In the physician’s office, the communication between doctor and patient can be just as important as any medical exam or test. To set a patient on a healthy path, a doctor must explain diseases and treatments in a manner that is accessible and relevant to each individual. The conversation must also be a two-way street, with the doctor listening to the patient instead of merely lecturing. In the increasingly technical and hurried world of medicine, more and more of that critical interaction is lost to 10-minute appointments and physician switching.

To counter that trend, an exciting new institute was announced at the Medical Center this morning. The Bucksbaum Institute for Clinical Excellence at the University of Chicago will be made possible by a $42 million pledge from The Matthew and Carolyn Bucksbaum Family Foundation. The institute, inspired by the relationship between the Bucksbaums and their long-time physician Mark Siegler, will focus on how to improve doctor-patient interaction and train the next generation of doctors how to be advisers, counselors, and navigators for their patients.

“These generous donors have pinpointed a fundamental aspect of medical practice that deserves greater attention,” said Kenneth S. Polonsky, MD, dean of the Division of the Biological Sciences and the Pritzker School of Medicine at the University of Chicago. “They are giving us the resources to concentrate on training physicians who not only possess extraordinary technical knowledge but can work effectively with patients to reach the best clinical decisions.”

An announcement ceremony this morning will be followed by a panel discussion of the patient-doctor relationship and patient outcomes, with Siegler, dean of medical education Holly Humphrey, and Pritzker medical student Rebecca Levine participating. That event will be webcast live, and coverage will follow here on the blog this afternoon. In the meantime, you can read more about the institute at the New York Times, hear a story about it at WBEZ, and watch the official announcement video below.

Loneliness can be deadly. In humans, there is a statistical relationship between social interaction and mortality - the more isolated you are, the lower your chances of living a long life. Rats kept in social isolation their entire life die at a younger age than littermates who lived in groups closer to their natural social structure. But how exactly does isolation kill a rat? Under normal conditions, an infectious disease such as pneumonia is typically the cause of earlier mortality in a lonely rat. But when rats are kept in the sterile conditions of a laboratory animal facility, the cause of death is something quite surprising: breast cancer.

Those experiments - conducted by the group of Martha McClintock, professor of psychology at the University of Chicago - sparked a fruitful collaboration between McClintock and Suzanne Conzen, professor of medicine and a cancer expert. Last week, McClintock and Conzen gave a tag-team talk at the Chicago Breast Cancer SPORE seminar to present an overview of their research into the connection between social isolation, stress, and breast cancer, a line of study that could flip the current thinking about the disease. Traditionally, the psychological and social effects of breast cancer are considered to be the consequence of its diagnosis and treatment, but the research of these two laboratories suggests that these factors could be a cause as well, just as much as genetics or other biological sources.

“What I brought to the classic traditional approach is trying to flip it on its head,” McClintock said, “where you recognize that there are truly social forces which then change the psychological states of individuals in those interactions, and in turn their hormone function, cell receptors for those hormones, and then ultimately changes in gene expression.”

The link between the two labs was made over a hormone known for its role in stress responses, cortisol. McClintock observed that solitary rats behaved more anxiously than their group-housed peers, and found that they exhibit a larger and prolonged cortisol increase after a stressful event. Conzen’s laboratory was already studying the role of a receptor for cortisol, the glucocorticoid receptor (GR), in breast cancer, because women with the harder-to-treat “triple negative” form of the disease often show increased GR levels. Researchers in Conzen’s laboratory discovered that activating GRs can stimulate proliferation of breast cells and block the effects of chemotherapy drugs.

Could this be the missing biological step between isolation stress and breast cancer? At the lecture, Conzen tagged back to McClintock to talk about experiments on the tumors from her socially isolated rats. Unlike more common animal models of breast cancer where the tumor is instigated by a toxin or a genetic mutation, the naturally-occurring tumors in isolated rats show a similar diversity to that seen in human tumors. Some rats grow benign tumors, some malignant, and different tumors have the different hormone receptor profiles that are used for classification and treatment choices in patients - including, in some cases, glucocorticoid receptors.

“This to me was very exciting because in the rat model we have a good model of the diversity of breast pathology that happens [in humans] and it is increased by isolation,” McClintock said. “I was happy to see it in the more natural, spontaneously-occurring cancer model rather than something that was induced.”

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Students might sometimes think that their textbook appeared out of thin air, the accumulated knowledge of a field spontaneously forming into a heavy slab of facts and figures. But textbooks are like any other type of book, with flesh-and-blood authors who labor over the words within and make a million tiny decisions to shape the final product. If you try to include everything, the book will likely be too heavy for even the most determined or muscular students to carry. Cut too much out, and your definitive textbook might be scorned as incomplete and elementary.

In writing her new textbook, professor of neurobiology Peggy Mason helped find the happy middle by starting with a very specific audience in mind: the medical students that she has spent 15 years teaching at the Pritzker School of Medicine. Her completed product, simply named “Medical Neurobiology,” is the first designed with aspiring physicians in mind, teaching med students about the broad influence of the central nervous system. Picking a specific target audience helped Mason make the hard choices about what to include and what to leave out, she said - even if the final 660 pages is heavier than she intended.

“I think it’s actually the only textbook completely aimed at the medical students,” Mason said. “I did a few things because of that that no other textbook does.”

For starters, Mason chose not to interpret “medical neurobiology” as simply “neurology.” Only a small percentage of medical students will eventually choose to train as neurologists, but the other 97 percent also need to be familiar with the central nervous system, she said. Knowing the anatomy and function of the brain, spinal cord, and nerve pathways can help everyone from future neonatologists measuring infants’ reflexes to future pulmonologists treating asthma to future geriatricians looking for the warning signs of dementia or motor deficits.

Another important decision came to Mason after a dinner with four medical students who gave her insight into the overwhelming workload of an aspiring doctor.

“All of a sudden I just realized that the immensity of the knowledge base that they need to acquire in two years,” Mason said. “It made me think anew about what we were teaching them, and I decided that as entertaining as it may be for us to talk about the newest, greatest research, it’s a disservice to them. They don’t have the time; they need the body of information that they need clinically and not the extraneous stuff. So I tried to cut out as much as I could.”

Mason kept the page count down by restricting the coverage wherever possible to topics of clinical relevance, leaving out popular neuroscience textbook subjects such as the fundamentals of smell and leech swimming (a common model for the neurobiology of locomotion). Instead, she focused on the anatomical regions where patients are most likely to suffer lesions that cause symptoms, and the neurotransmitter imbalances that cause behavioral changes. Pop-out boxes describe the clinical manifestations physicians are likely to see, such as the pupil constriction and droopy eyelid of Horner syndrome, which indicates damage to a specific pathway from the brain to the eye.

But to really help important neurobiology topics take up permanent residence in the minds of medical students, Mason deployed an armory of inventive examples and metaphors to make the text both enjoyable to read and memorable.

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The future of genetic medicine comes in many flavors, from the discovery of the rare mutations responsible for uncommon diseases to the cataloging of variants that may be responsible for common diseases such as high blood pressure and diabetes. A segment from last night’s ABC 7 Chicago news focused on both aspects of this potential, jumping from a young man in Utah with Miller Syndrome to the 1200 Patient Project of the Medical Center’s Mark Ratain and Peter O’Donnell. Results from the project, currently underway, could help physicians customize medical treatments for individual patients, maximizing effectiveness while reducing side effects. As the segment says, if we really are heading toward a future where every patient has their genetic code read as routinely as they receive a doctor’s check-up, such research will be essential for unleashing the power of genetic medicine.

When the media hypes the healthy effects of drinking red wine in moderation, they’re talking about resveratrol, the chemical responsible for wine’s benefits. Scientists have long tested whether isolating that chemical can turn it into a super-pill for good health and long life without the alcoholic “side effects” of its normal route, with mixed results. But a new study featured in the New York Times this morning finds an intriguing benefit of a resveratrol derivative called SRT-1720. Obese mice given the experimental drug lived 30 percent longer - as long as control mice - rather than expiring earlier from obesity-related diseases such as fatty liver and diabetes. As the article states, such a drug may represent “more a moral hazard than an incentive to good health,” seen by some as a way of avoiding the consequences of excess. But with trials of the drug in humans still in their earlier stages, the ethical discussions will have to wait on the science.

Since our piece remembering famed bio-statistician Paul Meier ran last week, two more fine obituaries of the UChicago professor emeritus have appeared. Read the Chicago Tribune take to learn what instrument Meier learned to play at the Old Town School of Folk Music, and the New York Times version for the context of how Meier changed randomization in clinical trials forever.

Living shoulder to shoulder (or even closer, on the subway) in an urban environment feels like a particularly modern phenomenon. But as friend of the blog Tim de Chant explains in his guest blog at Scientific American, human societies have concentrated themselves since even the prehistoric hunter-gatherer days. For more of Tim’s great writing on the science of population density, visit his Per Square Mile blog.

Stress can have all sorts of negative effects on your health, but what about the stress of your spouse or partner? Not Exactly Rocket Science looks at a study in finches that suggests a high-strung life mate could actually shorten your life.

Muslims are the fastest-growing religious minority in the United States, with over 7 million Americans declaring themselves as followers of Islam and more than 2,000 mosques nationwide. But in spite of the numbers, little data has been collected about American Muslims’ beliefs about health and disease, or their experience in the U.S. health care system. One reason for this also lies within the demographics, as American Muslims are a particularly diverse minority, containing South Asians, Arabs, and African-Americans, as well as both recent immigrants and long-term, multiple-generation natives. With such a wide variety of members from different ethnic, racial, and socioeconomic backgrounds, how does one pin down the health care experience of American Muslims?

The only way, thought Aasim Padela, was to talk to all of them - or at least representatives from each of the major groups in the American Muslim community. For his recent report, “Meeting the Healthcare Needs of American Muslims,” Padela and his colleagues at the Institute for Social Policy & Understanding went to the rich Muslim community of southeastern Michigan, one of the largest Muslim populations in the United States. Reaching out to multiple mosques and holding focus groups with over a hundred participants, the group looked for common denominators of people who share the Islamic faith, but perhaps little else.

“We looked at American Muslims as a conglomerate and asked what was common,” said Padela, assistant professor of medicine and director of the Initiative on Islam and Medicine at the University of Chicago. “We wanted to talk to each of these three large groups, which we know comprise the majority of American Muslims, and look at what’s similar in terms of health care challenges and beliefs. What we found as similar is something we can attribute to their faith.”

The final product was a fascinating piece of medical anthropology, a snapshot of how American Muslims view their own health or illness, the struggles they face in the U.S. health care system, and their solutions for establishing stronger communication between their faith and their medical caretakers. In an environment where physicians are expected to meet their patients halfway on ways to prevent and cure disease, understanding the perspective of a community that is already large, and growing larger, is an important first step toward improved care.

One primary finding of the report describes the “medical narrative” of American Muslims, their views on where disease comes from and the most effective strategy for fighting it off. Many participants in Padela’s focus groups believed that God takes an active role in health and illness, perceiving conditions from a winter flu to breast cancer as divinely ordained.

“Most participants perceived illness through a religious lens as predestined,” the authors wrote, “a trial from God by which one’s sins are removed, an opportunity for spiritual reward, a reminder to improve one’s health, and sometimes a sign of personal failure to follow Islam’s tenets.”

One might think that treating such a patient would be difficult for a physician, faced with a patient that believes they are being religiously challenged through their illness. But Padela said that a closer understanding of Islam refutes these fatalistic notions, and that most Muslims agree that health issues are best confronted with a combination of spiritual and medical healing.

“God also says to take care of your body, and that means you have to go to people in this world,” said Padela, who conducted the research as a Robert Wood Johnson Foundation Clinical Scholar at the University of Michigan. “Doctors are a part of that, but only a part. Imams play a big role in healing, in the sense that they help you understand disease and illness.”

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Medical school isn’t cheap. Today, medical students graduate with an average debt over $155,000, and the need to pay off those mortgage-sized loans drives many a young doctor away from more modestly compensated but sorely needed fields such as primary care and family medicine. To alleviate this financial pressure, many organizations have started scholarships to help with the med school tuition bill, rewarding scholastic achievements and commitments to work in underserved populations. The American Medical Association’s Physicians of Tomorrow program is one such effort, and this week’s announcement of the 2011 recipients [pdf] carried a heavy Pritzker School of Medicine presence.

Two of the 18 (11 percent, but who’s counting) fourth-year medical students receiving the $10,000 scholarship were from the University of Chicago’s medical school. Laura Blinkhorn (left) and Maggie Moore (right) are the two very impressive Pritzker students among the recipients, each with very impressive biographies already built in their young careers. Blinkhorn has done work with South Side neighborhoods as part of the Pritzker Summer Service Partnership, works with the Washington Park Free Children’s Clinic, and is planning to spend 3 months of the next year doing a clinical rotation in the African country of Gabon. Moore volunteered at the Maria Shelter Clinic for Women and Children and the South Side “Girls on the Run” program, and somehow finds time to write poetry about her medical experiences. Because of poems such as “Cadaver Memorial” and a collection called “A Third Year’s Life in Lyrics,” Moore was given the Johnson F. Hammond, MD Scholarships supporting medical journalism by the AMA. Congrats!

New Furniture for Molecular Engineering

When you are building a new house, you’re gonna need some furniture. The same thing goes for building a new research institute - before you can fill it with people, you need somewhere for them to sit. The University of Chicago’s Institute for Molecular Engineering, which was born in December and acquired a leader in March, has this week announced four named professorships made possible by anonymous donations. The funded positions give the institute the power to recruit prominent researchers to help realize the institute’s unique vision blending biology, chemistry, and physics.

“The big job in front of us is to bring together people with expertise in broadly applicable areas of enabling technology, such as synthesis of new materials, biological engineering, new ways of doing computing and quantum information science,” said Matthew Tirrell, the founding Pritzker Director of the Institute for Molecular Engineering and senior scientist at Argonne.

Elsewhere…

The San Diego Union-Tribune Keith Darcé wrote an excellent overview of the Earth Microbiome Project, the global study of the world’s bacterial populations that has previously been featured on the blog. Our own Jack Gilbert is featured (he mentions their current project swabbing bacteria from the animals of the San Diego Zoo), and an interesting hunt for bacteria able to survive in high-salt conditions is also explained.

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Last November, a barrier was broken in the prolific Bollywood film industry of India. A film called Dunno Y featured the first on-screen male-male kiss - a provocative scene in a country that only the year before repealed a law making homosexuality illegal. Many tagged the film as India’s version of Brokeback Mountain, a controversial and progressive step in depicting male-male romance in popular culture that reflected a growing social acceptance of homosexuality. But the full significance of those cultural changes in the South Asian country have yet to be studied, and will require perspectives from law, anthropology, medicine, and more.

Just such a discussion will take place this Saturday morning at the University of Chicago and on the internet in the roundtable event, “Sexual Identity, Health and Stigma in India: Traditional Statuses and Western Influences.” Organized by John Schneider, assistant professor of medicine and epidemiology at the University of Chicago Medical Center and director of Global Health Programs, the discussion will be available worldwide on a webcast broadcast by the UChicago Facebook page, the Global Health Initiative website, and here on ScienceLife (watch this space).

“What I tried to do is bring together scholars from a number of different disciplines to make this a truly interdisciplinary discussion,” Schneider said. “I want it to be like a Sunday morning news program - but smarter - where a topic area is chosen and everybody fires away with their background about it, leaving room for remote viewer input.”

The central topic of whether sexual identity in India is truly shifting can be addressed from any number of angles. There’s the legal status of homosexuality after the 2009 repeal of Section 377 of the Indian Penal Code by the High Court of Mumbai. Or the sexual and mental health consequences after centuries of stigmatization of men having sex with men, including the spread of HIV and other sexually transmitted diseases. Or the pop culture ripples, such as Dunno Y, that may reflect changing attitudes and sexual roles in Indian culture. All of which are set against the backdrop of a country rapidly modernizing and playing an increasingly powerful role in global economy and society.

“I think that India is going through tremendous social and cultural changes as it emerges from what would be, in old terms, a less-developed economy to now becoming something of an economic powerhouse,” said Niranjan Karnik, assistant professor of psychiatry and behavioral neuroscience and another participant in the event. “This has the potential to really change the dynamics of the society and change the way people see themselves and behaviors.”

The participants in the roundtable are all accomplished researchers and experts on India. The keynote speaker, Lawrence Cohen of the University of California, Berkeley, studies medical anthropology in the country, and has written on homosexuality, aging, and organ transplant markets. Philip Kumar and Sanjay Srivastava are researchers based in India studying sexuality and advising the government on health issues related to men who have sex with men. Schneider himself has an extensive project underway in Indian truck drivers, where he is using cell phones in building a network of men who have sex with men to study their behavior and identify potential peer outreach points.

“One of the issues we are looking at is what changes in sex position roles might be occurring over time in India,” Schneider said. “Is a Western identity rubbing off on India, or is it developing a new identity? My work will help address those questions because of the cell phone network data that triangulates often sensitive self-reported data,” Schneider said.

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By John Easton

Let’s start with a statistic: almost 2,000 citations a year. One paper by Paul Meier, the Ralph and Mary Otis Isham Distinguished Service Professor emeritus of statistics, pharmacological and physiological sciences, medicine, and the college, has been cited more often, by a wide margin, than any other paper in the field. At last count it was the fifth most cited research paper of all time, in any field. With about 34,000 citations to date, Kaplan, E. L., and Meier, P. (1958), “Nonparametric Estimation from Incomplete Observations,” has been cited by another scientific publication about once, on average, for every day of Meier’s long life—he was born in 1924—and still counting.

Sadly, however, that ratio can only increase. Citation counting will continue, but the numbering of days stopped on Sunday, August 7th, when Professor Meier, a world-class statistician who made “extraordinary contributions to statistics and to society,” according to Columbia University - and everyone else - passed away peacefully at his Manhattan home.

The Kaplan-Meier estimator is used ubiquitously in medical studies to estimate and depict the fraction of patients living for a certain amount of time after treatment. This is not as simple as it sounds. Survival curves are complicated by the uncooperative way in which research subjects often behave. Some leave a study part of the way through. Others elect not to die before the study ends. These are known as “censored observations.” The Kaplan-Meier estimate is a simple way to compute the survival curve despite such troublesome behavior.

There was almost a Kaplan estimator and a Meier estimator. Each had submitted a separate manuscript to the Journal of the American Statistical Association, but the editor recommended that their papers be combined into one. It took them four years. “At one place he solved a problem that I couldn’t solve,” Meier later recalled in an interview [pdf]. “Other places I solved problems he couldn’t.” Finally published in 1958, it was only cited 25 times over the next ten years. Then, boosted by statisticians’ increased computing power, it caught on. It has since been applied to data from clinical trials of therapies for every disease from cancer to cardiology to concussion.

Friends and colleagues point out that this was only one of Meier’s fundamental contributions. He published many more studies, was a persistent and outspoken advocate for randomization in clinical studies, helped design some of the 20th Century’s most important clinical trials and trained many of the leaders in the field.

“Paul was a friend and colleague as well as one of the most influential statisticians of an important era,” recalled Stephen Stigler, the current chair of statistics at the University of Chicago. “He left an indelible mark on us, and through his research on the world’s clinic analytical practice. He will be missed and cannot be replaced.”

“I have been so fortunate and privileged to know this truly great, wonderful, helpful, kind man who was always so generous with his skills and wise advice,” said toxoplasmosis expert Rima McLeod, professor of ophthalmology and visual sciences at the University. “He is one of the founding fathers and giants of statistics in the past century. He was at the same time simply a modest, helpful, supportive and warm colleague who only let you know how special he was by the quality and content of what he said and wrote.”

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Being a parent these days is anxious business, with an onslaught of news reports telling you what might be good or bad for your child’s health and development. In many cases, these claims are based on scientific evidence that is preliminary at best, studied only in small subject pools or retrospectively. To comprehensively confirm a link between, say, breast-feeding and body weight or living near a smokestack and asthma, a large epidemiological study that tracks thousands of children from before birth to adulthood is necessary. But that kind of study is very expensive, thanks to costs associated with recruitment, data collection, and analysis over decades of time.

As such, it’s better to do one enormous study of many factors that potentially influence child health rather than several independent and costly experiments. Enter the $5 billion National Children’s Study, a federally-funded project that hopes to track over 100,000 American children from their mother’s womb to age 21 in order to test possible influences - genetic and environmental, positive and negative - to their health. Already 11 years in the making, the study is just completing its warm-up phase, hoping to start the main event in April 2012. But as Daniel Johnson and Angela DeBello presented at the University of Chicago Medical Center Pediatric Grand Rounds earlier this month, the study is already teaching researchers valuable lessons.

“We have a very ambitious agenda,” said Johnson, an associate professor of pediatrics at the Medical Center involved in the Chicago branch of the study. “We’re kind of learning how to do this as we’re going along.”

The Children’s Health Study was authorized as part of the Children’s Health Act of 2000, alongside improvements to child mental health care, anti-violence programs, and day care provider training. While many of the other initiatives have long been implemented, the CHS has taken more time to reach the launchpad due to the mind-boggling logistics involved. In order to break down the roughly 4 million U.S. births each year into a manageable study cohort, the project will collect medical and survey data on growing kids from 105 different counties reflecting almost every region of the country.

It’s a beautiful plan on paper, but executing the recruitment and retention of 100,000 children around the country is immensely difficult. Debello, the vice president and associate director of public health research at the National Opinion Research Center (one of the organizations charged with administering the CHS), said that pilot studies have revealed just how difficult it is to even find pregnant mothers eligible for the study. Researchers have tried surveying homes for women expecting children or trying to have children, working with medical providers who can direct eligible women to the study, and mailed surveys to try and find the right subjects. But the up-to-date numbers presented at grand rounds indicated the low hit rate of this full court press: of 28,000 households originally contacted in Cook County, only 67 women were found to be eligible for the study (and only 49 provided consent to participate).

“It’s pretty overwhelming…the numbers are going to get big very quickly as this study progresses,” DeBello said. “Not surprisingly, it was far more expensive than we expected it to be.”

Hence that large price tag, which Johnson admitted is high, while also suggesting that it could be a bargain in the end. Any costs spent on conducting the study should be weighed against the potential health care costs saved with the information it collects. There’s a lot of room to work with in child health costs, he pointed out - a study in the journal Health Affairs calculated that environmentally-mediated diseases caused by lead exposure, air pollution, and other toxins produced $76 billion in medical costs in 2008 alone. Johnson also pointed out that the results of a similarly large project, the Framingham Heart Study, has prevented an estimated 800,000 deaths despite only being 1/20th the size of the CHS.

“It’s still not clear how successful this study will be,” Johnson said. “But we think that the goals and aspirations are certainly strong reasons to drive us forward.”

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A large portion of medical research is dedicated to designing and testing new and better drugs for treating disease. But what if we could improve treatments with the drugs we already have - and potentially cut costs at the same time? That’s the proposal made in an editorial this week in the Journal of the American Medical Association written by the Medical Center’s M. Eileen Dolan and Vanderbilt University’s Russell Wilke. Their article, “Genetics and Variable Drug Response,” is an optimistic snapshot of the current state of pharmacogenetics, the use of genetic information to improve the use of pharmaceuticals.

Though individualized or personalized medicine has been a goal of physicians and researchers for several years, the science (as it tends to do) is moving slowly. But as Dolan and Wilke write, promising pharmacogenetics examples are beginning to accumulate, from genes for enzymes found to influence the metabolism of chemotherapy and anti-clotting drugs to genetic variants that predict severe side effects from various agents. Some of these discoveries have already made it to the clinic, such as the genetic test (developed at the University of Chicago by Mark Ratain) for a variant that affects the response to the cancer drug irinotecan. Physicians can use the test to lower the dose in patients found to carry the variant associated with severe side effects at the normal dose.

Dolan and Wilke dream even bigger about pharmacogenetics. Currently, the standard drug dose is set by the average response of a large population, hoping to capture a level where people get the most benefit at the least risk. But as more information about the genetics of drug response are revealed, those doses can be better shaped to each patient according to their own personal risk-benefit. This could bring some drugs deemed “too dangerous” back to common use, if some patients have a genetic profile that enables them to endure the treatment safely.

“For drugs with a narrow therapeutic index, pharmacogenetic studies may hold the potential to resurrect treatments previously withdrawn from the market, particularly for agents designed to fill underserved clinical niches,” they write.

If smarter dosing can truly bring effectiveness up and toxicity down, it would be a benefit to both patients and the health care system in general. One suggestion by the authors is to start building gene-based drug dosing into electronic medical records, creating alerts for doctors about “drug-gene interactions” similar to current alarms for potentially dangerous drug-drug interactions. The future of medication may be more complicated than “take two of these,” but smart implementation may save dollars and lives.

Cohen Video

The American Society of Clinical Oncology recently filmed a short video with Medical Center associate professor of medicine Ezra Cohen, where he talks about how he decided to treat cancer patients while working as a small-town family physician. It’s a nice piece about how doctors are inspired to do their work and the connection between laboratory research and clinical care. If you want to see more videos with Dr. Cohen, he discussed head-and-neck cancer with ScienceLife almost exactly one year ago.

Elsewhere…

Right after his very cool study on the genetic origins of limb development was published, evolutionary biologist Neil Shubin departed for his annual expedition to the Canadian Arctic in search of fossils from the earliest limbed creatures. If you want to follow along with the hunt, Shubin’s teammate (and Tiktaalik co-discoverer) Ted Daeschler is blogging from the dig for the Philadelphia Inquirer! Read about how their remote site on Devon Island is “almost like Mars,” and how the expedition is already finding interesting fossils two days into the trip.

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By John Easton

Salt is bad for you. According to a 2010 article in the New England Journal of Medicine, lowering dietary salt intake by 3 grams per day could “reduce the annual number of deaths from any cause by 44,000 to 92,000.”

Or maybe not. A 2011 meta-analysis of seven clinical studies of salt reduction, published this week in the American Journal of Hypertension, found “no strong evidence that salt reduction reduced all-cause mortality.” One of the seven studies showed that a low-sodium diet was associated with an increase in the risk of death for certain patients.

Studies of diet–eggs, caffeine and sugar; of screening tests–annual mammograms, PSA testing and lung scans for smokers; even topics as diverse as circumcision or drinking eight glasses of water a day, have all produced conflicting results. How can this happen? How often does this happen?

“We call them reversals,” said Adam Cifu, associate professor of medicine and co-author of a recent research letter on the phenomenon, published in the Archives of Internal Medicine. “Some new therapies are replacements,” he said. “They are better than what came before, as demonstrated by large, well designed, controlled studies.” Other new approaches arrive expecting to become replacements, but biology, complexity and, over time, better studies transform them into reversals.

“They make sense in the laboratory,” Cifu said. “Doctors are eager to try things that should work, based on what we understand about the biology. But the human body is complicated; things that made perfect sense in theory may not work in quite the same way in the clinic. We wanted to find out how often this happened.”

So Cifu and colleague Vinay Prasad, a former Pritzker student and now internal medicine resident at Northwestern, turned to the leading American medical publication, the New England Journal of Medicine. They focused on the 124 articles that appeared in 2009 involving investigation of a new medical practice or a practice already in adoption. Of those 124 articles, 16 could be characterized as a reversal. So 13 percent, one out of eight, contradicted an emerging or accepted medical practice.

The reversals included medical therapies such as tight control of blood sugars for patients in an intensive care unit, invasive procedures such as efforts to reopen clogged arteries for patients with chronic total artery occlusion, and predictive tests such as randomized prostate cancer screening.

One resounding reversal involved back-to-back studies in the August 6, 2009, issue that took a close look at vertebroplasty, a treatment for pain caused by compression fractures of the spine, a common problem for older women. The procedure, which had been widely used for more than a decade, involved injecting bone cement through a small hole in the back into a fractured vertebra. “We spent billions of dollars on this,” Cifu said. Several small early studies implied good results, but there had never been a blinded, placebo-controlled, randomized trial.

However, once NEJM published results from the first such trials, the party was over. One study found “no beneficial effect of vertebroplasty over a sham procedure at 1 week or at 1, 3, or 6 months.” The other reported that results for patients treated with vertebroplasty were “similar to the improvements in a control group.” An editorial in the same issue predicted the procedure, “virtually always considered to be successful,” would now be “considered no better than placebo.”

Cifu and colleagues developed a Why-We-Got-It-Wrong-Initially chart summarizing the reasons behind each reversal.

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A patient in the hospital receives a long line of visitors, from physicians to nurses to medical students to other staff members. The conversations with most of these personnel tends to be mostly business - answering clinical questions or following instructions, with maybe a little bit of small talk squeezed in between temperature measurements and pill swallowing. Deeper conversations of a religious or spiritual nature may be left to hospital chaplains or religious representatives visiting the patient. But with only about two-thirds of hospitals providing pastoral care - and with tightening hospital budgets potentially threatening to push that number even lower - is it possible to measure the value of these spiritual discussions?

That was the aim of a new study by the research group of Farr Curlin, associate professor of medicine at the University of Chicago Medical Center. In an analysis led by medical student Joshua Williams, the team measured how many of over 3,000 patients in a survey reported having a spiritual or religious discussion while they were in the hospital, who that conversation was with, and most importantly, how it affected the patient’s opinion of their experience in the hospital. Published recently in the Journal of General Internal Medicine, the study found that a little bit of attention to a patient’s spiritual concerns boosted patients’ satisfaction with doctors, confidence and trust in their physicians, their feelings about the teamwork between doctors and nurses, and their rating of the overall care received.

“Our data is the strongest data so far that having these issues addressed, even having them brought up, is something that people experience as very positive,” Curlin said. “What’s interesting is it didn’t matter whether the patient said they wanted it, just having had it was associated with higher rates of satisfaction across four different measures.”

Surprisingly, the source of the spiritual or religious conversation was less important than the content. The benefits were the same whether patients talked with a chaplain, a physician, or even a religious figure from outside the hospital, Curlin said. Furthermore, while most of spiritual discussions were originated by chaplains (61 percent), the patient satisfaction figures suggested the good vibes were contagious, spreading out to improve patients’ feelings about the other members of their health care team.

“It was the whole experience: the physicians, the clinical team that took care of them,” Curlin said. “The care they received at the hospital was rated more highly if someone talked to them about spiritual concerns.”

The effect was not limited to patients with strong religious beliefs, or even those who sought out a patient ear for their spiritual thoughts. Forty-one percent of patients said they wanted to discuss such concerns, but even patients who weren’t seeking spiritual counsel but were approached anyway demonstrated the same positive influence upon their experience in the hospital. Curlin said that a benefit even for non-religious patients indicated that the effects of talking to a chaplain (or a physician, or a friendly custodian) were more about being recognized as a person instead of a patient.

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Popular Mechanics typically offers step-by-step guides for changing your oil or building a bookcase. But in a recent feature they seriously upped the instructional ante with an “Extreme How-To” - How to Perform Open Heart Surgery. The expert chosen to guide their readers through this don’t-try-this-at-home process was Medical Center cardiac and thoracic surgeons Jai Raman and Shahab Akhter who helped develop a new technique in heart surgery called the “wrap procedure.” The surgeons do a great job of explaining how the surgery has changed over the years, particularly in the materials used for repairing the heart and sternum after surgery to speed recovery and decrease scarring. “You’ve got to get comfortable putting stitches into a beating heart,” is just some of the sage advice that Raman offers in the piece.

The end of the academic year always brings a bounty of teaching honors, voted on by medical students, residents, and faculty peers. For the 2010-2011 year, more than two dozen awards were handed out by the Pritzker School of Medicine, the Biological Sciences Division, and departments of the Medical Center. For an awards roundup from both sides of campus, visit this article at the University of Chicago News Site.

The pediatric cancer patients at Comer were treated to a celebrity visit last weekend, though their parents and staff may have recognized her more by voice than by sight. Delilah, the easy listening disc jockey known for her “Love Someone” radio dedications, visited families at Comer before making 3-year-old leukemia patient Atia Lutarewych her “Brave Child of the Week.” You can listen to her segment on the visit here [mp3].

Another inspiring story of pediatric cancer was told in the Chicago Tribune this week, focusing on 6-year-old neuroblastoma patient Theofanis Yianas. After Theo’s hair fell out from chemotherapy treatment, 30 friends and family members shaved their heads in solidarity with the young boy. Theo’s doctor, professor of pediatrics Susan Cohn, comments on the importance of support in a patient’s recovery.

What did St. Vitus’ Dance - the 14th century outbreak of weeks and months-long uncontrolled dancing across Europe - have to do with mirror neurons in the brain? UChicago psychologist John Cacioppo weighs in on this fascinating phenomenon for ABC News.

An interesting plan to create “mystery shoppers” for assessing the primary care shortage in the United States was revealed in the New York Times on Sunday, then disappeared by Tuesday after doctors bristled about “snooping.” The survey, which would have been conducted by the University of Chicago National Opinion Research Center, shows how far the administration will go to collect data on the current health care system…and how stiff the medical field’s resistance can be to being measured.

By John Easton

In most clinical trials the targets are patients, volunteers with a disease who sign up for a study to help advance medical knowledge and perhaps lead to better treatments for what ails them. But this week a report in the Archives of Internal Medicine revealed that sometimes the real targets are not so much the patients as the physicians who treat them.

The doctors who agree to participate as investigators in such a trial almost never find out that that they are the trial’s subjects, the ones being studied. Studies of this sort are known as “seeding” trials–kind of like seeding a cloud with particles in order to produce precipitation. The goals of a seeding trial extend beyond measuring the safety or efficacy of a drug to persuading - some would say hoodwinking - the hundreds of doctors who take part in the study to prescribe the drug and become rainmakers for a drug company. So much for informed consent.

Such matters “seldom see the light of day,” explained Caleb Alexander, associate professor of medicine at the Medical Center, who wrote a commentary to accompany the Archives paper, which was authored by researchers at Brown and Yale Universities. “One might think that seeding trials should be illegal,” he said. “They are unethical. They are not illegal.”

No one knows how often this happens. There is only one other recent, well-documented case and it required a lawsuit to come to light.

In this case, the lawsuit was triggered by accusations that the drug gabapentin - AKA Neurontin, approved by the FDA in 1994 for use to control seizures and in 2002 for nerve-related pain - was being marketed for off-label uses, such as for psychiatric disorders. The suit opened the vaults, allowing plaintiff’s lawyers broad access to the drug makers’ marketing plans, eventually resulting in hundreds of millions of dollars in fines.

One small part of the drug’s history was the STEPS trial, short for Study of Neurontin: Titrate to Effect, Profile of Safety. This was an uncontrolled, unblinded trial, launched after FDA approval. It enlisted 772 investigators, many with little or no clinical-trial experience, and 2,759 patients. Even before it began, there were questions about the design. After it was completed, there was the lawsuit, and then there were documents - more than 3,000 of them - correspondence, memos, presentations, market research. The researchers focused on about 400.

What they found met all the requirements for a seeding trial, as spelled out in a 1994 article in the New England Journal of Medicine (PDF) by former FDA commissioner David Kessler and colleagues. “Some company-sponsored trials of approved drugs appear to serve little or no scientific purpose,” they wrote. They are, instead, “thinly veiled attempts to entice doctors to prescribe a new drug being marketed by the company.”

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Countless campaigns have been launched to steer schoolchildren toward healthy habits, and yet rates of childhood obesity and diabetes continue to soar. Celebrity endorsements, catchy catchphrases, and food pyramid redesigns have struggled to combat the allure of fast food and television in the battle for child health in the United States. But with childhood obesity rates tripling in the last 30 years and type 2 diabetes showing up earlier in life, there’s an urgent need for more effective programs to promote nutrition and exercise in kids. One strategy is to create more relevant programs, locally focused and tailored to the culture of the children the program is trying to help.

That approach inspired not one but two child diabetes prevention programs created by Medical Center researchers and tested with our neighbors on Chicago’s South Side. The two programs - called Reach-Out and Power-Up - are siblings, with similar designs, goals, and measures, but in slightly different populations and venues. The pilot studies, both published in recent months, demonstrate the challenges faced by researchers in creating effective, reproducible programs with a local focus…and also offer hope that a successful intervention is possible.

Before the programs could be designed, the first step was to listen. The research team, led by Deborah Burnet, professor of medicine and pediatrics, organized focus groups with overweight children and their parents to learn about their specific obstacles to improving health and gather ideas about the types of physical activity and classes that would appeal to them. For example, the African-American children said they would like to try martial arts and yoga, so instructors for those activities were recruited. The conversations laid the groundwork for programs that would take the unique circumstances of families on the South Side of Chicago into account.

“Nutrition and exercise are both behaviors we do in a social context; in a place, in a neighborhood, in the context of certain social mores and expectations and cultural factors,” Burnet said. “Food, especially - who cooks, where we learn how to cook, how do our tastes get shaped in what we like to eat - those occur in social and cultural contexts.”

While both programs were designed to improve the health and behavior of children, the targets were both the kids and their parents. In Reach-Out, families gathered at a local YMCA for 14 weeks, splitting into separate parent and child groups for the first part of each session and then reconvening for a combined activity. Sessions included grocery store tours, exercise training, cooking classes, and even a family basketball game. Scavenger hunts, relay races, and Family Feud-style review quizzes were used to keep the kids and their parents engaged. But addressing the family’s cooking and eating habits could also be a sensitive topic.

“Feeding is all bound up with caring and love, so it’s very complicated - if you tell grandma she’s not cooking for her grandchildren right, her feelings get hurt,” Burnet said. “So how do you do that in a constructive way so that grandma is valued, but also moves in this healthy direction?”

At the end of the Reach-Out pilot study, published in the Journal of the National Medical Association, the program earned glowing reviews from participants, who said that it helped reduce food intake, steered them toward new fruits and vegetables, and encouraged increased physical activity. However, the clinical improvements were modest, including slight dips in BMI z-score (which scales the measure to child age) and glucose-to-insulin ratio. The incremental changes might mean that very heavy kids need more help to get back to healthy habits, Burnet said: “Kids who are this big probably need a more intensive treatment and intervention than a weekly community-based program.”

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