December 14, 2012
NIH Podcast Episode #0174
Balintfy: Welcome to episode 174 of NIH Research Radio. NIH Research Radio bringing you news and information about the ongoing medical research at the National Institutes of Health – NIH…Turning Discovery Into Health®. I'm your host Joe Balintfy, and coming up in this episode NIH scientists have used reality TV to help understand the impact of diet and exercise used together, a personal perspective on taking science-based techniques to the classroom, and details on understanding cancer screening. But first, this news update. Here’s Craig Fritz.
Fritz: An NIH clinical trial will examine an investigational tuberculosis drug. In 2011, 8.7 million people worldwide became infected with tuberculosis, and 1.4 million people died. Scientists say that new, simplified treatments that cure tuberculosis more quickly are desperately needed, and it has been nearly 50 years since a new drug specifically developed for the disease was licensed. This is a relatively small study, but researchers hope it yields insights into whether this investigational drug shows promise in people who are newly diagnosed with tuberculosis.
In another NIH clinical trial an experimental drug for depression was studied. The drug works similarly to the fast-acting antidepressant ketamine, but with few side effects. Patients reported briefly improved depression symptoms in minutes and the improvement lasted for over an hour. Ketamine also works quickly, but its usefulness is limited by its potential for dangerous side-effects, including hallucinations. It is being studied mostly for clues to how it works. Existing antidepressants available through prescription take a few weeks to work, imperiling severely depressed patients, who can be at high risk for suicide.
For this NIH news update – I’m Craig Fritz.
Balintfy: News updates are compiled from information at www.nih.gov/news. Coming up, research on Aspergers Syndrome applied in a classroom, insight into cancer screening, and how the “Biggest Looser” realty TV show helps researchers. That’s next on NIH Research Radio.
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“Biggest Loser” study finds diet and exercise can sustain weight loss
Balintfy: Researchers have studied the effect of daily strenuous exercise and a restricted diet by examining data from a reality TV program. Wally Akinso has the story.
Akinso: According to an NIH study, an exercise and diet combination is more effective for weight loss than just dieting alone. Researchers used data from the reality TV program “The Biggest Loser” for the study.
Hall: It's actually studying season eight of “The Biggest Loser” contestants.
Akinso: Dr. Kevin Hall is from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the NIH, and he's the senior investigator of the study.
Hall: The way we got involved in this study was as most of the viewers who have ever watched the show probably knows that people step on scales at the end of the week and seem to be losing substantial amounts of weight — really surprising amounts 10, 15, 20 pounds per week, which is much greater than we typically see in weight loss programs.
Akinso: Dr. Hall explains that the shows' contestants were voluntary participants in the study.
Hall: So we went out to California during season eight with a group of investigators to really try to understand better what was going on metabolically when these obese participants were participating in this pretty intensive lifestyle intervention to lose substantial amounts of weight over a short period of time.
Akinso: Researchers measured body fat, total energy expenditure and resting metabolic rate — the energy burned during inactivity.
Hall: So I really wanted know, how many calories were they burning? How many calories were they eating? How much of the weight that is being lost is fat tissue versus lean tissues like muscle and things like that? So we got involved with the physician responsible for the care of the contestants on the show. And designed a study to go out there and measure changes in body composition, that's how much fat mass versus lean mass, is being changed as a result of this intervention as well as how many calories in total they're burning but before they started the program at six weeks into the program as well as at the end of the competition phase which is about seven months after they started.
Akinso: Dr. Hall used a mathematical computer model of metabolism — currently intended for research conducted by scientists and health professionals — to calculate the diet and exercise changes underlying the observed body weight loss.
Hall: What my lab at NIDDK is interested in doing is building computer simulation models of how we can put these data together in a way that helps us better understand the physiology of weight loss, the physiology of metabolic change as well as the physiology of how the body fat verses lean tissue is regulated.
Akinso: Because the TV program was not designed to directly address how exercise and diet interventions each contributed to the weight loss, the computer model simulated the results of diet alone and exercise alone to estimate their relative contributions.
Hall: Once we put the data together in our model and we tested the model to see if it was accurately matching data and which it was we then could run some what if scenarios and say what if instead of them doing both the exercise and the diet, what if they only did one or the other. And so we ran that simulation and we found that the diet alone would actually have led to more weight loss than exercise alone but actually less fat loss. And there were a couple of reasons for that one is because exercise really helps preserve that lean tissue that muscle tissue. And as a result the exercise its self is also burning calories as well. And so while you don’t lose as much weight with the exercise alone you lose more fat compared to if you just done the diet alone and stayed a sedentary lifestyle.
Akinso: More than two-thirds of U.S. adults age 20 and older are overweight or obese, and more than one-third of adults are obese. Being overweight or obese can lead to type 2 diabetes, heart disease, high blood pressure, stroke and cancers. For more information on this study, visit www.niddk.nih.gov. For NIH Radio, this is Wally Akinso For NIH Radio, this is Wally Akinso.
From Clinical Trials to Classroom Commitment, NIMH Expertise Benefits Students
Balintfy: Volunteering for a clinical trial is not typically done through a reality TV program. Many times, patients and their families are looking for ways to get the most health benefit they can. In this case, a story brought to us by Jim McElroy at the NIH’s National Institute of Mental Health, parent Lisa Greenman describes her experience, and that of her son, who has Aspergers Syndrome, an autism spectrum disorder that is milder than autism but shares some of its symptoms.
Greeman: You know, I think participating in the research at NIMH has had an enormous beneficial impact on my family.
McElroy: The research Lisa Greenman talks about was an NIMH clinical trial for children with Aspergers Syndrome- children like her own young son… who was seven years old at the time. NIMH researchers had developed an exercise designed to mitigate frustration in children by teaching them relaxation techniques.
Greenman: He had just aged into eligibility for a study that was a medication trial and what we learned from our participation in that study shaped his future in all kinds of ways. It really taught me about the importance of understanding social learning and the ways in which brain differences might affect social learning. I got a better understanding of the significance of anxiety and the way it affects behavior. The importance of having a high degree of structure and predictability in the environment.
McElroy: Lisa wondered why these science based techniques couldn’t be used in special education classrooms. And it was a question she wanted to ask educators at Ivymount- a highly regarded special education school in Rockville Maryland.
Greenman: I ended up coming together with a group of clinicians from the community and parents of kids in the community and approaching Ivymount, and asking them- well, begging them really- to start a program that would take what they had at their core and graft onto it this cognitive piece, you know, providing an academic program that was appropriate for kids who had average to above average to, you know, really extraordinary intellectual abilities. I came out of the study at NIMH with a really strong sense of what was needed for my child and an understanding, uh- you know I’ve been a public defender for 25 years and so I’m, you know, out there in a community that’s not as well resourced as my own family. And I know that if there’s something that’s not available for my child and I’m able to look every for it that there are lots of people who have this need as well.
McElroy: Eventually, Ivymount said yes to implementing the science based techniques Lisa and her family had experienced at NIMH.
Greenman: I say that when we were in this study at NIMH we got better care than money can buy. There isn’t a way that you can go out into the community and purchase the quality of care that my son and our family received there. I mean I was incredibly grateful to these folks and would just, you know, walk through fire for them.
Balintfy: Again that’s Lisa Greenman and you heard from Jim McElroy at NIMH. For more information about Aspergers Syndrome and participating in autism spectrum disorder clinical trails, visit www.nimh.nih.gov. And be sure to tune into our next episode when I bring you an audio-documentary of my 5-day experience as a healthy volunteer for a clinical trial. But coming up in this episode, understanding the risks and benefits of cancer screening. That’s next on NIH Research Radio.
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The science behind cancer screening
Balintfy: Some types of cancer can be found before they cause symptoms. Checking for cancer, or for conditions that may lead to cancer, in people with no symptoms is called screening. I’m talking with Dr. Barry Kramer, director of the division of cancer prevention at the NIH’s National Cancer Institute about this and ask, what is the goal of cancer screening?
Kramer: The goal of screening is to detect cancers that would be easier to treat and particularly to change the outcome. In other words, it’s not just enough to detect the cancers early, you’re looking for the cancers that would have caused problems and are lethal in potential hoping to pick them up at an earlier point in their development at a time when they can be treated and the death from the cancer averted.
Balintfy: Screening is a tool that’s used not just for cancer. But are there some particular challenges or difficulties specific to cancer screening?
Kramer: There certainly are in part because not all the cancers that we detect are lethal and yet under the microscope they look similar enough to the lethal cancers that they have to be treated. Therefore, in cancer screening, probably out of proportion to some of the other diseases for which we screen, you have to anticipate an element of over diagnosis. That is detecting nonlethal cancers that nevertheless are treated very aggressively as though they were lethal cancers.
Balintfy: How then Dr. Kramer, would you summarize the benefits and risks of cancer screening?
Kramer: So the most clear and important benefit of screening is picking up cancers in an earlier stage that would have caused death and averting that death. So the clearest example of a benefit is reducing the risk of dying of the target cancer. At least for some people, there is a potential benefit of reassurance. That is offering people who are healthy, who feel healthy a test that can reassure them that they are in fact healthy. But that is a softer, positive outcome because most people who feel healthier are actually healthy and therefore the added information that they get from a negative screening test when they feel healthy is very small.
On the other hand, there are some downsides. There can be false positives, that happens quite commonly with a variety of screening tests. So the person without cancer actually has a positive test and therefore they have to go through the fear, the false alarm, and the anxiety of going through workups in the fear that they may actually have cancer when they don’t.
On the other side of the coin, there is a less common but worse harm of screening that’s referred to as over diagnosis. That is a positive test in someone who actually has a cancer or something that a pathologist would be willing to call cancer but the cancer isn’t lethal. In that circumstance, unlike the false positive where after the workup the person is reassured that they don’t have cancer, the person is told in the case of over diagnosis that they have cancer. But if it is a nonlife-threatening cancer, they nevertheless have to undergo the treatment which sometimes includes major surgery, radiation, chemotherapy, hormone therapy, all of which have their risks. So the more common harm of screening is a false positive but the more serious harm is over diagnosis. As we look more and more carefully for over diagnosis, we find that it is actually a more common phenomenon than we traditionally assumed.
Balintfy: Sometimes the screening test itself has some risks too, doesn’t it?
Kramer: Absolutely. So there are simple screening tests that carry almost no harm in and of themselves. The PSA test for prostate cancer is an example where it’s just a blood test. The harms are the events that occur after the prostate test from the false alarms and from the over diagnosis. But other screening tests have a harm in and of themselves, the tests that have radiation associated with them. The more diagnostic x-rays we use, the more cancers that we’re going to incur. Then the diagnostic workup can carry a lot of harm too. So that a helical CT-scan in a smoker can show an abnormality that may trigger some very aggressive diagnostic workup including major surgery. In the case of colonoscopy, you can actually perforate the colon accidentally and that happens the older a person is when they undergo their colonoscopy, the higher their risk of perforation. So in that case albeit rare, there is as serious harm that can come from the screening test itself.
Balintfy: What are some of the most common cancer screenings that are available today?
Kramer: There are a whole variety of tests that are available and they have varying degrees of evidence associated with them. So the first screening test that was put in to common use is one that is a proven benefit and that’s screening for cervical cancer and for decades we’ve been screening with Pap smears and that’s known to substantially reduce the risk of dying of cervical cancer. No one questions the utility of cervical cancer screening.
Likewise randomized controlled trials have proven the worth of screening for colorectal cancer. Most particularly the earliest test that was shown to decrease the risk of dying of colorectal cancer was with fecal occult blood test, testing for blood in the stool that you couldn’t see. More recently randomized trials have proven the efficacy of endoscopy specifically 60-cm flexible sigmoidoscopy.
Other tests that are proven to be of value, albeit with tradeoffs that we’ve been talking about, very recently we’ve shown that low dose helical CT in heavy smokers and former smokers does reduce the risk of dying of lung cancer. So those are proven tests.
Mammography has also been show to decrease the risk of dying of breast cancer, although there is increasing debate about the tradeoffs and what age is the best age at which to start screening. Some organizations will recommend screening every year starting at age 40, others will recommend screening every other year at age 50. But I think more and more organizations are starting to realize that there are some tradeoffs that we hadn’t recognized before, specifically the harms of over diagnosis.
There are finally tests that are in common use but have very little evidence behind them to prove a net benefit. In particular, the PSA screening test, which is very commonly used in adult men, has been shown to have substantial harms associated with it but we don’t proven benefit and that’s why the US Preventive Services Task Force has concluded that it should not be a routine part of medical practice. The same is true for screening for ovarian cancer in which National Cancer Institute sponsored trial looking at transvaginal ultrasound plus bimanual examination of the ovaries plus a blood test referred to as CE-125 did not decrease the risk of dying of ovarian cancer but again has substantial harm associated with it because it led to a lot of operations for abnormal tests.
Balintfy: So Dr. Kramer what kind of advice or recommendations can you give overall? Is it basically going to be a personal decision for the patient after a discussion with their doctor?
Kramer: Yeah. So that’s the key point because we’ve learned over the years that most screening tests are a closer call than we assumed. For too long, we have relegated messages about screening to sound bites simply convincing people that if you picked up a cancer when you didn’t have any symptoms that was necessarily a good thing. But we’re learning more and more about the harms and it’s a closer call than we often like to think.
So it’s important that people when they avail themselves of the option of screening that they know not only the potential benefits but what the harms are. That’s why organizations more and more are saying it’s a very personal decision. It should not be simply a sound bite, get screened or screening saves your life. It should be a discussion with the health professional about what you hope to gain by the screening, what are the benefits in absolute magnitude, and what are the harms in absolute magnitude, and is it right for me, and what is known about the strength of evidence.
Balintfy: How would you recap the important factors to remember regarding cancer screening?
Kramer: Well I think that the public should be aware of the tradeoffs and if they’re going to ask their doctor, they should come armed with a set of questions and that is what are the harms of the actual test, what are the benefits of having the test, how strong is the evidence, what is the magnitude of the benefits. For example not simply the relative benefits, it’s not very helpful to know that screening with a particular test reduces the risk of dying of the cancer by 20%. You have to know exactly in absolute terms what are the benefits. For example if there were a thousand people just like me and they were screened every year for ten years, how many of that 1000 would die of the disease if they had the test versus those that didn’t have the test. How many false positives would there be in that 1000, how many cases of over diagnosis would there be. And that is a quantum leap forward in developing an understanding of what the tradeoffs are. So I would say don’t simply go to your doctor and ask for a yes or no question, should I be screened or not.
Balintfy: Thanks to Dr. Barry Kramer at the NIH’s National Cancer Institute. For more information about cancer screening, and to get details about measuring the effectiveness of cancer screening tests and weighing the evidence from screening research studies, including the Physician Data Query, visit www.cancer.gov. Also, cancer screening and the science behind it is the topic of a recent Special Issues of the NCI Cancer Bulletin, which is also available at www.cancer.gov.
Balintfy: That’s it for this episode of NIH Research Radio. Please join us again on Friday, December 28th when our next edition will be available. I hope you’ll join me for what will be a special episode – an audio documentary featuring my extended voluntary participation in a clinical trial. In the meantime if you have any questions or comments about this program, or have story suggestions for a future episode, please let me know. Send an email to NIHRadio@mail.nih.gov. Also, please consider following NIH Radio via Twitter @NIHRadio, or on Facebook. Until next time, I'm your host, Joe Balintfy. Thanks for listening. And happy holidays from all of us here at NIH Radio.
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