Designing a trial for the treatment of cancer is hard. Designing a trial to prevent cancer is even harder. In a typical population, such a small percentage of people will naturally contract a particular type of cancer that to test the ability of an intervention to reduce that number may require tens of thousands of subjects to be followed for decades. That’s not a cheap, or easy, study to run.

But in a population where the risk for a particular cancer is elevated, a prevention study might be both possible and immediately helpful. One such situation is found in the unfortunate case of Bangladesh, where charity efforts in the 1970’s to provide pathogen-free sources of drinking water accidentally exposed 40-70 million people to water tainted with arsenic. The disease epidemiology of that long-term exposure was recently characterized by Habibul Ahsan, director of the Center for Cancer Epidemiology and Prevention at the University of Chicago Medical Center, whose HEALS study found increased mortality and cancer in a study of more than 20,000 people.

In addition to characterizing what has been called “the largest mass poisoning of a population in history,” Ahsan has also been leading a study to try and offset some of its damage. The Bangladesh Vitamin E and Selenium Trial, or BEST, is testing two inexpensive nutritional supplements for their ability to prevent the non-melanoma skin cancer (NMSC) that commonly develops in people exposed to high levels of arsenic. The study, which recently received a $10 million renewal from the National Institutes of Health, has a twofold purpose, Ahsan explained.

“In the short term as well as unfortunately the long term, these people will be at an increased risk for arsenic-related cancers,” Ahsan said. “What we can do on the biomedical side, beyond solving the arsenic-contaminated water problem, is to identify low-cost, pharmacological or dietary/nutritional interventions. Something we can provide to these people that is feasible for millions of people at risk to take and reduce their future risk of these cancers.”

Like Ahsan’s HEALS project, the BEST study is massive in scope. In the first five years of the trial, roughly 7,000 Bangladeshi subjects were recruited and sorted into one of four groups, each required to take one pill a day for 6 years. Depending on the group, each subject will take a daily dose of vitamin E, selenium, vitamin E and selenium, or a control pill, with researchers tracking the amount of skin cancer, mortality, and other adverse events that develop by the end of the study.

Even at that size, the trial is smaller than it would be in a less vulnerable population. Because of the increased risk for NMSC among Bangladeshis exposed for decades to arsenic, a chemoprevention trial can operate with fewer subjects, Ahsan said. The infrastructure built by Ahsan’s team in Bangladesh (with collaborators at Columbia, Dartmouth, and the University of North Carolina) also saves money and ensures high compliance rates. More than 300 staff members have been hired to visit each subject on a daily basis to make sure they take their pill and to observe any side effects or illnesses.

“That’s something that’s impossible to do here,” Ahsan said. “It’s an expensive trial, but it’s a fraction of the cost had we conducted this trial here in the United States.”

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Losing weight can be described at its simplest as a matter of counting calories during the daytime. Consume fewer calories and burn more through activity and exercise, and you’re likely to lose weight. Eat more high-calorie foods and sit on the couch all day watching football, and you get the opposite effect. But according to a new study from University of Chicago Medical Center researchers, another number should be taken into account by dieters: hours of sleep.

Given people generally do not eat or exercise while asleep (aside from some Ambien users), the link between weight and sleep may seem unlikely. But previous research at the University of Chicago found that sleep loss can wreak havoc with a person’s endocrine system, the hormones that control appetite and metabolism. In a 2004 study, men limited to only four hours of sleep a night reported increased appetite and showed hormonal changes consistent with increased hunger - increased ghrelin, which signals hunger, and decreased leptin, which signals satiety. But the long-term influence of those sleep pattern changes on weight gain or loss remained to be studied.

Monday, an experiment testing that connection was published by Plamen Penev, assistant professor of medicine, and colleagues in the Annals of Internal Medicine. And this was no easy experiment: 10 subjects had to spend two 14-day periods essentially living in a laboratory, so that scientists could control their diet, their daily activity, and the amount of sleep. But the small study reached a compelling, unexpected conclusion.

On the surface, the results may look disappointing. Subjects were allowed 8-1/2 hours in bed during one two-week period, and limited to 5-1/2 hours in bed the other two weeks. Diet and exercise were kept the same between the two periods, so that the effect of sleep alone could be isolated. But when the researchers looked at weight loss during the two periods, it was almost identical. Subjects lost about 3 kilograms, or 6 pounds, over the two weeks, whether they were getting a long night’s sleep or the reduced amount.

But not all weight loss is created equal. When the researchers looked more closely at what kind of weight was lost over the two-week periods, an important difference was revealed. With adequate sleep time, more than half of what was lost was fat. But when sleep was limited to less than 5-1/2 hours, only a quarter of the lost weight was due to reduced fat, suggesting that important protein and muscle were being shed instead of unsightly flab.

“If your goal is to lose fat, skipping sleep is like poking sticks in your bicycle wheels,” Penev said. “Cutting back on sleep, a behavior that is ubiquitous in modern society, appears to compromise efforts to lose fat through dieting. In our study it reduced fat loss by 55 percent.”

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It’s great to have a treatment that’s proven to work in a difficult psychiatric condition such as anorexia nervosa. It’s even better to have two treatments for such a disorder. But having multiple options also creates a quandary for psychiatrists: with a new patient, which treatment do you try first? Creatures of habit like the rest of us, many doctors will simply stick with the method they know best until given convincing evidence that it’s worth switching gears. To be the new treatment of choice, a method must beat out the current champion in a head-to-head battle.

One such comparison, conducted by researchers at the University of Chicago Medical Center and Stanford University, was published yesterday afternoon in the Archives of General Psychiatry. The trial compared the most common form of treatment for adolescents with anorexia, known as adolescent-focused therapy (AFT), with the newer, family-based treatment (FBT), also sometimes known as the Maudsley Approach. The latter name comes from the Maudsley Hospital in London, where Daniel Le Grange, now director of the Eating Disorders Clinic at the University of Chicago, helped develop a new approach to bringing anorexic teens back to healthy weight and eating habits.

Under adolescent-focused therapy, the therapist works directly with the patient on a one-to-one basis, emphasizing the importance of weight gain and helping them accept personal responsibility for healthy eating. Family-based treatment, as you might expect from the name, does more to incorporate the parents into that process, equipping the patient’s mother and father with the tools to encourage healthy eating at home. By doing so, the therapist hopes to avoid hospitalizing the patient while permanently adjusting the home environment, removing factors that could lead to relapse after therapy is completed.

“No one is more available to care for the kids than the parents are; no one would put the time aside in the way that parents would, and no one loves their kids more than parents do,” Le Grange told NPR’s Morning Edition (where you can also hear the perspective of one patient’s mother on family-based treatment).

The two therapies had been compared previously, but in smaller studies with only two or three dozen patients. True convincing evidence requires a randomized trial, with enough patients for the statistics to make a strong case for one of the treatments. So, combining forces between Chicago and Stanford, Le Grange and his collaborator, James Lock at Stanford, were able to gather 120 patients with anorexia nervosa (with an average age of 14-1/2) for the study.

Split evenly between FBT and AFT, the patients were followed for a year of therapy and another year of follow-up. At the end of treatment, 42 percent of those enrolled in FBT showed full remission back to at least 95 percent of expected body weight, compared to only 23 percent of those enrolled in AFT. While that comparison fell just short of statistical significance, with a p-value of .055, Le Grange said that the higher standards used in the study spoke to the effectiveness of FBT.

“We used the higher yardstick for remission of 95 percent of body weight, which we felt was clinically more appropriate,” said Le Grange, a professor of psychiatry and behavioral neuroscience.

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Many people consider human evolution to be a done deal, something that happened in our distant, wild past. But as Nicholas Wade wrote last week in the New York Times, there is increasing scientific evidence that natural selection has continued to act upon humans, producing observable evolutionary changes as recently as 3,000 years ago. Studies have found that everything from high altitude tolerance in Tibet to dry earwax may have evolved in relatively recent human history, producing subtle but significant population differences in the frequency of certain rare gene variants.

One of the genetic approaches cited by Wade in his article is the work of Anna Di Rienzo, professor of human genetics at the University of Chicago. In a paper published earlier this year in the Proceedings of the National Academy of Sciences, a group from Di Rienzo’s laboratory led by graduate student Angela Hancock went looking for recently evolved human genes in an unusual way. Their results uncovered new ways humans evolved in the recent past, with consequences still felt in our modern age of obesity.

Many genetic studies take an intentionally “naive” approach to such a genetic hunt, comparing gene variants between regional populations with no preconceptions so as not to bias the data. But sometimes a little bias doesn’t hurt; in fact, it may help find differences that fall through the cracks of a broad, unbiased sweep. Hancock and colleagues hit upon the idea of filtering their comparisons by predictable selective pressures expected to drive evolution, such as ecology and diet.

“A lot of the studies done before have been done in a way that was sort of agnostic to the selective pressure,” Di Rienzo said. “We are using aspects of human environments to learn about natural selection and the way humans adapted specifically at genetic level. We use genetic as well as ecological data, and we think that this combination allows us to tap into a set of genetic adaptations that are not accessible by other studies.”

To do this, the team took a particular variable expected to drive evolution, such as polar ecoregion. Because modern humans first arose in the tropical temperatures of Africa, those populations who migrated to a colder environment would be expected to need dramatic genetic changes to survive. So the researchers (using data from the Human Genome Diversity Project, the International HapMap Project, and their own original sequencing) compared the genomes of polar populations against non-polar populations, to see if it revealed specific gene variant differences.

Indeed it did. Several genes were found to appear at different frequencies in the polar populations, and most were found to have the kind of function one would expect to be selected for in a cold environment. Genes that helped people regulate body temperature, for instance, were more likely to have changed in a polar population. Energy metabolism also appeared to have been selected for, with the genes for enzymes that degrade sugars showing differences. The results lined up nicely with a 2008 paper by Hancock and colleagues that used a different analysis method to detect a relationship between climate and genes associated with metabolic disorders.

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ED and STDs: Unfortunate Acronym Bedfellows

With the constant drumbeat of advertisements for erectile dysfunction drugs, most of us can probably recite the list of precautions and side effects by heart by now. Though some of them inspire juvenile giggling (the one about “lasting more than 4 hours,” in particular), one warning is a head-scratcher: “does not protect against sexually transmitted diseases, including HIV.” Saying so always struck me as sort of a “duh” statement, but there had to be a reason for it to be there as part of the FDA-mandated laundry list of disclaimers for pharmaceutical advertising.

Indeed, there have been some studies that suggest men using ED drugs are at higher risk for STDs, which makes sense if you consider they will presumably be having more sex. But a new study in Annals of Internal Medicine of the STD rate in older men both before and after they receive a prescription for ED medication indicates that it’s not so much the drug, but the patient. The authors, which include Amee Kamdar of the University of Chicago Booth Graduate School of Business, analyzed the insurance claims of nearly 1.5 million men older than 40, comparing the rates of diseases such as HIV, chlamydia and syphilis in those who did or did not receive a prescription for an erectile dysfunction drug.

Those who sought treatment for ED did indeed have roughly twice the STD rate of the control population. But when those numbers were broken down into the year before ED prescription and the year after, the STD rate and risk was unchanged for those who received the drugs. That finding suggests that treatment of ED is not responsible for riskier sexual behavior, but people who engage in risky sexual behavior are more likely to seek treatment for ED. “The observed associated between ED drug use and STDs may have more to do with types of patients using ED drugs rather than a direct effect of ED drug availability on STD rates,” the authors conclude.

Clinically, the paper adds further argument for improved discussion of sexual issues with older patients, a topic covered previously on the blog regarding the research of our own Stacy Tessler Lindau. Studies have found that only 9 percent of adults between the age of 40 and 80 discussed sexual health with their physician during a routine visit, and opinion pieces (one called “Time for ‘the talk’ - again”) have argued that doctors should monitor the sexual practices of aged patients as much as younger ones. As the new study shows, when patients “talk to their doctor about ED,” the doctor should talk back about STDs.

What a Fumbled Handoff Looks Like

Last week, as expected, the Accreditation Council for Graduate Medical Education recommended further restrictions on the number of hours that medical residents can work. Under the new guidelines, first-year residents will not be allowed to work for longer than 16 consecutive hours (as opposed to the occasional 30-hour shift today) and more direct supervision by older residents and attending physicians will be required. The new guidelines are not yet settled - there’s a 45-day public comment period currently underway - but there is already plenty of research into the pros and cons of further restricting a resident’s time in the hospital (we’ll have more coverage of the guidelines debate soon).

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Attaining a healthy weight is often billed as an individual pursuit, with television commercials eagerly encouraging customers to take hold of their habits. But for all the calorie-counting and exercise schedules you can give a person, their struggle with weight doesn’t occur in isolation. Family members and friends can negatively influence your diet, whether it’s meals at home or dining out, and your activity levels - encouraging a night at the bar instead of an hour on the treadmill.

But those external influences can also be harnessed for good, as a front page article by Julie Deardorff in the Chicago Tribune showed yesterday. Deardorff focused on the Maudsley Approach, a family-based treatment for anorexia and bulimia that involves the parents or other relatives in encouraging the patient to eat. That strategy is a shift from the traditional treatment for eating disorders, which usually involves a one-on-one inpatient program designed to convince the patient to regain healthy eating habits. But the Maudsley Approach, designed in part by University of Chicago psychiatrist Daniel Le Grange, has evidence on its side: trials, such as this one, that showed better outcomes with family-based treatment compared to traditional psychotherapy.

I spoke to Le Grange about the Maudsley Approach and other research trends for our Dr. FAQ video series in March; here’s the video that most directly focuses on family-based treatment.

While family appears to be a useful tool for positively changing the diet of someone with an eating disorder, there is also a dark side to the familial influence on food habits. Study after study has found that obesity runs in families, through an as-yet-undetermined interaction of genetics and environmental factors. Even in families where one member undergoes a surgical procedure for their obesity such as gastric bypass, the ripple effects through their family remain.

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General internal medicine might seem like an awfully vague term. But assuming the health care reform bill signed by President Obama in March will be fully implemented, the general internists will finally have their day. Many of the bill’s provisions are focused on a reshuffling of the American medical landscape, which is currently dominated by sub-specialists focused on one organ system. In recent years, fewer medical students have chosen to pursue lower-paid and less glamorous careers in internal medicine, leaving a worrisome shortage in primary care doctors and hospitalists just as 32 million uninsured Americans are about to go on the books. The spotlight is about to focus on internal medicine.

“About time,” would probably be the response from most of the doctors assembled in Minneapolis last week for the 2010 Society for General Internal Medicine national meeting. Over three days, thousands of internists met in discussion groups and research panels to chart the course for a new age of American medicine. Though some fears were expressed about how an already overwhelmed system would be able to deal with the new influx of patients, the conference was more focused on seizing the opportunity to rehabilitate U.S. primary care and bring medical services to those who are traditionally underserved. The urgency of the moment was expressed right in the caps-lock and exclamation point of the meeting’s theme: “Value(s)-based generalism: THE TIME IS NOW!”

Of course, many of these efforts to expand the net of primary care didn’t start when Obama used 22 pens to sign the health care bill on March 23rd. Many of the presentations by University of Chicago faculty at the conference discussed pilot programs already being tested to improve the care of those who have traditionally fallen through the health care cracks, efforts to reduce disparity that may be instructive as the reform measures fall into place.

A workshop moderated by Marshall Chin, professor of medicine, presented four examples of programs funded by Finding Answers, Chin’s Robert Wood Johnson Foundation-supported group for studying racial and ethnic health disparities. Chin said the mission was to “evaluate interventions that reduce racial and ethnic disparities,” and the short presentations showed the breadth of that mission. Projects using cultural awareness training, electronic medical record software, and pay-for-performance programs were all discussed as potential solutions, with researchers from Harvard, Brigham and Women’s Hospital and Baylor outlining projects currently underway. One fascinating approach, described by Barbara Turner from Penn, employed African-American patients who had successfully controlled their high blood pressure as “peer coaches” to help fellow patients struggling to adhere to treatment - an elegant way of using community bonds to spread healthy messages.

Another successful example of community health intervention was presented in tandem by Deborah Burnet, section chief of internal medicine at the Medical Center, and Lorri McClinton-Powell, a teacher from Woodlawn Elementary School on the southeast side of Chicago. Last year, Burnet and colleagues conducted a pilot study of the POWER-UP program, an anti-obesity effort based around after-school activities for children and parents, with 40 children and their parents at Woodlawn. Fourteen weekly sessions - focused on themes such as “Muscle Mania” and “Stop & Shop” - taught the children about healthy eating, exercise, and behavior at restaurants and grocery stores. Though small, the study’s results held promise, with declines in overall body mass index among all but the heaviest kids at baseline. The group is currently working with Chicago Public Schools on the possibility of expanding the program for a larger study, Burnet said.

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Illustration from BMJ by Brendan Halyday

Is Santa Claus a risk factor for obesity, swine flu and drunk-driving? And if you saw such a headline, would you think it was a joke?

That’s the cautionary tale floating about on this (admittedly slow) science news week, as a scientific article in the esteemed British Medical Journal entitled “Santa Claus: a public health pariah?” kicked up a bit of a storm. An AP story on the paper, which describes it as “light-hearted research” deep in the story, nevertheless seemed to play the findings of epidemiologist Nathan Grills straight, amusingly when it contained conclusions such as “Santa is a late adopter of evidence-based behavior change and continues to sport a rotund, sedentary image.”

The actual paper is, sadly, subscription-only and unlinkable, but from the text excerpted on the BMJ website, it’s hard to believe that people weren’t tipped off by the author citing Fast Food Nation and Super Size Me in the second paragraph. The AP article, hilariously, cites Grills’ finding of a “very high Santa awareness,” his suggestion that Santa should swap out fireplace cookies for carrots, and his personal experience with the disease-spreading potential of traditional Santa visits.

More disturbingly, Grills said Santa’s close-up contact with sniffling, coughing kids made him a one-man outbreak waiting to happen, with swine flu the biggest seasonal concern.

“Unsuspecting little Johnny gets to sit on Santa’s lap, but as well as his present, he gets H1N1 influenza,” Grills warned.

Grills said he donned a Santa suit himself - and deemed the experience a public health nightmare. “I was kissed and hugged by snotty-nosed kids at each performance and was never offered alcohol swabs to wipe my rosy cheeks between clients,” he wrote.

Okay, so maybe the AP was in on the joke, but according to this Newsweek article, many commentators skimmed over the “light-hearted research” part and wrote scathing replies to Grills’ “findings,” inevitably lumping it in with the ridiculous “War on Christmas.” The bulk of that punditry seems to have been written off the press release (or the AP story), without bothering to check the clearly marked-as-satirical original journal article - another example of a troublesome trend in a journalism industry with fewer and fewer specialized science journalists. Missing some sly Australian humor in a British science journal is harmlessly embarrassing, but relying on intermediaries with an agenda to explain a science finding related to climate change or health care costs is a whole different animal.

Hopefully, the whole silly episode is a holiday lesson for journalists twice over: 1) always check the original article and 2) yes, Virginia, scientists do have a sense of humor.

The latest in our video series where experts from the University of Chicago Medical Center answer frequently asked questions about popular medical topics. To suggest a topic or a question, please contact the editors.

As much a part of modern holiday tradition as presents, parades and parties is the New Year’s resolution to lose weight, a yearly pledge motivated by over-eggnogging and a pained look at the scale. In 2006, a Wall Street Journal poll found that about a quarter of adults who make a New Year’s Resolution pledge to lose weight, exercise more and eat better - the most popular resolution grouping. Now if everyone was successful in their resolution, you might expect that percentage to drop, but January’s goals often fade away as the calendar pages flip through the months.

To hear some ideas about how people can break out of that New Year’s Resolution diet cycle, I went to Mary Russell, a dietitian and director of nutrition services at the University of Chicago Medical Center. Russell said she has heard all the questions about how to start a successful diet, and said that if she knew all the answers she’d be a billionaire. But in our video conversation, Russell shared a number of useful and easy-to-implement tips for making this year’s weight-loss resolution stick, such as keeping a food diary, reducing portion sizes, and planning your grocery shopping around healthy options on sale.

One interesting thread (expanded upon in the third video below) was Russell’s discussion of how the concept of “the healthy diet” has changed over the past few decades. Each year seems to bring another trendy diet that claims to have unlocked the secrets of weight loss through emphasizing certain types of food over others, and Russell warns against these “magic food” diets. But the classic concept of losing fat via low-fat foods has been modified somewhat, most dramatically by the “Mediterranean diet“: the usual fruits and vegetables, but also “healthy fats” such as fish, nutes, olive oil or canola oil, and - most excitingly for some - moderate portions of red wine. Unlike a lot of fad diets, the Mediterranean diet has held up to scientific scrutiny - this New England Journal of Medicine article found twice the weight loss with a Mediterranean diet versus a traditional low-fat plan.

Enjoy the clips, and as Russell says, start thinking about changing eating habits now, rather than waiting for the arbitrary January 1st to shift into a healthier lifestyle.

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