negative may misunderstand their risks in the reproductive context.

“You’re taking 18- to 25-year-old athletes and you’re telling them that they’re sickle negative,” Ross said. “So later they decide to get married and have a family, and they tell their partner they’re sickle negative, not knowing that they were using a really bad test.”

There is a more sophisticated test available that detects all the sickle cell variants, but it costs more than $100 to administer, versus $10 for the Sickledex test. Ross believes this is the main reason driving the NCAA’s recommendation. “It’s very problematic to use a really bad test,” she said. “If we’re going to do a test, let’s do the right test so we give kids the proper information about their sickle cell status.”

There has been a broader push to screen athletes for other health conditions as well. In Italy, for instance, athletes are screened for heart conditions during routine wellness exams. Ross said that while such screening policies are created with the best intentions, they risk excluding thousands of kids from playing sports who could otherwise participate with no health issues.

“We have 10 million kids playing sports in the U.S. each year. The Italian data found that nine percent of the children required further diagnostic work-up, and two percent were disqualified from sports participation.  That would be a huge number in the United States, she said. “It’s estimated that it would cost around $2 billion for this type of screening here, which translates into $330,000 to detect a single athlete at risk for sudden cardiac death and $3.5 million to prevent one death.”

The difficult part is putting those numbers into perspective, but Ross said we need to think hard about how and why we screen athletes. “Any death in a young, healthy person is a total tragedy. I’m not trying to minimize it,” Ross said. “But I also have to think on the flipside. From a medical perspective it’s not wrong to screen people, but it’s the unintended consequences of the policy that are the problem.”

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Koopmans, J., Cox, L., Benjamin, H., Clayton, E., & Ross, L. (2011). Sickle Cell Trait Screening in Athletes: Pediatricians’ Attitudes and Concerns PEDIATRICS DOI: 10.1542/peds.2011-0187

Acharya, K., Benjamin, H., Clayton, E., & Ross, L. (2011). Attitudes and Beliefs of Sports Medicine Providers to Sickle Cell Trait Screening of Student Athletes Clinical Journal of Sport Medicine, 21 (6), 480-485 DOI: 10.1097/JSM.0b013e31822e8634

by Rob Mitchum

A common feature of pharmacies and organic grocery stores is the aisle of natural remedies, featuring bottle upon bottle of herbs, extracts, and oils that promise a wide range of medical benefits. For legal reasons, the health claims made by these products are often fuzzy, boasting of vague antioxidant or anti-inflammatory activity. But online, the compounds are touted as a cure-all for everything from the common cold to depression to cancer, despite often scarce scientific evidence to support such claims. In many cases, scientists aren’t even sure what these compounds do on a biological level, limiting their usefulness in the clinic even if an anti-disease effect could be conclusively demonstrated.

The major obstacle to determining how a natural remedy works (or doesn’t) is the difficulty in assessing the totality of its effects upon a cell, rather than just the effect on one particular factor at a time. But a technique recently invented by University of Chicago researchers to monitor the activity of hundreds of proteins at once allowed scientists to assess the anti-cancer potential of one natural remedy aisle staple: beehive propolis.

“A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy,” said Richard Jones, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology. “Now we’ll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds.”

Beehive propolis is a sticky resin that honeybees use to patch up holes and fill cracks in their hives. Natural remedy suppliers sell this “bee glue” in the form of capsules or liquid extract, touting its abilities to boost immunity, fight off infections, and soften skin. According to anecdotal reports, the substance has been used for centuries to treat sore throats, allergies, and burns, or for less medicinal purposes such as car wax and instrument polish.

Chih-Pin Chuu, at the time a post-doctoral researcher in Jones’ laboratory, wanted to examine whether the active compound in beehive propolis — called caffeic acid phenethyl ester, or CAPE — was effective against cancer cells. Testing concentrations of CAPE that you would expect to find in the blood after a person swallowed a propolis capsule, Chuu found the compound successfully inhibited the growth of early-stage prostate cancer cell in culture dish experiments. Subsequent experiments on mice implanted with human prostate cancer cells confirmed CAPE’s anti-cancer effect, and hinted at a mechanism.

“If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace,” Jones said of the results, published in the journal Cancer Prevention Research. “So it doesn’t kill the cancer, but it basically will indefinitely stop prostate cancer proliferation.”

That activity suggests CAPE could be a promising co-treatment alongside a chemotherapy drug that targets the cells. But if CAPE were to truly make the crossover from holistic remedy to clinical option, the scientists would also have to demonstrate how the compound freezes cancer cells in a non-proliferative state. Enter the micro-western array, the innovative proteomics technique first described in 2010 by Jones and colleagues.

Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples. Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth — experiments that would have been prohibitively expensive without the new technique.

“What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that’s never been possible before,” Jones said. “It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies.”

With the micro-western array, researchers could quickly build a new model of CAPE’s cellular effects. Treatment with CAPE suppressed the activity of proteins in the p70S6 kinase and Akt pathways, both important sensors of sufficient nutrition that give the green light to cell proliferation when activated. To confirm that this suppression was the key mechanism for CAPE to stop cell proliferation, the team confirmed that over-expressing components of those pathways protected the cancer cells against the compound’s effects.

“It appears that CAPE basically stops the ability of prostate cancer cells to sense that there’s nutrition available,” Jones said. “They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition.”

Despite the promising results in laboratory and mouse models, much more testing would need to be done before CAPE could legitimately be considered a clinical weapon against prostate cancer. One concern is that there is nobody with deep pockets to pay for the clinical trials needed to prove its effectiveness and safety in humans, since CAPE/propolis is a widely available, over-the-counter compound that can’t be patented by a drug company seeking profit. But Jones hopes that settling the issue of what CAPE (or other natural remedies the lab is currently testing) does to cellular pathways could make clinicians more comfortable in trying them alongside traditional drugs.

“It’s a rare event that a drug that’s not put forth by a pharmaceutical company goes through a clinical trial, so we’ll see how that works,” Jones said. “But if we were able to work out the mechanisms, you could say, A-ha, this compound would actually be beneficial in combination with other commonly-used therapies.”

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Chuu, C., Lin, H., Ciaccio, M., Kokontis, J., Hause, R., Hiipakka, R., Liao, S., & Jones, R. (2012). Caffeic Acid Phenethyl Ester Suppresses the Proliferation of Human Prostate Cancer Cells through Inhibition of p70S6K and Akt Signaling Networks Cancer Prevention Research, 5 (5), 788-797 DOI: 10.1158/1940-6207.CAPR-12-0004-T

by Dianna Douglas

Forty years ago, discussing your plans to donate your organs if you were to become brain dead was considered extremely poor taste.  “People didn’t talk about death and demise in polite company,” said Allen Anderson, MD, associate professor of medicine. He’s director of the advanced heart failure program at the University of Chicago Medicine, and has seen public attitudes about organ donation gradually shift away from macabre fascination and horror in the 1970s, when the concept of brain death was still evolving. “Even after organ donation became more viable, people had a hard time talking about this,” he said.

Not anymore. As of yesterday, Facebook has added an “organ donation” status update page to every account in the U.S. and U.K. These organ donation conversations are public like never before.

Families were once likely to object to someone offering herself up as a donor. Many people feared that the hospital staff wouldn’t do enough to save a dying patient if they already had plans to harvest her organs, or that the surgery to remove the organs would inflict more pain on the patient. For a long time, becoming an organ donor upon death remained a private wish.

“Medicine has progressed and we’ve come to understand brain death. Now, organ donation is not so charged,” Anderson said. In fact, 90% of the public supports organ donation in theory. But when pressed, somewhere between 30-40% of people refuse to turn over the organs of a loved one.

“We always suggest that organ donors discuss their decision with family and loved ones,” said Michael Millis, MD, professor of surgery and section chief for transplant. These conversations serve two purposes: the family knows their wishes, and there is a domino effect when people see others doing something that they once found creepy, or something that they had never considered.

“Organ donation saves lives and eases the suffering of thousands of families,” Millis said.  “Anything that increases awareness of organ donation is helpful.”

Currently, 57% of the people in northern Illinois and northwest Indiana are registered as an organ donor. “We have a good system for getting people to register,” said David Bosch, Gift of Hope communications director. “But we need 90% registered.”

Gift of Hope arranges organ allocation in northern Illinois and northwest Indiana. Bosch still combats persistent myths about organ donation, mostly through educational events in which organ donors and organ recipients share their experiences with the community.

“We’ve had positive media stories, and will sometimes see spikes in visits to our website and donor registrations,” Bosch said. He’s hoping that the Facebook bump will be more permanent. “Most of our outreach is asking each donor to tell two friends, and asking them to tell two more friends. The Facebook attention is powerful because the audience is a billion people.”

There are currently 790 patients on the waitlist for an organ transplant at the University of Chicago Medicine. Many will get organs this year, some will get better without a transplant, and a few of them will die waiting.

The organ shortage is so severe, Anderson says, that even if every person in the country who became brain dead in a hospital gave up their organs, it wouldn’t be enough. “If you commanded every suitable donor to be utilized for donation, we would still have a shortage,” Anderson said. For example, there have only been 1,100 donors in the United States this year. But 73,000 active candidates are waiting. An average of 18 of them die every day.

“There has been a leveling off of cadaveric donors,” Millis said. It’s a result of many factors, including improvements in medical treatments of stroke and brain injury, and the growing use of seatbelts and motorcycle helmets. Millis said that advances in transplant medicine have countered this decrease. “We have been able to expand the criteria of organs that we can accept for transplantation,” Millis said. Millis has found novel ways to transplant the liver of an older child into an infant, for example.

As more people live longer with organ transplants, they become walking advertisements for donation. “When people know someone who gets an organ, it changes the way they look at the process of organ transplant,” Anderson said. His patients, deathly ill when they went through transplant surgery, sometimes live for decades after receiving an organ. “Family members especially become tremendous advocates of becoming organ donors, because they see the benefit.”

Anderson said that almost everyone who encounters a recipient of organ transplant is changed by it. “People sign up when they know someone whose life was saved.”

If the conversation about future organ donation does indeed move to Facebook, it could change the conversation that happens at the bedside of someone who has become brain dead.

“When someone dies, their body belongs to their next of kin. No one can just take your organs,” Anderson said. “All sorts of factors go into whether a family is willing to provide consent in that moment,” Anderson said. Whether a person expressed their wish to donate can influence a family.

To stop families from overruling a dead person’s wishes, Illinois now has a “first-person consent” registry for organ donation. It was established in January 2006 to allow people to make binding decisions about organ donation upon their death. “You don’t need any other consent to donate if you’re registered with the state,” Millis said. While posting an “organ donor” status update on Facebook is not binding with the state, a link sends people over to the Illinois registry if they click the status update on Facebook. “That has to stay in place for the Facebook initiative to make a lasting impact on donation,” Millis said.

The Facebook plan could make the approach easier when the time comes to talk about organ donation in a hospital. “Even a person who didn’t register with the state or put it on their driver’s license can sign up on Facebook,” said Ozzie Rivero, a manager of organ procurement for the University of Chicago Medicine. “It’s not legally binding, but it might help the family come to a decision.”

by Rob Mitchum and Matt Wood

When superstar Derrick Rose crumpled to the ground late in the Chicago Bulls game Saturday, the playoff hopes of Chicago basketball fans followed suit. Experienced sports fans saw the point guard grabbing at the front of his left knee and thought immediately of three dreaded letters: A, C, and L. Sure enough a subsequent MRI confirmed that Rose had torn his anterior cruciate ligament, an injury that would knock him out of this year’s NBA playoffs, the Olympics, and a significant chunk of the next season.

Despite the long rehabilitation time, an ACL tear is a common injury for athletes playing sports that involve frequent cutting and pivoting. J. Martin Leland, assistant professor of surgery at the University of Chicago Medicine, performs 75 to 100 ACL reconstructions each year on recreational athletes who injured themselves during basketball, soccer, lacrosse, or skiing activities. On Monday, after repairing the ACL of a cricket player, Leland sat down with ScienceLife to discuss how ACLs are torn, how they are repaired, and “the perfect storm” of factors that may have led to Rose’s injury.

Q: First of all, what is the ACL?

The ACL is one of four major ligaments in the knee that stabilize the knee. You have one ligament on the inside of the knee called the MCL or medial collateral ligament, one ligament on the outside of the knee called the LCL, or lateral collateral ligament, then two ligaments in the center of the knee: the ACL, which is right in front of the PCL, or posterior cruciate ligament.

The ACL is most important for rotational stability of the knee, so if someone has an ACL rupture, once the knee comes down and the swelling goes away, they’ll find they can walk, jog, go up stairs, no problem. Then, if they get an MRI showing an ACL tear they’re very confused: “How can I possibly have an ACL tear if I can walk without difficulty with no pain?” But the ACL is not important for walking, it’s important for rotational stability.

Q: What happens to a person’s knee right after they tear the ligament? Are they in pain?

The ACL has an artery that runs right up the center of it. So the first thing that happens is the knee typically swells up like a balloon in a matter of an hour to two hours. Normally people have difficulty putting weight on it because it just feels weird. Some people will describe a pop, other people won’t, but you’ll feel like a sharp shooting pain in the knee, and then it will be gone, and it won’t really hurt. But the knee typically tends to get very swollen within 1 to 2 hours usually, and will stay swollen for up to a week, so people tend to say they have trouble putting weight on it for anywhere between immediately after the injury and four or five days. After that they can put weight on it, but the knee is very stiff, and it takes anywhere between a week and three weeks for that swelling to go down and the stiffness to go away so that you can get range of motion again.

Q: With Rose’s injury, Bulls trainers were doing knee exams right on the court after he collapsed. Can a doctor diagnose an ACL injury that quickly?

The Lachman exam is the name of the test that’s typically done to test the ACL. It’s done with the knee at 30 degrees of flexion. Basically, you stabilize the femur, and with your hand on the tibia, you just kind of pull up. If you feel increased laxity, or the tibia pulls forward on the femur more than what’s normal, you know right off the bat that they tore their ACL.

When I watched the video, I could tell that he had ruptured his ACL without even examining him. The sportscasters couldn’t tell the instant when he injured it, they said he jumped up and was complaining of pain, so maybe it was the jump. But it was when he planted, immediately before jumping. If you watch the clip very carefully, you can see he comes in, plants, and his left knee bows in, so that the knee comes towards the right knee as well as rotates, and then he comes out of that and jumps up. That’s why he dishes the ball off, because the second the knee went in that position, he felt it pop, and felt the pain, and you can see for a split second the classic valgus instability where the one knee moves towards the other knee and ruptures the ACL.

Q: Was it unusual that Rose injured his knee without being struck by another player or running into an object?

The most common way of tearing your ACL is non contact. It was the perfect storm for Derrick Rose to rupture his ACL. He’s missed much of the season because of his prior four injuries, and he’s only been back playing for three weeks, and it was in the last minute and a half of the game. He can’t possibly be at full strength because he missed so much time, so his muscles are more weak.

He went to make that sudden stop, and normally, if he was a little bit stronger, his muscles would have fired and kept his knee still. But his muscles were fatigued and they just gave out, and once they gave out, his knee started going into that position. Basically, he was coming in and stopped with such force that normally his muscles would have kicked in and stabilized his leg, but because his muscles were weak, his knee just kept going, and then ruptured the ACL. So it was really the fact that he wasn’t at 100 percent strength, and the fact that he was fatigued at the end of a game.

When you hear about skiers rupturing the ACL, it’s almost always in the afternoon, because someone like myself who is a recreational skier is not used to 8 hours of sports participation because we work all day. In the afternoon, my muscles are tired and fatigued, and that’s when my knee gets in that bad position.

Q: Is the ACL the most fragile knee ligament, or do sports fans just hear about those injuries more often?

The most commonly injured ligament in the knee is the MCL. But the MCL when injured in isolation, it heals very well non-operatively. So some people will be in a knee brace for six weeks and then get right back out there. Professional football, if it’s a mild injury, they might not even miss a game. People are injuring their MCLs all the time but we never hear about them, because it’s not nine months until you come back, it’s anywhere between two and six weeks.

Q: Is basketball one of the worst sports for causing ACL injuries? Who’s at highest risk for the injury?

There are some studies that have been done, and it’s been shown that women who play soccer and basketball have a much higher likelihood of developing ACL ruptures, versus men or women who play other sports. It hasn’t been shown in men’s sports that basketball is any more dangerous than say football or soccer.

It’s sometimes shown that women have an even higher risk of rupturing their ACL than men. There’s a 2 to 4 times higher rupture risk in women that play soccer or basketball in comparison to male counterparts, because of different reasons. Hormones tend to stretch out ligaments and estrogen can cause increase rupture of ligaments when there’s stretching at certain times of the menstrual cycle. Women also have proportionally smaller ACLs, even accounting for the fact that women are slightly smaller than men. But there haven’t been any research to show that men who play basketball are at a higher likelihood of injury than men who, say, play soccer.

Q: When the ACL is torn, is the treatment always surgical?

Assuming the ACL is completely ruptured, generally speaking with a cutting and pivoting athlete, especially a high level athlete, the treatment is always surgical. In patients that have a partial ACL tear where the cell fibers have been stretched but not completely torn and it’s just a little bit loose, they can usually be treated with rehab and then getting them back to sports. But if the fibers are completely torn, you usually recommend reconstruction because you can’t repair the ACL. If you try to put stitches in the ACL, they’ll just pull right through. You’ve got to actually pull that torn tissue out and put other tissue in its place, either from the patient’s patellar tendon or from their hamstrings. Occasionally, people will use a quadriceps tendon or tissue from someone who died, which is called an allograft or cadaveric tissue.

The reason why we recommend surgery is because 90-plus percent of people who have an ACL tear will continue to have instability, and if they try to get back into sports without having reconstruction, it’ll pivot out of place again. Every time the knee pivots out of place, you risk doing damage to the cartilage or the meniscus, and sometimes you can actually do damage that can’t be repaired. If you allowed Rose to continue playing, he probably wouldn’t be able to play, because every time he’d pivot on his knee, his knee would buckle, it would swell up, and he’d be done for the game. Then it will buckle again as soon as he went back on the court, and he might do more permanent damage that can’t be repaired and could lead up to shortening his playing days.

Q: How serious is the surgical procedure?

It’s outpatient surgery, the patients come in and go home the same day. Sometimes they wear a brace post-operatively for anywhere between two and six weeks depending on the surgeon’s preference. Within six weeks they’re walking around doing fine, usually very good range of motion in the knee, but it’s still quite some time until that ACL can be healed in, and quite some time until they get their strength back.

Q: What is a reasonable amount of time to expect Rose to be sidelined?

With recreational athletes we tend to let people get back to sports at about six months, because it takes about six months for the graft to heal in and for them to get some of their strength back. However, professional athletes obviously have to be at a much higher level of function, and need to be much stronger than your recreational athlete. In order to get that recreational strength, usually professional athletes will say anywhere between 9 months and a year.

When I was working with the Philadelphia Eagles, Donovan McNabb tore his ACL and had it reconstructed. Nine months into his recovery he was telling reporters he was about 75 percent back, because he understood in order to get back on the field, he had to be literally 100 percent, the best shape he’d ever been in in his life, or else he would get crushed by someone on the defense. Recreational athletes tend to get back a little sooner because you don’t need that same level of strength. But for professional athletes it’s usually 9 to 12 months, which means not only will Derrick miss the entire playoffs, no matter how long they go for the Bulls, he’ll miss the Olympics, and probably miss anywhere between the beginning and the entire first half of this next season.

Q: Over those nine months, what is happening? Is it all rehabbing to get the strength back in the new ligament

For the first 2 to 4 weeks, you’re trying to decrease swelling, make the patient more comfortable, get the swelling out of the knee so the quads can function. When the knee has a big swelling in it, the quads actually shut down, they go to sleep. So you’re getting the swelling out of the knee, getting the range of motion back, and making the patients feel comfortable.

In months 1 through 3, post-operatively, you tend to slowly start working on a little bit of strengthening but not pushing things too hard because you’re still really allowing that ACL to be healing in. Months 4 through 6 you’re really starting to work on strengthening, you’re getting more confident that the ACL is either healed in or mostly healing in, and really starting to work on strength. And then months 6 to 9 to 12, you’re really working on getting that 100 percent strength back so you can get back on the field.

Q: What are the chances of re-injuring the knee after an ACL reconstruction? Will Derrick Rose ever be the same player again?

The treatment has changed a lot, it’s constantly changing. The way in which we do ACL reconstructions is very different, especially with where we put the ACL, from what we did even five years ago. However, it’s been a very successful surgery for quite some time. We frequently will tell patients that 90 to 95 percent of people will get back to complete activity with no problems from where they were pre-operatively. But what we’re finding now from the long-term literature is that with procedures from 10 to 20 years ago, maybe only 50 percent of people truly got back to that elite level of activity. But techniques are constantly changing, it’s been a very successful surgery for quite some time. I would even venture to say that when we look back 15 years from now, we’ll have even better results than what we had 10 years ago.

For Derrick Rose, who is only 23 years old, this is not going to be a career ending injury for him, he will get back.

Q: Are there any common myths you often hear from patients about ACL injuries or reconstruction?

One myth would be that not every person needs to have their ACL reconstructed. I would say that every athlete needs to have their ACL reconstructed; if you tore your ACL playing a sport, you probably need to have it reconstructed if you ever want to play that sport again. But if you have a 60-year-old patient who missed a couple stairs and ruptured their ACL, they could do very well non-operatively, just as long as they don’t play any cutting or pivoting sports, or any aggressive cutting or pivoting maneuvers. If you imagine the average 65-year-old patient, they’re not really doing very much cutting and pivoting, and they might do well without surgery.

by Rob Mitchum

Too often, art and science are treated as intellectual adversaries. Educational systems typically route students toward one pole or the other, with the artistic and scientific spheres rarely intersecting by the time one reaches the undergraduate and graduate levels. But for the last two years, the University of Chicago has paved a path between these two fields with the Arts|Science Initiative, which offers grants to collaborations that reach across the traditional boundary lines.

This year’s presentation, which took place in the “performance penthouse” of the brand-new Logan Center for the Arts on the south end of campus, featured six such partnerships formed between scientists and doctors-in-training on one side and artists, sculptors, and filmmakers on the other. The projects covered a wide span of ideas and technologies, from 3-D sculptures based on math theorems to hacked Wii controllers that allow dancers to make music as they move. In each case, the participants raved about how the collaboration allowed them to flex a different part of their mind, approaching familiar topics with a fresh set of eyes and think about new, creative ways to merge the artistic and the scientific.

Trauma Under the Microscope: Collected Perspectives on PTSD

Post-traumatic stress disorder has frequently been in the headlines lately, as tragedies such as the killing of 17 Afghan civilians by a US soldier draws attention to the high incidence of the condition in veterans of war. But the definitions of “trauma” and “PTSD” vary widely from person to person, clouding the issue of what causes the disorder and how it is diagnosed and treated. Many journalists and laypeople misuse the term, or fail to understand that PTSD is caused by a constellation of factors, not a single incident of trauma, said Nicole Baltrushes, a Pritzker School of Medicine student.

So Baltrushes collaborated with Sravana Reddy of the Computer Science program and Carmen Merport of the English Department to create an interactive website on PTSD. Starting with a print flyer, the team asked friends, family, faculty members from several disciplines and health professionals to annotate the flyer based on their understanding of the disorder and its terminology. They then took those notes, plus various multimedia links to poetry, videos, pictures, Facebook posts and other sources, and built an interactive webpage that can be added to and customized by users.

“The hope is that as more people visit the site, and as more people hear about the site, that there can be a web-based conversation that we start about what is trauma and PTSD, to broaden our understanding,” Baltrushes said. “Because as of yet, we have not the greatest understanding of what these things are, or how to even approach healing of these things on any level.”

Opening

As laboratory imaging technologies improve, science becomes more and more of a visual discipline. In the film “Opening,” Jared Clemens of the Committee on Neurobiology and Marco G. Ferrari of the Department of Visual Art make the connection between scientific videos and the world of film explicit through innovative use of split screens, montage, and audio editing. While original footage featuring neuron-esque trees on the University of Chicago campus runs in the middle of the screen, laboratory videos of actual neurons run on the left side while scenes captured from films such as Elephant Man, The Shining, and Rear Window play on the right. Meanwhile, the audio track alternates between scientific descriptions of the structure and function of the brain and movie dialogue that touches on the nature of the mind.

“This piece originated in a personal interest in the disconnect that exists between much of the public and the sciences,” Clemens said. “I wanted to explore this in a non-traditional way…the structure of the piece is an abstraction of the chaos and dynamics that exist in neural circuits, as well as the chaos that exists between the public and the sciences.”

To bring the work to the public, Clemens and Ferrari will project the eight-minute film starting at sunset on May 11th onto a very appropriate canvas: the Surgery Brain Research Institute entrance on the east side of the University of Chicago hospital complex.

El Shaddai

For the Fall 2009 issue of Medicine on the Midway, Pritzker medical student Philippe Tapon told the story of Manoj Rana, a 26-year-old man who suffered burns over 95 percent of his body in a house fire. Since then, Tapon has continued to expand Rana’s story into a book-length work, entwining his story with the experiences of a woman who experienced a different sort of trauma through years of sexual abuse. To add a visual element to the story, Tapon collaborated with Stacee Kalmanovsky and Clare Rosean of the Department of Visual Arts, who provided original art and photo collages.

As a demonstration of this multi-media approach, Tapon read an excerpt from his book alongside a slideshow including photographs of Rana’s injuries, Kalmanovsky and Rosean’s art, and medical illustrations. Before the reading, Tapon explained how writing about these cases and collaborating with people outside of the medical field helped him to reconcile his clinical perspective as a doctor-in-training with a more emotional view of a patient’s recovery from trauma.

“I was interested to explore what the medical gaze meant; that effort to come up with an objective, scientific, rational description of an event, and yet somehow be unmoved and not bring my own personal bias into this,” Tapon said. “[My advisor] Dan Brauner helped me to understand that this was in some sense a fiction created by doctors to help them with their work. Bringing in Stacee and Clare, who did not subscribe to this belief into the work, helped me a great deal.”

In a recent column in the New York Times, Nick Kristof pointed out a startling statistic: for every American soldier killed in combat this year, 25 will commit suicide. A report from the Center for a New American Security says that from 2005 to 2010, service members took their own lives at a rate of one every 36 hours, and the Department of Veterans Affairs says that 18 veterans commit suicide every day.

Further analysis of this epidemic uncovers even more troublesome data. In a recent study published in the American Journal of Public Health, a statistician from the University of Chicago Center for Health Statistics found that the youngest group of veterans, ages 17-24, were almost four times as likely to commit suicide than nonveterans.

Robert Gibbons, PhD, professor of biostatistics in the departments of Medicine and Health Studies has long been interested in statistical analysis of suicide data to uncover patterns that could point to potential intervention strategies and treatment policies. He was on the Food and Drug Administration (FDA) committee in 2004 that issued a “black box warning” about increased suicide risk in children taking antidepressants. He actually voted against the warning, citing concerns about ambiguous data, and earlier this year published his own statistical analysis of the clinical trials the FDA used for their warning and found that the drugs were quite effective in decreasing suicide risk in adults and neither increased nor decreased suicide risk in children and adolescents.

In his current work on veteran suicide, Gibbons and his colleagues tackled another statistical disagreement. The editors of the American Journal of Public Health asked him to write an editorial about two studies on the rate of suicide among veterans that showed conflicting results. He and his colleagues weren’t able to replicate the results of either study, so they decided to do their own using publicly available data.

“We realized there was just no way we were going to be able to be Solomon-like and opine about who was right or wrong,” Gibbons said. “So we decided to see if we could figure out a way to shed some light on the answer using stuff off the internet, something a 10-year-old could get.”

Those data are from the Centers for Disease Control and Prevention National Violent Death Reporting System, which provides detailed data on all violent deaths, including suicides, from 16 states from 2005 to 2008.

“It’s a very important data source that very few people know about or use, so we’re really happy to use it. It’s a great national resource,” Gibbons said. “I think what’s cool about it is that it shows you can actually learn something from data that are completely publicly available, and learn something that is probably right.”

The key difference in how Gibbons and his colleagues analyzed the data versus the two previous studies is that they looked at how the rate of suicide changed with age. Statistical analysis of epidemiological data commonly controls for age, but a more detailed stratification by age is required to tease out the effects of recent military service and the associated emotional and psychological traumas of war.

The problem with the two conflicting earlier reports was that they were based on national surveys that did not control for the time at which the veterans actively served in the military.  One study included veterans with more recent military service and identified an increased risk of suicide risk. The other study looked at veterans further removed from military service and did not find an effect.  Gibbons and his colleagues explained these differing conclusions in the editorial using their new results.

“The bottom line as it turns out there’s a really big risk of increased suicide right when you get out of your military service,” Gibbons said. The risk of suicide in the youngest group of veterans was almost four times higher than nonveterans. That number drops off after the age of 24, but remains around one and a half times higher.

The Department of Veterans Affairs recently announced that it will be hiring 1,600 additional psychiatrists, psychologists, social workers and clinicians to address veterans’ mental health needs, and there is evidence that vets with post-traumatic stress disorder could be suffering from the same kind of brain disease associated with sports concussions. Gibbons said he hopes studies like this will underscore the problem and add urgency to these efforts.

“I think it’s the kind of thing that will drive dollars to make sure that veterans get the kind of treatment that they need for what obviously is a very life-changing experience,” he said. “The National Institutes of Health and the Department of Defense have launched a huge initiative to study suicide and the psychological and biological basis of suicide in the military. That’s a good idea because clearly there’s something going on.”

He pointed to the big spike on the graph of veteran suicide rates in the paper (shown above) and said, “You don’t go from this to this by chance.”

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Gibbons, R., Brown, C., & Hur, K. (2012). Is the Rate of Suicide Among Veterans Elevated? American Journal of Public Health, 102 (S1) DOI: 10.2105/AJPH.2011.300491