The Best of Times, the Worst of Times
When during the day should you take your medication? Good question.By Emily AnthesPosted Thursday, Nov. 1, 2007, at 11:13 AM ET
It takes more than $800 million and 10 years to develop a new drug. Researchers perform study after study, testing a potential new medicine in cell cultures, animals, and humans. They determine whether it treats the right problem safely; should be taken orally, nasally, intravenously, or intramuscularly; and set minimum and maximum doses. But most drug trials ignore a question that increasingly seems crucial: When is the best time of day to take a given medication?
Modern drug development generally assumes that the body maintains a stable internal state. To that end, many prescription drugs are designed to be taken in equal amounts at regular intervals to keep a patient's drug levels steady. The problem is that a growing body of research suggests that our bodies are not constant. Instead, nearly every physiological process oscillates with our internal circadian rhythms. The body's temperature, immune function, and hormone levels all partly depend on whether it's night or day, or sometime in between. Meanwhile, many diseases also have daily rhythms, with symptoms more severe at certain times.
The body's sensitivity to time of day means that a drug proven safe to take in the morning may not be safe at night, or that a dose that works at 8 p.m. may be too small at 8 a.m. Some of the first—and still most compelling—evidence for these time-related differences came from Franz Halberg, widely considered to be the father of chronobiology. In a 1959 experiment that became a classic in the field, Halberg showed that it was easier for mice to survive a toxic dose of ethanol at one time of day than at another. Since then, time of day has proven to be an important factor in the safety and effectiveness of drugs for asthma, high blood pressure, and other conditions. These principles even apply to run-of-the-mill pills like aspirin, which does less damage to the stomach lining when taken in the evening than in the morning. (Conveniently, aspirin is also better at reducing blood pressure when taken before bed.)
Despite this evidence of variation, drug research is almost always done during daylight hours, when the humans leading the studies are awake and alert. And in the animal testing stage, it's almost always done with mice and rats, which are nocturnal—the middle of our day is the middle of their night. This can lead to gross misestimations of the effectiveness and toxicity of a drug intended for humans. "How much time, effort and money have been wasted in this way we shall probably never know," chronobiologist Josephine Arendt wrote in her 1998 overview of biological rhythms and medicine.
Things do get better, chronobiologically speaking, when drugs are eventually tested in humans, but only slightly so. The FDA requires three phases of clinical trials in humans before a new medicine can go on the market, but it does not require the testing of new compounds at multiple times of day. Instead, most clinical trials control for time of day. Which means that rather than assessing whether the effects of an experimental drug vary over the course of a day, the trials ensure that all patients take the drug in lockstep. When a drug is finally approved, the prescribing information issued by the FDA either contains no recommendation for what time of day patients should take it or directs patients to take it at whatever time was chosen for clinical trials, says Michael Smolensky, a chronobiologist at the University of Texas Health Sciences Center in Houston. And then, once the drug is on the market, a patient may decide to take a once-a-day drug at night, instead of in the morning, when it was tested—and experience side effects that neither the FDA nor the pharmaceutical companies anticipated.
Chronobiologists have tried—and failed—to change all of this. Several decades ago, Halberg led a delegation of scientists who met with FDA officials. "We recommended to the FDA commissioner that timing as well as dosing be considered in the administration of medications by a requirement in the package insert," Halberg wrote in a 2003 recounting of this effort. "The commissioner explicitly assured the delegation he would do something about it." But according to an assistant FDA commissioner who was a chronobiologist, Halberg says, after the delegation left, "the commissioner told the staff no more than to proceed with 'business as usual.' "
It doesn't help the chronobiologists' cause that they represent a small research niche in a mammoth industry. Unless drug companies think there's serious money at stake, they're unlikely to poke around in the lab just to see whether a new medication has time-related effects. Drug trials that consider chronobiology would be more complex and require more patients than the status quo. What's more, most medical professionals simply aren't aware of the extent to which the body's rhythms influence its response to medicine, Smolensky says. "There is no active conspiracy against chronomedicine," he writes in his book The Body Clock Guide to Better Health. "The biggest barrier is simply inertia."
Yet there are relatively easy ways to address the issue. Research has shown that nocturnal animals can reverse their usual biological rhythms if the rooms in which they are housed are kept relatively dark during the day and lighter at night. Drug studies should, at the very least, use animals on this adjusted schedule. Better yet, they could use two groups of rodents, a standard nocturnal set and another one on a reverse schedule. That way, scientists would be able to notice early on whether time affects how a drug works.
When it comes to human testing, the FDA could mandate small, early stage clinical trials with different groups of patients taking a drug at least three different times of day. If a certain drug turns out to have no time-related differences, we'll be reassured that it's safe to take anytime. Nobody knows precisely how many drugs exhibit time-related effects, but the number isn't tiny. Many different kinds of medications behave this way, and how important the variations are depends on factors like the seriousness of the illness being treated and the side effects of the medication.
Yes, these changes will require drug trials that are larger and more costly. But the return on investment could be huge in some areas. For instance, doctors have already successfully begun integrating circadian rhythms into cancer treatment. Chemotherapy causes its famously debilitating side effects because the drugs used are highly toxic to healthy as well as cancerous cells. It turns out, however, that based on the circadian rhythm, doctors can administer chemo at a time when malignant cells are more susceptible to the drugs than normal ones are. Such carefully timed treatment has been shown to help patients tolerate higher doses of chemo and survive longer. Cancer has become one of chronomedicine's biggest success stories. When will we hear about the next one? The clock is ticking.
Sunday, November 04, 2007
THE SCARY SIDE OF HEALTH TESTING
The proliferation of new health screens -- many not covered by insurance -- that try to detect disaster early in patients don't really work that well, says Forbes Magazine.
Many of the scans yield false-positive results, which lead to unnecessary (and risky) treatments. Even recommended tests yield a scary number of false readings. Take mammograms, an often promoted routine exam. According to research compiled by the U.S. Agency for Healthcare Research and Quality:
The percentage of false-positive readings is between 7 percent and 8 percent for women aged 40 to 59 who took the test.
That figure drops to around 4 percent for women 60 to 79, mainly because the chances of getting breast cancer rise the older women get.
If every woman between 40 and 59 in the United States had a mammogram, a few million would be fretting unnecessarily over a wrong result.
Perhaps the most dubious of all the tests are total body scans, says Forbes. According to recent research by G. Scott Gazelle, director of Massachusetts General Hospital's Institute for Technology Assessment:
Some 90.8 percent of patients who had a full-body scan got a least one positive finding that led to additional testing.
However, only 2 percent of those actually had a disease.
Worse, these tests cost between several hundred and several thousand dollars -- and most insurance companies won't cover them.
Not all tests are unreliable. The United States Preventive Services Task Force says some commonly recommended tests including Pap smears, high blood-pressure tests, colorectal cancer screens and something called the Factor V Leiden test, which checks a person's predisposition to blood clots, deliver sufficient preventive value -- net of false readings and the risks association with doing further procedures based on them.
Source: Maureen Farrell, "The Scary Side Of Health Testing," Forbes Magazine, October 30, 2007.
The proliferation of new health screens -- many not covered by insurance -- that try to detect disaster early in patients don't really work that well, says Forbes Magazine.
Many of the scans yield false-positive results, which lead to unnecessary (and risky) treatments. Even recommended tests yield a scary number of false readings. Take mammograms, an often promoted routine exam. According to research compiled by the U.S. Agency for Healthcare Research and Quality:
The percentage of false-positive readings is between 7 percent and 8 percent for women aged 40 to 59 who took the test.
That figure drops to around 4 percent for women 60 to 79, mainly because the chances of getting breast cancer rise the older women get.
If every woman between 40 and 59 in the United States had a mammogram, a few million would be fretting unnecessarily over a wrong result.
Perhaps the most dubious of all the tests are total body scans, says Forbes. According to recent research by G. Scott Gazelle, director of Massachusetts General Hospital's Institute for Technology Assessment:
Some 90.8 percent of patients who had a full-body scan got a least one positive finding that led to additional testing.
However, only 2 percent of those actually had a disease.
Worse, these tests cost between several hundred and several thousand dollars -- and most insurance companies won't cover them.
Not all tests are unreliable. The United States Preventive Services Task Force says some commonly recommended tests including Pap smears, high blood-pressure tests, colorectal cancer screens and something called the Factor V Leiden test, which checks a person's predisposition to blood clots, deliver sufficient preventive value -- net of false readings and the risks association with doing further procedures based on them.
Source: Maureen Farrell, "The Scary Side Of Health Testing," Forbes Magazine, October 30, 2007.
Cell Phones in the ED
OK, I couldn’t take it any more. The rant of the day is cell phones, ladies and gentlemen.
It is a pet peeve of mine when I am in a room with a patient and someone answers their cell phone. Don’t get me wrong, my phone is often on vibrate if I am in a meeting. Unless someone knows the secret code for emergency, I’ll wait until I am out of the meeting or will sometimes look to see who is calling and then put my phone back in the holster. Ed McMahon never seems to call me when I want him to. I rarely if ever answer my cell phone when in the presence of someone else and if I do so, I excuse myself and leave their presence.More than 90% of the people in emergency rooms just pick up their cell phone and begin blabbing as if nothing is out of the ordinary. “Yeah, mom’s blood pressure is 70/nothing and the doctor is about to stick a funny looking tube down her throat. Who are you going to the dance with next winter?”There was a doctor I worked with a long time ago who used to carry her cell phone around with her when she saw patients. The nurses told me that one time she got into a shouting match with her boyfriend on her cell phone in a patient’s room … during a code.
Our hospital has signs up all over the place stating that cell phones must be turned off. Even though they probably aren’t accurate, we quote the studies stating that cell phones can interfere with medical equipment. A specific case was reported by the FDA, but I’m a little leery about quoting anything the FDA says right about now.
Despite the signs, I have had family members talk so loud that I can’t even obtain a history from the patient. At first I stop talking and stare at them, but some people don’t get the hint. They just keep chatting away. Then, depending upon my mood, I will either ask the family member to leave the room or, in a louder voice, I will tell the patient that I cannot understand what they are saying because their family member is talking too loud … on their cellphone … which is supposed to be turned off in the emergency department.
Some family members have pulled a John Madden on me. When I examine the patient, they give the person on the other end of the line a play-by-play of everything I am doing. “He is listening to her lungs now. He is making a face. Wonder what that means. Oops, probably nothing. He just itched his nose. Now he is listening to her heart. Mom had problems with her heart as a kid, you know. Now he is pressing on her stomach. Ooooh, she just moaned in pain. That had ta’ hurt. I wonder if he is going to give her any pain medicine…” I have always wanted to end that type of conversation something like “Now the doctor is walking toward me. He is grabbing the phone out of my hands. He is throwing it against the … [Disconnect].” Kind of like this.
Patients can be just as bad as the family members. I understand that sometimes people have to wait a long time and they talk on the phone to pass the time. But if it is busy, when I finally do walk in the room, I would hope that the patient would want to talk to me instead of someone they’re going to see an hour later if they get discharged. Some times I guess people just find me boring.
A few days ago, there was a young guy who was brought in by ambulance for chest pain (yes, he got his EKG on arrival). I walked in the room about 30 minutes after he arrived and he had his cell phone to one ear and the hospital phone to his other ear. He was alternating talking into one phone and then the other. I walked in and told him “Sorry about the wait, I’m Dr. WhiteCoat. What can I do to help you?” He just kept talking into his cell phone as if I was not there. I waited about five more seconds for him to finish his conversation and it appeared that he had no intent of doing so. I then told him in a loud voice “I will be back when you are off of your phone.”I went to see a couple of other patients, admitted someone, and then came back in the room. He was still on his cell phone, but as soon as he saw me walk through the door, he said “gotta go” and hung up the phone. He ended up being an OK guy, and, after reviewing his old records and normal stress test, his chest pain appeared to be from his stomach and not his heart.I was talking with our lab technician while the patient was over and the x-ray department. I had mentioned the issue I had with the patient on a cell phone. We commiserated over some peoples’ lack of cell phone etiquette.Shortly afterwards, the patient was wheeled back into the room by the x-ray technician. The lab technician went into the room literally 30 seconds later to draw blood. He was in there for a few minutes and then came out with a smile on his face.“When I went in the room, he was already on his cell phone. As soon as I opened the door, he hung up the phone. Then when he saw it was me, he opened the phone back up and made a call. He told me ‘I thought you were that doctor again. I didn’t want to him to make me wait another hour before he came in and gave me the results of my tests.’”
If anyone ever invents a portable device to make someone else’s cell phone disconnect a call remotely, I’ll be the first in line to purchase it. Price is no object.
OK, I couldn’t take it any more. The rant of the day is cell phones, ladies and gentlemen.
It is a pet peeve of mine when I am in a room with a patient and someone answers their cell phone. Don’t get me wrong, my phone is often on vibrate if I am in a meeting. Unless someone knows the secret code for emergency, I’ll wait until I am out of the meeting or will sometimes look to see who is calling and then put my phone back in the holster. Ed McMahon never seems to call me when I want him to. I rarely if ever answer my cell phone when in the presence of someone else and if I do so, I excuse myself and leave their presence.More than 90% of the people in emergency rooms just pick up their cell phone and begin blabbing as if nothing is out of the ordinary. “Yeah, mom’s blood pressure is 70/nothing and the doctor is about to stick a funny looking tube down her throat. Who are you going to the dance with next winter?”There was a doctor I worked with a long time ago who used to carry her cell phone around with her when she saw patients. The nurses told me that one time she got into a shouting match with her boyfriend on her cell phone in a patient’s room … during a code.
Our hospital has signs up all over the place stating that cell phones must be turned off. Even though they probably aren’t accurate, we quote the studies stating that cell phones can interfere with medical equipment. A specific case was reported by the FDA, but I’m a little leery about quoting anything the FDA says right about now.
Despite the signs, I have had family members talk so loud that I can’t even obtain a history from the patient. At first I stop talking and stare at them, but some people don’t get the hint. They just keep chatting away. Then, depending upon my mood, I will either ask the family member to leave the room or, in a louder voice, I will tell the patient that I cannot understand what they are saying because their family member is talking too loud … on their cellphone … which is supposed to be turned off in the emergency department.
Some family members have pulled a John Madden on me. When I examine the patient, they give the person on the other end of the line a play-by-play of everything I am doing. “He is listening to her lungs now. He is making a face. Wonder what that means. Oops, probably nothing. He just itched his nose. Now he is listening to her heart. Mom had problems with her heart as a kid, you know. Now he is pressing on her stomach. Ooooh, she just moaned in pain. That had ta’ hurt. I wonder if he is going to give her any pain medicine…” I have always wanted to end that type of conversation something like “Now the doctor is walking toward me. He is grabbing the phone out of my hands. He is throwing it against the … [Disconnect].” Kind of like this.
Patients can be just as bad as the family members. I understand that sometimes people have to wait a long time and they talk on the phone to pass the time. But if it is busy, when I finally do walk in the room, I would hope that the patient would want to talk to me instead of someone they’re going to see an hour later if they get discharged. Some times I guess people just find me boring.
A few days ago, there was a young guy who was brought in by ambulance for chest pain (yes, he got his EKG on arrival). I walked in the room about 30 minutes after he arrived and he had his cell phone to one ear and the hospital phone to his other ear. He was alternating talking into one phone and then the other. I walked in and told him “Sorry about the wait, I’m Dr. WhiteCoat. What can I do to help you?” He just kept talking into his cell phone as if I was not there. I waited about five more seconds for him to finish his conversation and it appeared that he had no intent of doing so. I then told him in a loud voice “I will be back when you are off of your phone.”I went to see a couple of other patients, admitted someone, and then came back in the room. He was still on his cell phone, but as soon as he saw me walk through the door, he said “gotta go” and hung up the phone. He ended up being an OK guy, and, after reviewing his old records and normal stress test, his chest pain appeared to be from his stomach and not his heart.I was talking with our lab technician while the patient was over and the x-ray department. I had mentioned the issue I had with the patient on a cell phone. We commiserated over some peoples’ lack of cell phone etiquette.Shortly afterwards, the patient was wheeled back into the room by the x-ray technician. The lab technician went into the room literally 30 seconds later to draw blood. He was in there for a few minutes and then came out with a smile on his face.“When I went in the room, he was already on his cell phone. As soon as I opened the door, he hung up the phone. Then when he saw it was me, he opened the phone back up and made a call. He told me ‘I thought you were that doctor again. I didn’t want to him to make me wait another hour before he came in and gave me the results of my tests.’”
If anyone ever invents a portable device to make someone else’s cell phone disconnect a call remotely, I’ll be the first in line to purchase it. Price is no object.
A Wikipedia wizard and blogger
Bertalan Mesko combines being an editor and administrator of Wikipedia with medical student studies, as Tiago Villanueva found out
How did you get involved with Wikipedia?
In 2005 I started editing the Hungarian Wikipedia and later became an administrator. In October 2006 I became an administrator in the English Wikipedia. Now I maintain the medicine portal, medicine wikiproject, and medical collaboration of the week, and I'm the creator and maintainer of the medical genetics wikiproject.
How do you think Wikipedia will develop?
Wikipedia has a great future. The most common criticism is that it can be edited by anyone. The most important task for Wikipedia editors is to reference statements, numbers, and dates. I won't consider an article reliable if it lacks appropriate references, even if it is written by a professor.
Why blog?
To be honest, in the first month it was just for fun. Now it feels more like work, but I still love it. Web 2.0 will play an important role in the future of medicine. Hundreds of web tools are created for physicians and scientists, and I try to present these to them. I've made several blogterviews (interviews by email)-for example, with Michael Breus, the American sleep doctor, and Juan Magdaraog, a leading clinical geneticist who is blogging about his fight with Pompe disease. Because of my blog and Wikipedia work, I've been mentioned in Nature Medicine and Medscape.
What are your career plans after graduation?
Specialist training in the United States or in the United Kingdom. I plan to pledge my life to personalised genetics and find a way to tell physicians from all medical specialties about these web 2.0 tools created for them.
Is genetics given priority at medical school?
In my opinion, no. I can tell you only how Hungarian medical education works. To become a physician in Hungary, you have to finish 12 semesters. Human genetics takes one semester and clinical genetics takes another. Genetics has a role in nearly all medical specialties. That's why I think genetics should form a much bigger component of medical studies.
How is the web relevant to geneticists?
Being up to date is key. Genetics is typically a field where you have to read dozens of articles every day. Then you need to be open to new developments. Many aspects of genetics are uncharted, and I'm totally convinced that some breakthroughs in the near future will change the way we see genetics today. A modern geneticist must be proficient in Web 2.0: genetic searches, databases, scientific community sites (like biowizard.com), really simple syndication (RSS), and podcasts. In a dynamically changing field like genetics, web has a key part in the work.
What advances in genetics do you foresee in the next decade?
I love science fiction, but in medicine I'm realistic. I'm expecting the creation of a universal prenatal and newborn screening system. It's always easier to prevent than to treat. When I was making the blogterview with the patient with Pompe disease, I realised that there was a lag of two to three years between the appearance of the first symptoms and the diagnosis. I dream about a future where people often use genetic counselling, and where most of the known and common genetic diseases are screened. As a dreamer, I'd like to know the number of human genes, the role of all the RNA subtypes, and the hereditary details of multifactorial diseases. Personalised genetics will rule the next decade for sure.
Further information
Medgadget (www.medgadget.com/archives/2007/01/2006_medical_we.html)
Technorati (http://technorati.com/about)-Technorati is currently tracking 74.3 million blogs
iHealthBeat (www.ihealthbeat.org/index.cfm?action=dspItem&itemID=129182)
Fact file
Name-Bertalan Mesko
Position-Medical student, University of Debrecen, Hungary
Biography-Administrator and coordinator of the medical projects of the English language Wikipedia. His medical blog, Scienceroll (http://scienceroll.com), received a special mention in Medgadget's weblog awards in 2007
Bertalan Mesko combines being an editor and administrator of Wikipedia with medical student studies, as Tiago Villanueva found out
How did you get involved with Wikipedia?
In 2005 I started editing the Hungarian Wikipedia and later became an administrator. In October 2006 I became an administrator in the English Wikipedia. Now I maintain the medicine portal, medicine wikiproject, and medical collaboration of the week, and I'm the creator and maintainer of the medical genetics wikiproject.
How do you think Wikipedia will develop?
Wikipedia has a great future. The most common criticism is that it can be edited by anyone. The most important task for Wikipedia editors is to reference statements, numbers, and dates. I won't consider an article reliable if it lacks appropriate references, even if it is written by a professor.
Why blog?
To be honest, in the first month it was just for fun. Now it feels more like work, but I still love it. Web 2.0 will play an important role in the future of medicine. Hundreds of web tools are created for physicians and scientists, and I try to present these to them. I've made several blogterviews (interviews by email)-for example, with Michael Breus, the American sleep doctor, and Juan Magdaraog, a leading clinical geneticist who is blogging about his fight with Pompe disease. Because of my blog and Wikipedia work, I've been mentioned in Nature Medicine and Medscape.
What are your career plans after graduation?
Specialist training in the United States or in the United Kingdom. I plan to pledge my life to personalised genetics and find a way to tell physicians from all medical specialties about these web 2.0 tools created for them.
Is genetics given priority at medical school?
In my opinion, no. I can tell you only how Hungarian medical education works. To become a physician in Hungary, you have to finish 12 semesters. Human genetics takes one semester and clinical genetics takes another. Genetics has a role in nearly all medical specialties. That's why I think genetics should form a much bigger component of medical studies.
How is the web relevant to geneticists?
Being up to date is key. Genetics is typically a field where you have to read dozens of articles every day. Then you need to be open to new developments. Many aspects of genetics are uncharted, and I'm totally convinced that some breakthroughs in the near future will change the way we see genetics today. A modern geneticist must be proficient in Web 2.0: genetic searches, databases, scientific community sites (like biowizard.com), really simple syndication (RSS), and podcasts. In a dynamically changing field like genetics, web has a key part in the work.
What advances in genetics do you foresee in the next decade?
I love science fiction, but in medicine I'm realistic. I'm expecting the creation of a universal prenatal and newborn screening system. It's always easier to prevent than to treat. When I was making the blogterview with the patient with Pompe disease, I realised that there was a lag of two to three years between the appearance of the first symptoms and the diagnosis. I dream about a future where people often use genetic counselling, and where most of the known and common genetic diseases are screened. As a dreamer, I'd like to know the number of human genes, the role of all the RNA subtypes, and the hereditary details of multifactorial diseases. Personalised genetics will rule the next decade for sure.
Further information
Medgadget (www.medgadget.com/archives/2007/01/2006_medical_we.html)
Technorati (http://technorati.com/about)-Technorati is currently tracking 74.3 million blogs
iHealthBeat (www.ihealthbeat.org/index.cfm?action=dspItem&itemID=129182)
Fact file
Name-Bertalan Mesko
Position-Medical student, University of Debrecen, Hungary
Biography-Administrator and coordinator of the medical projects of the English language Wikipedia. His medical blog, Scienceroll (http://scienceroll.com), received a special mention in Medgadget's weblog awards in 2007
Saturday, November 03, 2007
Elderly with high blood pressure less likely to get lifestyle modification advice from doctors
CHAPEL HILL – People older than 60 with high blood pressure are less likely than other groups of patients to receive advice from their doctors about lifestyle modifications that can help lower their blood pressure, a study by UNC researchers concludes.
In addition, hypertension (high blood pressure) patients who are not taking antihypertensive medication and patients who are not overweight or obese are less likely to receive lifestyle modification advice than groups such as hypertension patients aged 18 to 39, those who are overweight or obese and those taking antihypertensive medication, said Anthony J. Viera, M.D., M.P.H., the study’s lead author.
“Our study found that most people who have been diagnosed with high blood pressure say they remember receiving at least some advice from their doctors about lifestyle modifications – such as eating healthier, exercising more and reducing both salt and alcohol intake – that can help lower their blood pressure,” Viera said.
“However, the most important finding of the study is who is not getting that advice,” Viera said. “Lifestyle modification advice should always be the doctor’s first step in treating a patient with high blood pressure, and this advice should not be abandoned at any point, in any group of hypertension patients.”
The study is published in the November 2007 issue of The Journal of Clinical Hypertension. Viera, an assistant professor in the Department of Family Medicine, was the principal investigator. His UNC co-authors are Abhijit V. Kshirsagar, M.D., M.P.H., and Alan L. Hinderliter, M.D.
For their study, Viera and colleagues analyzed data collected by the Centers for Disease Control and Prevention in a national survey of 28,457 adults with high blood pressure. They found that 90.3 percent of those surveyed reported receiving some type of lifestyle modification advice from their doctors. Of these, 74.6 percent reported receiving exercise advice, 69.3 percent were told to reduce salt intake, 61.9 percent were told to change their eating habits and 43.5 percent said they were advised to reduce alcohol intake.
But disparities emerged when the researchers examined the survey results for particular types of advice received by particular groups of patients. For example, 53.7 percent of those aged 60 or older reported receiving eating habit advice, compared to 71.2 percent of those aged 40-59 and 64.9 percent of those aged 18-39. Similarly, 35.1 percent of those 60 or older reported receiving advice to reduce alcohol intake, compared to 48.9 percent of those aged 40-59 and 43.4 percent of those aged 18-39.
“It is possible that health care providers may put aside or even abandon the notion of giving LSM advice to older patients, perhaps feeling that their hypertension mandates the use of medication,” the researchers wrote. “Even for individuals on medication, however, LSM should remain an important part of hypertension management; it can help reduce the need for higher doses of medication or multiple antihypertensive agents.”
When the survey responses were sorted according to body weight, 45.5 percent of those who were underweight or at a healthy weight reported receiving eating habit advice, compared to 59.5 percent of those who were overweight and 75 percent of those were were obese. When the results were sorted according to medication use, 63.2 percent those who were taking antihypertensive medication reported receiving eating habit advice, compared to 56.9 percent of those not taking medication.
A greater disparity emerged in the medication group when exercise advice was examined. Of those taking medication, 82.6 percent reported receiving exercise advice, compared to 65.9 of those not taking
CHAPEL HILL – People older than 60 with high blood pressure are less likely than other groups of patients to receive advice from their doctors about lifestyle modifications that can help lower their blood pressure, a study by UNC researchers concludes.
In addition, hypertension (high blood pressure) patients who are not taking antihypertensive medication and patients who are not overweight or obese are less likely to receive lifestyle modification advice than groups such as hypertension patients aged 18 to 39, those who are overweight or obese and those taking antihypertensive medication, said Anthony J. Viera, M.D., M.P.H., the study’s lead author.
“Our study found that most people who have been diagnosed with high blood pressure say they remember receiving at least some advice from their doctors about lifestyle modifications – such as eating healthier, exercising more and reducing both salt and alcohol intake – that can help lower their blood pressure,” Viera said.
“However, the most important finding of the study is who is not getting that advice,” Viera said. “Lifestyle modification advice should always be the doctor’s first step in treating a patient with high blood pressure, and this advice should not be abandoned at any point, in any group of hypertension patients.”
The study is published in the November 2007 issue of The Journal of Clinical Hypertension. Viera, an assistant professor in the Department of Family Medicine, was the principal investigator. His UNC co-authors are Abhijit V. Kshirsagar, M.D., M.P.H., and Alan L. Hinderliter, M.D.
For their study, Viera and colleagues analyzed data collected by the Centers for Disease Control and Prevention in a national survey of 28,457 adults with high blood pressure. They found that 90.3 percent of those surveyed reported receiving some type of lifestyle modification advice from their doctors. Of these, 74.6 percent reported receiving exercise advice, 69.3 percent were told to reduce salt intake, 61.9 percent were told to change their eating habits and 43.5 percent said they were advised to reduce alcohol intake.
But disparities emerged when the researchers examined the survey results for particular types of advice received by particular groups of patients. For example, 53.7 percent of those aged 60 or older reported receiving eating habit advice, compared to 71.2 percent of those aged 40-59 and 64.9 percent of those aged 18-39. Similarly, 35.1 percent of those 60 or older reported receiving advice to reduce alcohol intake, compared to 48.9 percent of those aged 40-59 and 43.4 percent of those aged 18-39.
“It is possible that health care providers may put aside or even abandon the notion of giving LSM advice to older patients, perhaps feeling that their hypertension mandates the use of medication,” the researchers wrote. “Even for individuals on medication, however, LSM should remain an important part of hypertension management; it can help reduce the need for higher doses of medication or multiple antihypertensive agents.”
When the survey responses were sorted according to body weight, 45.5 percent of those who were underweight or at a healthy weight reported receiving eating habit advice, compared to 59.5 percent of those who were overweight and 75 percent of those were were obese. When the results were sorted according to medication use, 63.2 percent those who were taking antihypertensive medication reported receiving eating habit advice, compared to 56.9 percent of those not taking medication.
A greater disparity emerged in the medication group when exercise advice was examined. Of those taking medication, 82.6 percent reported receiving exercise advice, compared to 65.9 of those not taking
Nanotechnology-Based Strategy Aims at Noninvasive Cancer Therapy
HOUSTON, Nov. 2 -- Carbon nanotubes embedded in tumors and then heated externally by radiofrequency energy achieved total tumor necrosis in preclinical studies, investigators here reported.
Action Points
Explain to interested patients that research involving microscopic technology has shown promise in animals as a noninvasive approach to treating cancer.
Point out that the approach has not been tested in humans and might not be for several years.
The heated nanotubes initially destroyed cancer cells in vitro and then obliterated tumors in a rabbit model of liver cancer, Steven A. Curley, M.D., of the University of Texas M. D. Anderson Cancer Center, and colleagues, reported online in advance of the December issue of Cancer.
The approach suggested a potential noninvasive means to treat tumors virtually anywhere in the body, said the investigators. The treatment damaged some healthy tissue adjacent to tumors, but investigators found encouragement in the overall results of the study.
"These are promising, even exciting, preclinical results in this liver cancer model," said Dr. Curley. "Our next step is to look at ways to more precisely target the nanotubes so they attach to, and are taken up by, cancer cells while avoiding normal tissue."
Dr. Curley estimated that clinical studies are at least three or four years away.
Radiofrequency ablation of tumors, as currently practiced, has several drawbacks--the need to insert needles directly into tumors; incomplete tumor destruction in as many as 40% of cases; nonspecific treatment resulting in damage to healthy tissue; and complications of thermal injury in 10% of patients. As a consequence, the therapy is used for only a few malignancies, including liver, kidney, breast, lung, and bone.
Radiofrequency energy fields have excellent tissue penetration, the authors noted. Theoretically, the process could be used for noninvasive treatment of tumors located anywhere in the body.
Single-walled carbon nanotubes also have considerable potential in cancer therapy, the authors continued. The nanotubes can be used to deliver a variety of diagnostic and therapeutic agents.
"Given the unique electrical and chemical properties of [single-walled carbon nanotubes], we hypothesized that exposure to a focused external radiofrequency field would lead to significant heat release by the [nanotubes] allowing them to serve directly as an anticancer agent," they said.
The initial studies involved human liver cancer cells, to which the water-soluble nanotubes were added. After incorporation of the nanotubes, the cells were exposed for one to two minutes to an 800-watt external radiofrequency field.
The radiofrequency energy resulted in efficient heating of the aqueous suspensions of nanotubes and concentration-dependent destruction in vitro of the human cancer cells.
In the second phase of investigation, the researchers injected the nanotubes directly into tumors. That was followed immediately by external RF field treatment. At 48 hours all of the nanotube-containing tumors demonstrated complete necrosis. In contrast, control tumors with nanotube or radiofrequency exposure (but not both) remained viable.
Dr. Curley said targeting nanotubes to cancer cells is the major obstacle in advancing the therapy. Investigators are examining the ability of monoclonal antibodies, peptides, and other potential delivery vehicles to target the nanotubes more specifically.
The authors reported no disclosures. The study was supported by the American Association for Cancer Research, the National Aeronautics and Space Administration, the National Science Foundation, and the Fulbright Foundation.Primary source: CancerSource reference: Gannon CJ, et al. "Carbon nanotube-enhanced thermal destruction of cancer cells in a non-invasive radiofrequency field." Cancer 2007;110:epub.
HOUSTON, Nov. 2 -- Carbon nanotubes embedded in tumors and then heated externally by radiofrequency energy achieved total tumor necrosis in preclinical studies, investigators here reported.
Action Points
Explain to interested patients that research involving microscopic technology has shown promise in animals as a noninvasive approach to treating cancer.
Point out that the approach has not been tested in humans and might not be for several years.
The heated nanotubes initially destroyed cancer cells in vitro and then obliterated tumors in a rabbit model of liver cancer, Steven A. Curley, M.D., of the University of Texas M. D. Anderson Cancer Center, and colleagues, reported online in advance of the December issue of Cancer.
The approach suggested a potential noninvasive means to treat tumors virtually anywhere in the body, said the investigators. The treatment damaged some healthy tissue adjacent to tumors, but investigators found encouragement in the overall results of the study.
"These are promising, even exciting, preclinical results in this liver cancer model," said Dr. Curley. "Our next step is to look at ways to more precisely target the nanotubes so they attach to, and are taken up by, cancer cells while avoiding normal tissue."
Dr. Curley estimated that clinical studies are at least three or four years away.
Radiofrequency ablation of tumors, as currently practiced, has several drawbacks--the need to insert needles directly into tumors; incomplete tumor destruction in as many as 40% of cases; nonspecific treatment resulting in damage to healthy tissue; and complications of thermal injury in 10% of patients. As a consequence, the therapy is used for only a few malignancies, including liver, kidney, breast, lung, and bone.
Radiofrequency energy fields have excellent tissue penetration, the authors noted. Theoretically, the process could be used for noninvasive treatment of tumors located anywhere in the body.
Single-walled carbon nanotubes also have considerable potential in cancer therapy, the authors continued. The nanotubes can be used to deliver a variety of diagnostic and therapeutic agents.
"Given the unique electrical and chemical properties of [single-walled carbon nanotubes], we hypothesized that exposure to a focused external radiofrequency field would lead to significant heat release by the [nanotubes] allowing them to serve directly as an anticancer agent," they said.
The initial studies involved human liver cancer cells, to which the water-soluble nanotubes were added. After incorporation of the nanotubes, the cells were exposed for one to two minutes to an 800-watt external radiofrequency field.
The radiofrequency energy resulted in efficient heating of the aqueous suspensions of nanotubes and concentration-dependent destruction in vitro of the human cancer cells.
In the second phase of investigation, the researchers injected the nanotubes directly into tumors. That was followed immediately by external RF field treatment. At 48 hours all of the nanotube-containing tumors demonstrated complete necrosis. In contrast, control tumors with nanotube or radiofrequency exposure (but not both) remained viable.
Dr. Curley said targeting nanotubes to cancer cells is the major obstacle in advancing the therapy. Investigators are examining the ability of monoclonal antibodies, peptides, and other potential delivery vehicles to target the nanotubes more specifically.
The authors reported no disclosures. The study was supported by the American Association for Cancer Research, the National Aeronautics and Space Administration, the National Science Foundation, and the Fulbright Foundation.Primary source: CancerSource reference: Gannon CJ, et al. "Carbon nanotube-enhanced thermal destruction of cancer cells in a non-invasive radiofrequency field." Cancer 2007;110:epub.
The need for speed: Two new studies on stroke
Majority of patients still get to the hospital too late for best treatment, so more public education is needed ?including a promising program in middle schools
ANN ARBOR, Mich. ¡ª Every 45 seconds, an American suffers a stroke. Every minute one of those individuals goes without treatment, more brain cells die. And every hour that passes before victims get to the hospital, the less likely they are to be eligible for the most effective treatment.
But despite all this, 69 percent of stroke victims don¡¯t reach the hospital in the first three hours after their stroke symptoms begin, according to a new study led by the University of Michigan Stroke Program and published in the journal Stroke.
That delay keeps many patients from receiving tPA, the only approved treatment for stroke caused by blood clots in the brain. If it¡¯s given intravenously within the first three hours of the start of a stroke, or injected directly into the brain within six hours, tPA can break up clots and stop or slow the damage caused by strokes.
But in the new study, only 44 percent of patients experiencing full-blown clot-based strokes got to the hospital even within six hours of the start of their symptoms ¨C and 36 percent didn¡¯t get there until more than 12 hours had passed. The study was conducted between 2000 and 2005 in Corpus Christi, Texas ¨C an area with no major university hospitals, making it a ¡°real world¡± snapshot of stroke care in America.
The researchers say their findings confirm previous studies and underscore the importance of public education efforts to help everyone understand that when a stroke strikes, they should call 911 right away.
In fact, in a second paper published in Stroke, a U-M-led team describes the positive effects of an education effort aimed at middle-schoolers in the same area of Texas. After three years in which some children received four hours a year of stroke-related instruction and some didn¡¯t, a test showed the first group of children was much more likely to know how to recognize a stroke and to indicate they would call 911 if they witnessed someone having a stroke.
¡°Efforts to speed up patients¡¯ arrival at the hospital are absolutely crucial. We have very effective treatments, we just need to get patients to the hospital as fast as possible,¡± says Lewis Morgenstern, M.D., senior author of the hospital study and first author of the school study. ¡°Our first paper really speaks to the need to educate and motivate the public to call 911 for stroke, while the second shows one means to accomplish that goal.¡±
Both studies are from a community-based research effort funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. Researchers from the University of Texas at Houston and Eastern Michigan University are also involved.
The hospital study included 2,347 patients with ischemic (clot-based) strokes who reported to hospitals in the study area between January 2000 and June 2005. The average age was 71 years, and just over half were women. U-M stroke neurologist Jennifer Majersik, M.D., led the analysis.
The researchers reviewed medical records in detail, looking for information on what time each patient was last known to be without symptoms, and what time they reached the hospital. In some cases, when an exact time for the start of the symptoms was not known, the researchers used an estimate. They broke the patients up into groups by the time to presentation (arrival) at the hospital: less than three hours, three to six hours, six to 12 hours, and more than 12 hours.
The researchers also assessed how severe the patients¡¯ strokes were, and looked for differences in the time to hospital presentation for each severity group. The patients with the most severe strokes made it to the hospital in the fastest time, with nearly half of them making it in less than three hours. In contrast, only 28 percent of patients with the mildest level of stroke made it in that time. The study did not include patients who suffered transient ischemic attacks, also referred to as ¡°mini strokes.¡± Nor did it include patients with ¡°bleeding strokes¡± such as intracranial hemorrhages.
No matter what kind of stroke or mini-strokes patients have, the best course of action in all cases is to call 911, so that an ambulance or other emergency medical team can arrive and transport the patient to the hospital. Driving to the hospital oneself, or being driven by a friend or loved one, is less ideal because of delays that can occur en route or upon arrival at the hospital.
Even at major hospitals with dedicated 24-hour stroke teams, such as U-M, it can take an hour or more to use diagnostic tests to assess what type of stroke a patient is having and to start tPA treatment. At smaller hospitals, it can be more than an hour ¨C and intra-arterial tPA, which can be given up to six hours after the start of a stroke, may not be available.
So, a person experiencing a stroke really needs to get to a hospital within two hours of the start of a stroke to have the best chance of receiving tPA, says Morgenstern, who is a professor of neurology, emergency medicine and neurosurgery at the U-M Medical School and a member of the U-M Cardiovascular Center.
This kind of information, and the scientific reasons behind it, is what the public needs to hear from childhood on. That¡¯s why Morgenstern and his colleagues, including Kathleen Conley, Ph.D., of the School of Health Promotion and Human Performance at EMU, developed the ¡°Kids Identifying and Defeating Stroke¡± program, called KIDS for short.
The KIDS project involved middle schoolers in the Corpus Christi district, who were tested on three things: their knowledge of what a stroke is, their ability to identify stroke symptoms and their knowledge of what to do if someone around them appeared to be having a stroke.
One group was tested in both sixth and eighth grades but did not receive any specific in-school training about stroke. The other group was tested in sixth grade before receiving four hours of stroke education each year for three years as part of their school curriculum. They were tested again at the end of the three years. Parents of both groups were also approached for testing.
The students who had had the in-school training tested better in eighth grade than those who had not, with the most dramatic increase in correct answers seen in the part of the test that assessed whether students knew that calling 911 was the best option for responding to a stroke.
The students were also given homework assignments to share the stroke information with their parents or other adults, and assess their understanding of stroke. However, not enough of these assignments were completed to allow for a valid analysis.
Majority of patients still get to the hospital too late for best treatment, so more public education is needed ?including a promising program in middle schools
ANN ARBOR, Mich. ¡ª Every 45 seconds, an American suffers a stroke. Every minute one of those individuals goes without treatment, more brain cells die. And every hour that passes before victims get to the hospital, the less likely they are to be eligible for the most effective treatment.
But despite all this, 69 percent of stroke victims don¡¯t reach the hospital in the first three hours after their stroke symptoms begin, according to a new study led by the University of Michigan Stroke Program and published in the journal Stroke.
That delay keeps many patients from receiving tPA, the only approved treatment for stroke caused by blood clots in the brain. If it¡¯s given intravenously within the first three hours of the start of a stroke, or injected directly into the brain within six hours, tPA can break up clots and stop or slow the damage caused by strokes.
But in the new study, only 44 percent of patients experiencing full-blown clot-based strokes got to the hospital even within six hours of the start of their symptoms ¨C and 36 percent didn¡¯t get there until more than 12 hours had passed. The study was conducted between 2000 and 2005 in Corpus Christi, Texas ¨C an area with no major university hospitals, making it a ¡°real world¡± snapshot of stroke care in America.
The researchers say their findings confirm previous studies and underscore the importance of public education efforts to help everyone understand that when a stroke strikes, they should call 911 right away.
In fact, in a second paper published in Stroke, a U-M-led team describes the positive effects of an education effort aimed at middle-schoolers in the same area of Texas. After three years in which some children received four hours a year of stroke-related instruction and some didn¡¯t, a test showed the first group of children was much more likely to know how to recognize a stroke and to indicate they would call 911 if they witnessed someone having a stroke.
¡°Efforts to speed up patients¡¯ arrival at the hospital are absolutely crucial. We have very effective treatments, we just need to get patients to the hospital as fast as possible,¡± says Lewis Morgenstern, M.D., senior author of the hospital study and first author of the school study. ¡°Our first paper really speaks to the need to educate and motivate the public to call 911 for stroke, while the second shows one means to accomplish that goal.¡±
Both studies are from a community-based research effort funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. Researchers from the University of Texas at Houston and Eastern Michigan University are also involved.
The hospital study included 2,347 patients with ischemic (clot-based) strokes who reported to hospitals in the study area between January 2000 and June 2005. The average age was 71 years, and just over half were women. U-M stroke neurologist Jennifer Majersik, M.D., led the analysis.
The researchers reviewed medical records in detail, looking for information on what time each patient was last known to be without symptoms, and what time they reached the hospital. In some cases, when an exact time for the start of the symptoms was not known, the researchers used an estimate. They broke the patients up into groups by the time to presentation (arrival) at the hospital: less than three hours, three to six hours, six to 12 hours, and more than 12 hours.
The researchers also assessed how severe the patients¡¯ strokes were, and looked for differences in the time to hospital presentation for each severity group. The patients with the most severe strokes made it to the hospital in the fastest time, with nearly half of them making it in less than three hours. In contrast, only 28 percent of patients with the mildest level of stroke made it in that time. The study did not include patients who suffered transient ischemic attacks, also referred to as ¡°mini strokes.¡± Nor did it include patients with ¡°bleeding strokes¡± such as intracranial hemorrhages.
No matter what kind of stroke or mini-strokes patients have, the best course of action in all cases is to call 911, so that an ambulance or other emergency medical team can arrive and transport the patient to the hospital. Driving to the hospital oneself, or being driven by a friend or loved one, is less ideal because of delays that can occur en route or upon arrival at the hospital.
Even at major hospitals with dedicated 24-hour stroke teams, such as U-M, it can take an hour or more to use diagnostic tests to assess what type of stroke a patient is having and to start tPA treatment. At smaller hospitals, it can be more than an hour ¨C and intra-arterial tPA, which can be given up to six hours after the start of a stroke, may not be available.
So, a person experiencing a stroke really needs to get to a hospital within two hours of the start of a stroke to have the best chance of receiving tPA, says Morgenstern, who is a professor of neurology, emergency medicine and neurosurgery at the U-M Medical School and a member of the U-M Cardiovascular Center.
This kind of information, and the scientific reasons behind it, is what the public needs to hear from childhood on. That¡¯s why Morgenstern and his colleagues, including Kathleen Conley, Ph.D., of the School of Health Promotion and Human Performance at EMU, developed the ¡°Kids Identifying and Defeating Stroke¡± program, called KIDS for short.
The KIDS project involved middle schoolers in the Corpus Christi district, who were tested on three things: their knowledge of what a stroke is, their ability to identify stroke symptoms and their knowledge of what to do if someone around them appeared to be having a stroke.
One group was tested in both sixth and eighth grades but did not receive any specific in-school training about stroke. The other group was tested in sixth grade before receiving four hours of stroke education each year for three years as part of their school curriculum. They were tested again at the end of the three years. Parents of both groups were also approached for testing.
The students who had had the in-school training tested better in eighth grade than those who had not, with the most dramatic increase in correct answers seen in the part of the test that assessed whether students knew that calling 911 was the best option for responding to a stroke.
The students were also given homework assignments to share the stroke information with their parents or other adults, and assess their understanding of stroke. However, not enough of these assignments were completed to allow for a valid analysis.
Race Not a Factor in Liver Transplant Survival
ROCHESTER, Minn., Nov. 2 -- Race did not determine 10-year survival of liver transplant patients treated at four academic centers, a finding contrary to a previous major national analysis that favored Caucasian survival.
Action Points
Explain to patients that this study found no link between race and outcome following liver transplantation, but other published studies have reported a link.
Discuss the possibility that, as the authors suggest, the findings of this study reflect a select population, such as patients treated at top centers, and may not be generalizable to national outcomes.
The 10-year survival probability was 54.4% for African-Americans (95% CI 41.1-72.1%) versus 50.7% for Caucasians (95% CI 46.5-55.3) and 55.7% for other races (95% CI 41.5 74.8), according to W. Ray Kim, M.D., of the Mayo Clinic, and colleagues. The study was published in the November issue of Hepatology.
The finding emerged from an analysis of data from 2,823 orthotopic liver transplant patients who were prospectively enrolled in two multicenter databases. The patients were treated from 1985 through 2000.
Although there was no association between race and survival during the entire study period, non-Caucasian race was associated with a worse survival among non-black minority patients who received transplants before 1994 (HR=1.60, P 0.01), the investigators wrote. But this association was attenuated when diagnoses (hepatitis B and hepatocellular carcinoma) were included in the model, (HR=1.39, P =0.04).
Athough the results directly contradicted a published report that used the United Network Organ Sharing (UNOS) database, Dr. Kim defended his findings. "An examination of our Kaplan-Meier curves and multivariable HRs indicated that the lack of a difference between Caucasian and African races that we observed was not a result of insufficient power," even though his sample size was much smaller --135 African-American patients versus 1,042 in the UNOS data.
Moreover, he said that a post hoc sample size calculation confirmed that "our sample size had enough power to detect a difference of 10% in survival, which was about the size of the difference in outcome in the UNOS report."
There was, however, a major difference between the two studies. Patients in the Kim study were from "select, high-volume academic centers, which would be expected to provide better outcomes than the national average."
In addition to the 135 African-American patients, the Kim study included data on 2,448 Caucasians and 240 minority non-black patients.
Dr. Kim and colleagues collected demographic data as well as liver disease diagnoses, and post-transplant follow-up on all patients.
They compared survival across races and found that survival was slightly higher for non-Caucasians at one year and 10 years, while Caucasians had a slight survival edge at five years -- but none of the differences was statistically significant.
Among the findings:
At one year, survival for African-Americans was 90.8% versus 86.5% for Caucasians, and 84.4% for other minorities.
The five-year survival probability was 69.2% for African-Americans (95% CI: 60.1-79.7) versus 72.2% (95% CI 70.1-74.4); and 67.5% for other races (95% CI60.5-75.3).
There was no difference in patient survival (P=0.162) or graft survival (P=0.582) among the racial groups.
Compared with recipients with viral hepatitis, patients with cholestatic disease or other liver disease categories had significantly better survival (P0.01).
"As proof of principle, our data, although put together from difference databases from different time periods, indicted that [orthotopic liver transplantation] recipients of a minority race, especially the African race, should not necessarily be expected to have poorer survival than Caucasians," Dr. Kim concluded.
Dr. Kim reported no potential conflicts of interest. The study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Additional source: HepatologySource reference: Lee, TH et al "Survival After Liver Transplantation: Is Racial Disparity Inevitable?" Hepatology 2007; 46:1491-1497
ROCHESTER, Minn., Nov. 2 -- Race did not determine 10-year survival of liver transplant patients treated at four academic centers, a finding contrary to a previous major national analysis that favored Caucasian survival.
Action Points
Explain to patients that this study found no link between race and outcome following liver transplantation, but other published studies have reported a link.
Discuss the possibility that, as the authors suggest, the findings of this study reflect a select population, such as patients treated at top centers, and may not be generalizable to national outcomes.
The 10-year survival probability was 54.4% for African-Americans (95% CI 41.1-72.1%) versus 50.7% for Caucasians (95% CI 46.5-55.3) and 55.7% for other races (95% CI 41.5 74.8), according to W. Ray Kim, M.D., of the Mayo Clinic, and colleagues. The study was published in the November issue of Hepatology.
The finding emerged from an analysis of data from 2,823 orthotopic liver transplant patients who were prospectively enrolled in two multicenter databases. The patients were treated from 1985 through 2000.
Although there was no association between race and survival during the entire study period, non-Caucasian race was associated with a worse survival among non-black minority patients who received transplants before 1994 (HR=1.60, P 0.01), the investigators wrote. But this association was attenuated when diagnoses (hepatitis B and hepatocellular carcinoma) were included in the model, (HR=1.39, P =0.04).
Athough the results directly contradicted a published report that used the United Network Organ Sharing (UNOS) database, Dr. Kim defended his findings. "An examination of our Kaplan-Meier curves and multivariable HRs indicated that the lack of a difference between Caucasian and African races that we observed was not a result of insufficient power," even though his sample size was much smaller --135 African-American patients versus 1,042 in the UNOS data.
Moreover, he said that a post hoc sample size calculation confirmed that "our sample size had enough power to detect a difference of 10% in survival, which was about the size of the difference in outcome in the UNOS report."
There was, however, a major difference between the two studies. Patients in the Kim study were from "select, high-volume academic centers, which would be expected to provide better outcomes than the national average."
In addition to the 135 African-American patients, the Kim study included data on 2,448 Caucasians and 240 minority non-black patients.
Dr. Kim and colleagues collected demographic data as well as liver disease diagnoses, and post-transplant follow-up on all patients.
They compared survival across races and found that survival was slightly higher for non-Caucasians at one year and 10 years, while Caucasians had a slight survival edge at five years -- but none of the differences was statistically significant.
Among the findings:
At one year, survival for African-Americans was 90.8% versus 86.5% for Caucasians, and 84.4% for other minorities.
The five-year survival probability was 69.2% for African-Americans (95% CI: 60.1-79.7) versus 72.2% (95% CI 70.1-74.4); and 67.5% for other races (95% CI60.5-75.3).
There was no difference in patient survival (P=0.162) or graft survival (P=0.582) among the racial groups.
Compared with recipients with viral hepatitis, patients with cholestatic disease or other liver disease categories had significantly better survival (P0.01).
"As proof of principle, our data, although put together from difference databases from different time periods, indicted that [orthotopic liver transplantation] recipients of a minority race, especially the African race, should not necessarily be expected to have poorer survival than Caucasians," Dr. Kim concluded.
Dr. Kim reported no potential conflicts of interest. The study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Additional source: HepatologySource reference: Lee, TH et al "Survival After Liver Transplantation: Is Racial Disparity Inevitable?" Hepatology 2007; 46:1491-1497
Friday, November 02, 2007
Reducing Hypertrophy in Hypertension Patients May Shrink Diabetes Risk
NEW YORK, Nov. 1 -- Regression or prevention of left-ventricular hypertrophy in hypertension patients may reduce their risk of developing new-onset diabetes, according to a study.
Action Points
The LIFE study from which these findings came reflects a potentially important association but do not establish causality between decreasing an enlarged heart and preventing new diabetes.
The risk of developing new-onset diabetes was reduced by 38% among those whose left-ventricular hypertrophy regressed during hypertension treatment with losartan (Cozaar, Hyzaar), Peter Okin, M.D., of Cornell University Medical Center here, and colleagues, reported in the November issue of Hypertension.
After adjusting for drug treatment, blood pressure lowering, and diabetes risk factors, the risk, though attenuated, was still 26% lower, the researchers reported.
The Cornell study, supported in part by Merck, maker of losartan, used data from the blinded Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study.
The LIFE study, conducted from 1995 through 2001, of losartan versus atenolol-based therapy for hypertensive patients with left- ventricular hypertrophy, found losartan therapy associated with a lower incidence of diabetes and greater regression of hypertrophy.
But whether treatment resolution or continued absence of hypertrophy is independently associated with a decreased incidence of diabetes remained unclear, Dr. Okin said.
Accordingly, the present study evaluated hypertrophy in 7,998 hypertensive patients without diabetes at baseline in the LIFE study who were treated with losartan-based or atenolol-based regimens and followed with serial electrocardiograms and blood pressure determinations.
Electrocardiographic hypertrophy was defined using gender-adjusted Cornell voltage-duration criteria > 2,440 mm.ms.
During mean follow-up of 4.6 ± 1.2 years, 562 patients (7%) developed diabetes.
In a Cox model adjusting for drug treatment assignment, in-treatment resolution or continued absence of hypertrophy was associated with a 38% lower risk of new diabetes (HR 0.62, 95% CI 0.50 to 0.78).
After adjusting for the association of new diabetes with a series of risk confounders, continued absence or resolution of hypertrophy remained associated with a 26% lower risk of new diabetes (HR 0.74, 95% CI 0.58 to 0.93), the researchers reported.
Confounders included prior antihypertensive treatment, baseline glucose, Framingham risk score, baseline and in-treatment systolic and diastolic pressure, HDL, uric acid, body mass index, and, also, the decreased incidence associated with losartan-based therapy.
Thus, compared with the presence of hypertrophy during antihypertensive treatment, resolution or continued absence of hypertrophy was associated with a lower rate of diabetes, even after adjusting for the impact of treatment with losartan and other diabetes risk factors, the researcher said.
In contrast, higher values of left-ventricular hypertrophy were associated with higher rates of new diabetes, they said.
Study limitations included the fact that the study population was mainly white and was derived from a high-risk population.
Also, the researchers emphasized that the favorable association reported was attenuated after adjustment for other risk factors, and the LIFE study was not designed to test whether treatment specifically aimed at producing regression of hypertrophy will decrease the incidence of diabetes.
As a result, they said, these findings reflect a potentially important association but do not establish causality between resolution of hypertrophy and diabetes.
These results and previous findings with ACE-inhibitor and angiotensin-receptor-blocker therapy, they added, suggest that antihypertensive therapies that independently reduce the occurrence of diabetes and also produce left-ventricular hypertrophy regression may provide long-term benefits by reducing cardiovascular morbidity and mortality, at least in part by preventing new-onset diabetes.
Further study will be necessary to determine whether regression of hypertrophy will become a valid independent target for therapeutic intervention in hypertensive patients to prevent development of diabetes and other adverse cardiovascular outcomes, the researchers concluded.
This study was supported in part by a grant from Merck, maker of losartan. The drug maker took no part in the interpretation or writing of the study. Dr. Okin reported that he has received grant support from Merck while other study authors reported various financial relationships with Merck.Primary source: HypertensionSource reference: Okin PM, et al "In-Treatment Resolution or Absence of Electrocardiographic Left Ventricular Hypertrophy Is Associated With Decreased Incidence of New-Onset Diabetes Mellitus in Hypertensive Patients: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study"Hypertension 2007; 50: 984-990.
NEW YORK, Nov. 1 -- Regression or prevention of left-ventricular hypertrophy in hypertension patients may reduce their risk of developing new-onset diabetes, according to a study.
Action Points
The LIFE study from which these findings came reflects a potentially important association but do not establish causality between decreasing an enlarged heart and preventing new diabetes.
The risk of developing new-onset diabetes was reduced by 38% among those whose left-ventricular hypertrophy regressed during hypertension treatment with losartan (Cozaar, Hyzaar), Peter Okin, M.D., of Cornell University Medical Center here, and colleagues, reported in the November issue of Hypertension.
After adjusting for drug treatment, blood pressure lowering, and diabetes risk factors, the risk, though attenuated, was still 26% lower, the researchers reported.
The Cornell study, supported in part by Merck, maker of losartan, used data from the blinded Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study.
The LIFE study, conducted from 1995 through 2001, of losartan versus atenolol-based therapy for hypertensive patients with left- ventricular hypertrophy, found losartan therapy associated with a lower incidence of diabetes and greater regression of hypertrophy.
But whether treatment resolution or continued absence of hypertrophy is independently associated with a decreased incidence of diabetes remained unclear, Dr. Okin said.
Accordingly, the present study evaluated hypertrophy in 7,998 hypertensive patients without diabetes at baseline in the LIFE study who were treated with losartan-based or atenolol-based regimens and followed with serial electrocardiograms and blood pressure determinations.
Electrocardiographic hypertrophy was defined using gender-adjusted Cornell voltage-duration criteria > 2,440 mm.ms.
During mean follow-up of 4.6 ± 1.2 years, 562 patients (7%) developed diabetes.
In a Cox model adjusting for drug treatment assignment, in-treatment resolution or continued absence of hypertrophy was associated with a 38% lower risk of new diabetes (HR 0.62, 95% CI 0.50 to 0.78).
After adjusting for the association of new diabetes with a series of risk confounders, continued absence or resolution of hypertrophy remained associated with a 26% lower risk of new diabetes (HR 0.74, 95% CI 0.58 to 0.93), the researchers reported.
Confounders included prior antihypertensive treatment, baseline glucose, Framingham risk score, baseline and in-treatment systolic and diastolic pressure, HDL, uric acid, body mass index, and, also, the decreased incidence associated with losartan-based therapy.
Thus, compared with the presence of hypertrophy during antihypertensive treatment, resolution or continued absence of hypertrophy was associated with a lower rate of diabetes, even after adjusting for the impact of treatment with losartan and other diabetes risk factors, the researcher said.
In contrast, higher values of left-ventricular hypertrophy were associated with higher rates of new diabetes, they said.
Study limitations included the fact that the study population was mainly white and was derived from a high-risk population.
Also, the researchers emphasized that the favorable association reported was attenuated after adjustment for other risk factors, and the LIFE study was not designed to test whether treatment specifically aimed at producing regression of hypertrophy will decrease the incidence of diabetes.
As a result, they said, these findings reflect a potentially important association but do not establish causality between resolution of hypertrophy and diabetes.
These results and previous findings with ACE-inhibitor and angiotensin-receptor-blocker therapy, they added, suggest that antihypertensive therapies that independently reduce the occurrence of diabetes and also produce left-ventricular hypertrophy regression may provide long-term benefits by reducing cardiovascular morbidity and mortality, at least in part by preventing new-onset diabetes.
Further study will be necessary to determine whether regression of hypertrophy will become a valid independent target for therapeutic intervention in hypertensive patients to prevent development of diabetes and other adverse cardiovascular outcomes, the researchers concluded.
This study was supported in part by a grant from Merck, maker of losartan. The drug maker took no part in the interpretation or writing of the study. Dr. Okin reported that he has received grant support from Merck while other study authors reported various financial relationships with Merck.Primary source: HypertensionSource reference: Okin PM, et al "In-Treatment Resolution or Absence of Electrocardiographic Left Ventricular Hypertrophy Is Associated With Decreased Incidence of New-Onset Diabetes Mellitus in Hypertensive Patients: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study"Hypertension 2007; 50: 984-990.
FDA Approves Nilotinib (Tasigna) for Second-Line CML
ROCKVILLE, Md., Nov. 1 -- The FDA has approved nilotinib (Tasigna) for Philadelphia chromosome-positive chronic myeloid leukemia that is refractory or resistant to imatinib (Gleevec) or other first-line treatments.
As part of the approval, the FDA stipulated that nilotinib carry a black box warning for "possible life-threatening heart problems that may lead to an irregular heartbeat and possible sudden death."
The FDA based its decision on efficacy demonstrated in ongoing trials of nilotinib. It said responses in those trials were "associated with normalization of blood counts and bone marrow examinations." But the FDA said additional follow-up of patients was needed to determine the durability of those responses.
According to the FDA, patients may lower their chances for the heart problems by taking nilotinib without food, and by avoiding grapefruit products.
"Patients should also consult with their physician or other health care professional about avoiding other medications that can cause heart problems when taking [nilotinib]," the FDA said.
Moreover, patients with low blood potassium or magnesium should not use nilotinib.
The most common side effects in clinical trials included low blood counts, rash, headache, nausea and itching. Other possible serious side effects included liver damage, edema, and pancreas inflammation.
The FDA said women should not take the drug while pregnant, nor should they take it while breastfeeding.
ROCKVILLE, Md., Nov. 1 -- The FDA has approved nilotinib (Tasigna) for Philadelphia chromosome-positive chronic myeloid leukemia that is refractory or resistant to imatinib (Gleevec) or other first-line treatments.
As part of the approval, the FDA stipulated that nilotinib carry a black box warning for "possible life-threatening heart problems that may lead to an irregular heartbeat and possible sudden death."
The FDA based its decision on efficacy demonstrated in ongoing trials of nilotinib. It said responses in those trials were "associated with normalization of blood counts and bone marrow examinations." But the FDA said additional follow-up of patients was needed to determine the durability of those responses.
According to the FDA, patients may lower their chances for the heart problems by taking nilotinib without food, and by avoiding grapefruit products.
"Patients should also consult with their physician or other health care professional about avoiding other medications that can cause heart problems when taking [nilotinib]," the FDA said.
Moreover, patients with low blood potassium or magnesium should not use nilotinib.
The most common side effects in clinical trials included low blood counts, rash, headache, nausea and itching. Other possible serious side effects included liver damage, edema, and pancreas inflammation.
The FDA said women should not take the drug while pregnant, nor should they take it while breastfeeding.
Circadian Rhythm Sleep Disorders Get New Guidelines
ROCHESTER, Minn., Nov. 1 -- The first comprehensive guidelines for circadian rhythm sleep disorders are out, though with few surprises for sleep medicine specialists.
Action Points
Explain to interested patients that the guidelines provide a more comprehensive approach to circadian rhythm sleep disorders than was previously available.
Consider recommendations from the American Academy of Sleep Medicine in diagnosis and treatment of circadian rhythm sleep disorders.
Nonetheless, the American Academy of Sleep Medicine recommendations may be helpful for clinicians in treating and diagnosing shift work disorder and in the use of melatonin, said Timothy I. Morgenthaler, M.D., of the Mayo Clinic here.
He and colleagues developed the practice parameters because research in the relatively new but growing field of sleep medicine has outpaced clinical developments, they wrote in the Nov. 1 issue of SLEEP.
"Many of the [existing] practice parameters had to do with diagnostic procedures, [and] some of them had to do with very specific therapeutic endeavors," Dr. Morgenthaler said, but there were no cohesive evidence-based guidelines.
The guidelines were developed from two review articles to be published in the same journal issue.
One encompassed exogenous circadian rhythm sleep disorders (shift work disorder and jet lag disorder). The other dealt with endogenous circadian rhythm sleep disorders, which included advanced sleep phase disorder, delayed sleep phase disorder, irregular sleep-wake rhythm, and the non-24-hour sleep-wake syndrome (free-running disorder).
The recommendations were divided by level of evidence into standards that were backed by high-quality randomized controlled trials or well-validated cohorts; guidelines that were supported with only cohort studies or flawed clinical trials; and options, defined by inconclusive or conflicting evidence or conflicting expert opinion.
Melatonin was recommended as indicated across the spectrum of circadian rhythm sleep disorders, except for irregular sleep-wake rhythm disorder in elderly patients with dementia or those in nursing homes. These recommendations were considered options for advanced sleep phase, free-running disorder in sighted patients, and for irregular sleep-wake rhythm patients with moderate to severe mental retardation.
For shift work sleep disorder, actigraphy was recommended for diagnosis and monitoring response to therapy, as was use of a sleep log or diary. But polysomnography, Morningness-Eveningness Questionnaires, and circadian phase markers were not recommended for routine use.
Planned sleep schedules were considered a standard therapy for shift work sleep disorder whereas use of timed light exposure and melatonin, hypnotics, and alerting agents had a lower level of evidence. Caffeine, modafinil (Provigil), and methamphetamine were suggested as options for treatment.
Overall, the standard for polysomnography use was to rule out another primary sleep disorder but not for routine diagnosis of circadian rhythm sleep disorders.
Other guidelines included:
Use of a sleep log or diary to assess patients with a suspected CRSD.
Actigraphy for diagnosis of circadian rhythm disorders aside from jet lag and for evaluating response to treatment across the board.
Morning light exposure for treatment of delayed sleep phase disorder.
Other recommendations at the option level of evidence included:
Maintaining home-based rather than destination sleep hours to combat jet lag when the duration of a trip is expected to be brief.
The combination of morning exposure to bright light and shifting the sleep one hour earlier each day for three days prior to eastward travel to lessen jet lag symptoms.
For advanced sleep phase disorder, use of prescribed sleep-wake scheduling, timed light exposure, or timed melatonin administration.
Progressive delay in scheduled sleep time (chronotherapy) for delayed sleep phase disorders.
For free-running disorder, use of sleep logs and circadian phase markers for assessment and prescribed sleep-wake scheduling as treatment for sighted patients and timed light exposure or melatonin for treatment of both blind and sighted patients.
Daytime light exposure for nursing home residents with dementia and irregular sleep-wake rhythm disorder.
All members of the AASM Standards of Practice Committee and Board of Directors completed detailed conflict of interest statements and were found to have no conflicts of interest with regard to this subject.
Primary source: SLEEPSource reference: Morgenthaler TI, et al "Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders: An American Academy of Sleep Medicine Report" Sleep 2007.
ROCHESTER, Minn., Nov. 1 -- The first comprehensive guidelines for circadian rhythm sleep disorders are out, though with few surprises for sleep medicine specialists.
Action Points
Explain to interested patients that the guidelines provide a more comprehensive approach to circadian rhythm sleep disorders than was previously available.
Consider recommendations from the American Academy of Sleep Medicine in diagnosis and treatment of circadian rhythm sleep disorders.
Nonetheless, the American Academy of Sleep Medicine recommendations may be helpful for clinicians in treating and diagnosing shift work disorder and in the use of melatonin, said Timothy I. Morgenthaler, M.D., of the Mayo Clinic here.
He and colleagues developed the practice parameters because research in the relatively new but growing field of sleep medicine has outpaced clinical developments, they wrote in the Nov. 1 issue of SLEEP.
"Many of the [existing] practice parameters had to do with diagnostic procedures, [and] some of them had to do with very specific therapeutic endeavors," Dr. Morgenthaler said, but there were no cohesive evidence-based guidelines.
The guidelines were developed from two review articles to be published in the same journal issue.
One encompassed exogenous circadian rhythm sleep disorders (shift work disorder and jet lag disorder). The other dealt with endogenous circadian rhythm sleep disorders, which included advanced sleep phase disorder, delayed sleep phase disorder, irregular sleep-wake rhythm, and the non-24-hour sleep-wake syndrome (free-running disorder).
The recommendations were divided by level of evidence into standards that were backed by high-quality randomized controlled trials or well-validated cohorts; guidelines that were supported with only cohort studies or flawed clinical trials; and options, defined by inconclusive or conflicting evidence or conflicting expert opinion.
Melatonin was recommended as indicated across the spectrum of circadian rhythm sleep disorders, except for irregular sleep-wake rhythm disorder in elderly patients with dementia or those in nursing homes. These recommendations were considered options for advanced sleep phase, free-running disorder in sighted patients, and for irregular sleep-wake rhythm patients with moderate to severe mental retardation.
For shift work sleep disorder, actigraphy was recommended for diagnosis and monitoring response to therapy, as was use of a sleep log or diary. But polysomnography, Morningness-Eveningness Questionnaires, and circadian phase markers were not recommended for routine use.
Planned sleep schedules were considered a standard therapy for shift work sleep disorder whereas use of timed light exposure and melatonin, hypnotics, and alerting agents had a lower level of evidence. Caffeine, modafinil (Provigil), and methamphetamine were suggested as options for treatment.
Overall, the standard for polysomnography use was to rule out another primary sleep disorder but not for routine diagnosis of circadian rhythm sleep disorders.
Other guidelines included:
Use of a sleep log or diary to assess patients with a suspected CRSD.
Actigraphy for diagnosis of circadian rhythm disorders aside from jet lag and for evaluating response to treatment across the board.
Morning light exposure for treatment of delayed sleep phase disorder.
Other recommendations at the option level of evidence included:
Maintaining home-based rather than destination sleep hours to combat jet lag when the duration of a trip is expected to be brief.
The combination of morning exposure to bright light and shifting the sleep one hour earlier each day for three days prior to eastward travel to lessen jet lag symptoms.
For advanced sleep phase disorder, use of prescribed sleep-wake scheduling, timed light exposure, or timed melatonin administration.
Progressive delay in scheduled sleep time (chronotherapy) for delayed sleep phase disorders.
For free-running disorder, use of sleep logs and circadian phase markers for assessment and prescribed sleep-wake scheduling as treatment for sighted patients and timed light exposure or melatonin for treatment of both blind and sighted patients.
Daytime light exposure for nursing home residents with dementia and irregular sleep-wake rhythm disorder.
All members of the AASM Standards of Practice Committee and Board of Directors completed detailed conflict of interest statements and were found to have no conflicts of interest with regard to this subject.
Primary source: SLEEPSource reference: Morgenthaler TI, et al "Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders: An American Academy of Sleep Medicine Report" Sleep 2007.
Anxious Personality Predisposes to Sleep Disturbance After Major Stress
TURKU, Finland, Nov. 1 -- People who tend to experience daily life as highly stressful may be more likely to develop sleep problems when traumatic events occur, researchers found.However, the 1.5- to three-fold increased risk may persist only for the first months after a stressful event, such as divorce or family illness, reported Jussi Vahtera, M.D., of the Finnish Institute of Occupational Health here, and colleagues in the November 1 issue of the journal SLEEP.
Action Points
Explain to interested patients that their daily experience of anxiety may impact their sleep after a major stressful event.
Inform patients that the study did not look at whether treating an ingrained tendency toward anxiety or sleep disturbance could impact the effects of a major stressful life event.
These findings from a large, population-based study provide prospective evidence that people who are anxious by nature are predisposed to sleep disturbances, the researchers said.
They analyzed data from the longitudinal Health and Social Support study with a representative sample of the Finnish population. The analysis included 19,199 respondents who completed a survey both at baseline in 1998 and five years later.
At baseline, participants fell into four age groups -- 20 to 24, 30 to 34, 40 to 44, or 50 to 54 -- and 13% reported sleep disturbances. At follow-up, 11% reported new-onset sleep disturbances.
Liability to anxiety, indicated by a general feeling of stressfulness (as measured by the Reeder stress inventory) and symptoms of sympathetic nervous system hyperactivity, was strongly linked to disturbed sleep, the researchers said.
Men and women with the highest levels of general stress on a day-to-day basis were 2.4 times more likely to develop new-onset sleep disturbances compared with those in the lowest quartile (95% confidence interval 2.0 to 2.7). For symptoms of sympathetic nervous system hyperactivity, the odds of developing sleep disturbances were 2.2 times higher for those in the highest quartile than for those in the lowest quartile (95% CI 1.9 to 2.5).
Anxiety also increased risk for persistent sleep disturbances.
Respondents with the most symptoms of sympathetic nervous system hyperactivity were 1.5 times more likely to have sleep disturbances that persisted from baseline through five-year follow-up than those in the lowest quartile of this measure of anxiousness (95% CI 1.2 to 1.8).
Stressful events appeared to trigger problems sleeping, particularly for those who reported a high liability to anxiety.
From baseline to six months before the five-year follow-up, 13,180 participants reported a severe stressful event, such as death or illness in the family, divorce or separation, financial difficulties, or emotional, physical, or sexual violence. Participants who reported events related to changes in their health, which could impact sleep, were excluded.
Another 5,642 patients had a major stressful event in the six months before the follow-up. Among them, 71% experienced one event, 20% reported two events, and the remainder had up to eight events.
For participants who did not have pre-existing sleep problems, cumulative exposure to stressful events linearly increased with risk of sleep disturbances and was about double the risk of unexposed participants whether the events were recent or not.
The association did not appear to be entirely explained by controlling for anxiety and other predictors of sleep disturbances, which reduced the associations by no more than 33% to 39%, the researchers said. Nor were the associations explained by depression.
Death or illness in the family, divorce, and financial difficulties were independent predictors of new-onset sleep disturbances over the longer term, whereas financial difficulties were independently associated with sleep over the shorter term.
For men and women with pre-existing sleep disturbances at baseline, stressful life events were also associated with a 1.6- to two-fold increase in risk of persistent sleep problems at the five-year follow-up, "but only if the event had occurred within six months," the researchers noted.
Anxious people who experienced stressful events had the greatest likelihood of sleep disturbance over the short term.
For men who reported a negative life event, the odds were 3.11 times higher for those with a high general feeling of stressfulness (95% CI 1.90 to 5.10) and 2.88 times higher for those with sympathetic nervous system hyperactivity (95% CI 1.69-4.91) than for those with no exposure to stressful life events.
By comparison, severe life events did not increase likelihood of new-onset sleep disturbance among men not prone to anxiety.
For women in the study, liability to anxiety in combination with stressful events in the prior six months raised the risk of new-onset sleep problems 1.54- to 2.38-fold (95% CI 1.07 to 4.13).
Although acute sleep problems may increase risk of chronic sleep disturbances, liability to anxiety was not linked to sleep disturbance and life events long term (P>0.10).
"This heightened vulnerability was evident, however, only zero to six months after the event," Dr. Vahtera and colleagues wrote.
Dr. Vahtera and a co-author reported support from the Academy of Finland.Primary source: SLEEPSource reference: Vahtera J, et al "Liability to Anxiety and Severe Life Events as Predictors of New-Onset Sleep Disturbances" SLEEP 2007; 30: 1449-1458.
TURKU, Finland, Nov. 1 -- People who tend to experience daily life as highly stressful may be more likely to develop sleep problems when traumatic events occur, researchers found.However, the 1.5- to three-fold increased risk may persist only for the first months after a stressful event, such as divorce or family illness, reported Jussi Vahtera, M.D., of the Finnish Institute of Occupational Health here, and colleagues in the November 1 issue of the journal SLEEP.
Action Points
Explain to interested patients that their daily experience of anxiety may impact their sleep after a major stressful event.
Inform patients that the study did not look at whether treating an ingrained tendency toward anxiety or sleep disturbance could impact the effects of a major stressful life event.
These findings from a large, population-based study provide prospective evidence that people who are anxious by nature are predisposed to sleep disturbances, the researchers said.
They analyzed data from the longitudinal Health and Social Support study with a representative sample of the Finnish population. The analysis included 19,199 respondents who completed a survey both at baseline in 1998 and five years later.
At baseline, participants fell into four age groups -- 20 to 24, 30 to 34, 40 to 44, or 50 to 54 -- and 13% reported sleep disturbances. At follow-up, 11% reported new-onset sleep disturbances.
Liability to anxiety, indicated by a general feeling of stressfulness (as measured by the Reeder stress inventory) and symptoms of sympathetic nervous system hyperactivity, was strongly linked to disturbed sleep, the researchers said.
Men and women with the highest levels of general stress on a day-to-day basis were 2.4 times more likely to develop new-onset sleep disturbances compared with those in the lowest quartile (95% confidence interval 2.0 to 2.7). For symptoms of sympathetic nervous system hyperactivity, the odds of developing sleep disturbances were 2.2 times higher for those in the highest quartile than for those in the lowest quartile (95% CI 1.9 to 2.5).
Anxiety also increased risk for persistent sleep disturbances.
Respondents with the most symptoms of sympathetic nervous system hyperactivity were 1.5 times more likely to have sleep disturbances that persisted from baseline through five-year follow-up than those in the lowest quartile of this measure of anxiousness (95% CI 1.2 to 1.8).
Stressful events appeared to trigger problems sleeping, particularly for those who reported a high liability to anxiety.
From baseline to six months before the five-year follow-up, 13,180 participants reported a severe stressful event, such as death or illness in the family, divorce or separation, financial difficulties, or emotional, physical, or sexual violence. Participants who reported events related to changes in their health, which could impact sleep, were excluded.
Another 5,642 patients had a major stressful event in the six months before the follow-up. Among them, 71% experienced one event, 20% reported two events, and the remainder had up to eight events.
For participants who did not have pre-existing sleep problems, cumulative exposure to stressful events linearly increased with risk of sleep disturbances and was about double the risk of unexposed participants whether the events were recent or not.
The association did not appear to be entirely explained by controlling for anxiety and other predictors of sleep disturbances, which reduced the associations by no more than 33% to 39%, the researchers said. Nor were the associations explained by depression.
Death or illness in the family, divorce, and financial difficulties were independent predictors of new-onset sleep disturbances over the longer term, whereas financial difficulties were independently associated with sleep over the shorter term.
For men and women with pre-existing sleep disturbances at baseline, stressful life events were also associated with a 1.6- to two-fold increase in risk of persistent sleep problems at the five-year follow-up, "but only if the event had occurred within six months," the researchers noted.
Anxious people who experienced stressful events had the greatest likelihood of sleep disturbance over the short term.
For men who reported a negative life event, the odds were 3.11 times higher for those with a high general feeling of stressfulness (95% CI 1.90 to 5.10) and 2.88 times higher for those with sympathetic nervous system hyperactivity (95% CI 1.69-4.91) than for those with no exposure to stressful life events.
By comparison, severe life events did not increase likelihood of new-onset sleep disturbance among men not prone to anxiety.
For women in the study, liability to anxiety in combination with stressful events in the prior six months raised the risk of new-onset sleep problems 1.54- to 2.38-fold (95% CI 1.07 to 4.13).
Although acute sleep problems may increase risk of chronic sleep disturbances, liability to anxiety was not linked to sleep disturbance and life events long term (P>0.10).
"This heightened vulnerability was evident, however, only zero to six months after the event," Dr. Vahtera and colleagues wrote.
Dr. Vahtera and a co-author reported support from the Academy of Finland.Primary source: SLEEPSource reference: Vahtera J, et al "Liability to Anxiety and Severe Life Events as Predictors of New-Onset Sleep Disturbances" SLEEP 2007; 30: 1449-1458.
Risperidone as Augmentive Therapy for Depression
Risperidone improved measures of depression and response in patients with treatment-refractory depression, according to a report in Annals of Internal Medicine.
The multicenter trial, sponsored and conducted by the manufacturer, randomized some 268 outpatients with refractory disease either to augmentation therapy with low-dose risperidone or to placebo for 6 weeks.
Hamilton rating scale measures of depression were more improved at 4- and 6-week assessments among those on risperidone than those on placebo. Similarly, rates of remission and the proportion of patients responding to treatment favored risperidone. Patients reported better overall life satisfaction on the drug. Complications included dry mouth and somnolence.
The journal's editors point to the trial's brevity, but conclude, with the study authors, that augmentation with risperidone was associated with improvements in some patients. (The authors calculate an NNT of 7 to achieve a remission.)
Risperidone improved measures of depression and response in patients with treatment-refractory depression, according to a report in Annals of Internal Medicine.
The multicenter trial, sponsored and conducted by the manufacturer, randomized some 268 outpatients with refractory disease either to augmentation therapy with low-dose risperidone or to placebo for 6 weeks.
Hamilton rating scale measures of depression were more improved at 4- and 6-week assessments among those on risperidone than those on placebo. Similarly, rates of remission and the proportion of patients responding to treatment favored risperidone. Patients reported better overall life satisfaction on the drug. Complications included dry mouth and somnolence.
The journal's editors point to the trial's brevity, but conclude, with the study authors, that augmentation with risperidone was associated with improvements in some patients. (The authors calculate an NNT of 7 to achieve a remission.)
Guidelines for COPD Management
Guidelines for managing stable chronic obstructive pulmonary disease, released by the American College of Physicians, appear in the current issue of Annals of Internal Medicine.
Based on a literature review published in the same issue, the guidelines recommend:
using spirometry to diagnose — but not to screen asymptomatic patients for — airflow obstruction;
reserving treatment for symptomatic patients with FEV1 below 60% predicted;
treating patients with inhaled monotherapy comprising long-acting beta-agonists, anticholinergics, or corticosteroids (combination therapy may be considered);
using oxygen therapy in patients with resting hypoxemia;
limiting use of pulmonary rehab to symptomatic patients with FEV1 under 50% predicted.
The literature reviewers note that although monotherapy reduces exacerbations, it does not reduce mortality rates. For its part, oxygen therapy, used for at least 15 hours daily, reduces mortality in patients with resting hypoxemia and FEV1 under 30% predicted.
Guidelines for managing stable chronic obstructive pulmonary disease, released by the American College of Physicians, appear in the current issue of Annals of Internal Medicine.
Based on a literature review published in the same issue, the guidelines recommend:
using spirometry to diagnose — but not to screen asymptomatic patients for — airflow obstruction;
reserving treatment for symptomatic patients with FEV1 below 60% predicted;
treating patients with inhaled monotherapy comprising long-acting beta-agonists, anticholinergics, or corticosteroids (combination therapy may be considered);
using oxygen therapy in patients with resting hypoxemia;
limiting use of pulmonary rehab to symptomatic patients with FEV1 under 50% predicted.
The literature reviewers note that although monotherapy reduces exacerbations, it does not reduce mortality rates. For its part, oxygen therapy, used for at least 15 hours daily, reduces mortality in patients with resting hypoxemia and FEV1 under 30% predicted.
Thursday, November 01, 2007
Incidental Findings Common with Brain MRI
ROTTERDAM, Netherlands, Oct. 31 -- Incidental brain findings on MRI may be common once people hit middle age, although it is unclear what clinicians should do about such findings, researchers said.
MRI showed asymptomatic strokes in 7.2% of the general population in Rotterdam, according to a population-based study published in the Nov. 1 issue of the New England Journal of Medicine.
The prevalence of incidentally discovered cerebral aneurysms was 1.8% and for benign tumors it was 1.6%, reported Aad van der Lugt, M.D., of Erasmus MC University Medical Center here, and colleagues.
Overall, the results suggest that one in every 7.3 asymptomatic persons scanned will have an incidental finding, commented Adrian A. Jarquin-Valdivia, M.D., R.D.M.S., of Vanderbilt University in Nashville, Tenn., a spokesperson for the American Academy of Neurology, in an interview with MedPage Today.
Although these lesions are associated with an increased risk of adverse neurological events, "the clinical relevance and natural course of these unexpected asymptomatic findings are largely unknown," the researchers wrote.
Dr. van der Lugt's group analyzed incidental MRI findings in the Rotterdam Scan Study, which was designed to investigate age-related brain changes. It was embedded within the larger prospective, population-based Rotterdam Study.
The analysis included 2,000 participants ages 45 to 96 (mean 63.3), of whom 52.4% were women. The patients were continuously monitored for incident clinical stroke through a linked database with general practitioners and hospitals.
Overall, there were 272 incidental findings reported. The most common type was asymptomatic stroke (145 cases, 7.2%). Lacunar infarcts were more common than cortical infarcts (5.6% versus 2%).
Aneurysms were next most frequent at 1.8%. All but two of the 35 aneurysms were located in the anterior circulation, and only three were larger than 7 mm in diameter.
Benign tumors were a close runner-up with a rate of 1.6%. Meningiomas were most common (0.9%) and ranged in size from five to 60 mm in diameter.
MRI detected one possibly malignant primary brain tumor -- a low-grade glioma -- and one case of multiple cerebral metastases in a patient who had previously been treated for lung cancer.
The most urgent finding was a large, chronic subdural hematoma in a patient who was discovered to have had minor head trauma a month prior to the scan, the researchers said.
Other findings included:
Seven cases of cavernous angioma (0.4% prevalence)
22 cases of arachnoid cyst (1.1% prevalence)
18 type I Chiari malformations (0.9% prevalence)
Nine cases of major-vessel stenosis (0.5% prevalence)
One dermoid cyst of the lateral orbital rim (less than 0.1% prevalence)
One case of fibrous dysplasia (less than 0.1% prevalence)
White-matter lesions were found in all but 5.4% of participants ages 45 to 59 and all but 2% of those 75 and older. The prevalence of asymptomatic aneurysms and meningiomas increased with age as well.
Subclinical vascular pathologic changes have been linked to increased risk of stroke and cognitive decline, but preventive therapies have not been evaluated in randomized trials, they noted.
"Then the question becomes, is it worth knowing early?" Dr. Jarquin-Valdivia said.
For typically slow-growing, asymptomatic meningiomas, "the current practice of many clinicians is to perform MRI yearly for at least two to three years to ascertain that rapid tumor growth does not occur," Dr. van der Lugt and colleagues noted.
For otherwise healthy, asymptomatic adults, as in the study, the resulting medical costs and psychological burden suggest this practice may need to be reviewed, they said.
Risk of rupture for the small aneurysms found in the study is low and "preventive surgery or treatment of risk factors may thus not be indicated in the general population," the researchers added.
However, the story may be different for patients with subclinical strokes, Dr. Jarquin-Valdivia said.
Although it is not well known whether treating subclinical strokes would prevent future strokes, the findings from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that treating patients with symptomatic cerebrovascular disease with a combination of an ACE inhibitor and indapamide (Lozol) could prevent recurrent strokes (number-needed-to-treat 11).
If this were true for the asymptomatic patients in the Rotterdam study as well, "we could potentially have prevented 13 new symptomatic strokes over the course of one year," Dr. Jarquin-Valdivia concluded. "That may be worthwhile."
The study was supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission; the Municipality of Rotterdam; and by grants from the Netherlands Organization for Scientific Research.
The researchers reported no potential conflict of interest. Dr. Jarquin-Valdivia reported no conflicts of interest.Primary source: New England Journal of MedicineSource reference: Vernooij MW, et al "Incidental Findings on Brain MRI in the General Population" N Engl J Med 2007; 357: 1821-8.
ROTTERDAM, Netherlands, Oct. 31 -- Incidental brain findings on MRI may be common once people hit middle age, although it is unclear what clinicians should do about such findings, researchers said.
MRI showed asymptomatic strokes in 7.2% of the general population in Rotterdam, according to a population-based study published in the Nov. 1 issue of the New England Journal of Medicine.
The prevalence of incidentally discovered cerebral aneurysms was 1.8% and for benign tumors it was 1.6%, reported Aad van der Lugt, M.D., of Erasmus MC University Medical Center here, and colleagues.
Overall, the results suggest that one in every 7.3 asymptomatic persons scanned will have an incidental finding, commented Adrian A. Jarquin-Valdivia, M.D., R.D.M.S., of Vanderbilt University in Nashville, Tenn., a spokesperson for the American Academy of Neurology, in an interview with MedPage Today.
Although these lesions are associated with an increased risk of adverse neurological events, "the clinical relevance and natural course of these unexpected asymptomatic findings are largely unknown," the researchers wrote.
Dr. van der Lugt's group analyzed incidental MRI findings in the Rotterdam Scan Study, which was designed to investigate age-related brain changes. It was embedded within the larger prospective, population-based Rotterdam Study.
The analysis included 2,000 participants ages 45 to 96 (mean 63.3), of whom 52.4% were women. The patients were continuously monitored for incident clinical stroke through a linked database with general practitioners and hospitals.
Overall, there were 272 incidental findings reported. The most common type was asymptomatic stroke (145 cases, 7.2%). Lacunar infarcts were more common than cortical infarcts (5.6% versus 2%).
Aneurysms were next most frequent at 1.8%. All but two of the 35 aneurysms were located in the anterior circulation, and only three were larger than 7 mm in diameter.
Benign tumors were a close runner-up with a rate of 1.6%. Meningiomas were most common (0.9%) and ranged in size from five to 60 mm in diameter.
MRI detected one possibly malignant primary brain tumor -- a low-grade glioma -- and one case of multiple cerebral metastases in a patient who had previously been treated for lung cancer.
The most urgent finding was a large, chronic subdural hematoma in a patient who was discovered to have had minor head trauma a month prior to the scan, the researchers said.
Other findings included:
Seven cases of cavernous angioma (0.4% prevalence)
22 cases of arachnoid cyst (1.1% prevalence)
18 type I Chiari malformations (0.9% prevalence)
Nine cases of major-vessel stenosis (0.5% prevalence)
One dermoid cyst of the lateral orbital rim (less than 0.1% prevalence)
One case of fibrous dysplasia (less than 0.1% prevalence)
White-matter lesions were found in all but 5.4% of participants ages 45 to 59 and all but 2% of those 75 and older. The prevalence of asymptomatic aneurysms and meningiomas increased with age as well.
Subclinical vascular pathologic changes have been linked to increased risk of stroke and cognitive decline, but preventive therapies have not been evaluated in randomized trials, they noted.
"Then the question becomes, is it worth knowing early?" Dr. Jarquin-Valdivia said.
For typically slow-growing, asymptomatic meningiomas, "the current practice of many clinicians is to perform MRI yearly for at least two to three years to ascertain that rapid tumor growth does not occur," Dr. van der Lugt and colleagues noted.
For otherwise healthy, asymptomatic adults, as in the study, the resulting medical costs and psychological burden suggest this practice may need to be reviewed, they said.
Risk of rupture for the small aneurysms found in the study is low and "preventive surgery or treatment of risk factors may thus not be indicated in the general population," the researchers added.
However, the story may be different for patients with subclinical strokes, Dr. Jarquin-Valdivia said.
Although it is not well known whether treating subclinical strokes would prevent future strokes, the findings from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that treating patients with symptomatic cerebrovascular disease with a combination of an ACE inhibitor and indapamide (Lozol) could prevent recurrent strokes (number-needed-to-treat 11).
If this were true for the asymptomatic patients in the Rotterdam study as well, "we could potentially have prevented 13 new symptomatic strokes over the course of one year," Dr. Jarquin-Valdivia concluded. "That may be worthwhile."
The study was supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission; the Municipality of Rotterdam; and by grants from the Netherlands Organization for Scientific Research.
The researchers reported no potential conflict of interest. Dr. Jarquin-Valdivia reported no conflicts of interest.Primary source: New England Journal of MedicineSource reference: Vernooij MW, et al "Incidental Findings on Brain MRI in the General Population" N Engl J Med 2007; 357: 1821-8.
For MRSA Prevention, Clean Surfaces as Well as Hands
GLASGOW, Scotland, Oct. 31 -- Focusing more attention on cleaning door handles and other frequently-touched surfaces in hospitals may reduce transmission of methicillin-resistant Staphylococcus aureus (MRSA) beyond what can be accomplished by hand washing alone.
So reported Stephanie J. Dancer, M.D., of Southern General Hospital here, in a review published online in The Lancet Infectious Diseases.
Although clean hands are important, "introduction of additional cleaning services is easier than improvements in hand-hygiene compliance," she wrote.
The review came on the heels of increasing attention to MRSA in the media after outbreaks at Connecticut high schools and the death of a student in Virginia. (See: Survey Report: MRSA Publicity Will Make a Difference and Focus on Community-Acquired MRSA Was Preceded by Cadence of Concerns)
The focus was also turned on MRSA in the field of infectious diseases following a report earlier this month from the CDC that invasive MRSA was three times more common than previously estimated. (See: Invasive MRSA More Pervasive Than Suspected)
Despite all the attention, though, the importance of hospital cleaning is still debated, Dr. Dancer said.
"There is little direct evidence for the effectiveness of cleaning because it has never been afforded scientific status," she wrote.
Cleanliness of hospitals is usually assessed visually and is defined in cleaning manuals, monitoring strategies, and infection control guidelines, but dirt does not necessarily correlate with growth of MRSA or other pathogens, Dr. Dancer said.
One study, she noted, found that 82% to 91% of hospital wards were visibly clean but only 30% to 45% were considered microbiologically clean and just 10% to 24% were free from organic soil. Another study failed to correlate British hospital hygiene performance scores to MRSA rates.
The staphylococcal transmission cycle between people and their environment show that the disease is remarkably resilient and can be found on virtually all surfaces in hospitals, Dr. Dancer said.
Staphylococci bacteria can be found in the air and environment in which colonized patients live or through which they pass. There is "overwhelming" evidence, she said, for MRSA contamination on virtually all hospital surfaces, including door handles, television sets, beds, and paper.
On average, Dr. Dancer said, MRSA is found on about one-third of hospital surfaces sampled regardless of whether sampling occurred during an outbreak situation.
"The fact that most of these items can be touched by hands is important when considering the origin of MRSA contamination," she noted.
Infected patients most frequently carry the bacteria in their nose.
"Given the propensity for people to pick, touch, or blow their noses, it is not surprising that carriers will often harbor their own strain of S. aureus on their fingers, which they will then transfer to any site accessible to their hands," Dr. Dancer wrote.
But transmission is not limited to habitual carriers, because anyone who has just touched a contaminated site can contribute to the spread of bacteria as well, the researcher said.
Even if fingertips transport only a few colony-forming units of MRSA, as few as 10 could cause an infection.
All cleaning methods -- routine vacuuming and detergent-based cleaning, disinfectant-based deep cleaning, and decontamination with gaseous hydrogen peroxide -- have been shown to reduce MRSA in the hospital environment. Cutting down on the number of microbes present should reduce the risk of infection, Dr. Dancer said.
But, liquid disinfectants and detergents would damage the many types of electronic equipment, "providing more hand-touch sites that require a greater degree of sophisticated cleaning attention," she wrote.
Furthermore, MRSA risk lingers even at hospitals that exceeded CDC and Healthcare Infection Control Practices Advisory Committee standards for room cleaning procedures at discharge. (See: MRSA Risk Lingers from ICU Room's Prior Occupant)
And, the expense of extra cleaning can be prohibitive, especially in view of the current preoccupation with hospital budgets, she said.
Concentrating already available cleaning resources on high-risk hand-touch sites may be the most cost-effective cleaning strategy other than campaigning for more cleaning hours, she concluded.
"There can be no doubt that prioritizing hand hygiene is the single most beneficial intervention in the control of MRSA and many other pathogens," she said.
However, hand-hygiene initiatives have been less successful than environmental cleaning in some studies.
"And even if everyone does wash their hands properly, the effects of exemplary hand hygiene are eroded if the environment is heavily contaminated with MRSA," Dr. Dancer added.
Dr. Dancer reported no conflicts of interest.Primary source: The Lancet Infectious DiseasesSource reference: Dancer SJ, et al "Importance of the environment in methicillin-resistant Staphylococcus aureus acquisition: the case for hospital cleaning" Lancet Infect Dis 2007; DOI: 10.1016/S1473-3099(07)70241-4.
GLASGOW, Scotland, Oct. 31 -- Focusing more attention on cleaning door handles and other frequently-touched surfaces in hospitals may reduce transmission of methicillin-resistant Staphylococcus aureus (MRSA) beyond what can be accomplished by hand washing alone.
So reported Stephanie J. Dancer, M.D., of Southern General Hospital here, in a review published online in The Lancet Infectious Diseases.
Although clean hands are important, "introduction of additional cleaning services is easier than improvements in hand-hygiene compliance," she wrote.
The review came on the heels of increasing attention to MRSA in the media after outbreaks at Connecticut high schools and the death of a student in Virginia. (See: Survey Report: MRSA Publicity Will Make a Difference and Focus on Community-Acquired MRSA Was Preceded by Cadence of Concerns)
The focus was also turned on MRSA in the field of infectious diseases following a report earlier this month from the CDC that invasive MRSA was three times more common than previously estimated. (See: Invasive MRSA More Pervasive Than Suspected)
Despite all the attention, though, the importance of hospital cleaning is still debated, Dr. Dancer said.
"There is little direct evidence for the effectiveness of cleaning because it has never been afforded scientific status," she wrote.
Cleanliness of hospitals is usually assessed visually and is defined in cleaning manuals, monitoring strategies, and infection control guidelines, but dirt does not necessarily correlate with growth of MRSA or other pathogens, Dr. Dancer said.
One study, she noted, found that 82% to 91% of hospital wards were visibly clean but only 30% to 45% were considered microbiologically clean and just 10% to 24% were free from organic soil. Another study failed to correlate British hospital hygiene performance scores to MRSA rates.
The staphylococcal transmission cycle between people and their environment show that the disease is remarkably resilient and can be found on virtually all surfaces in hospitals, Dr. Dancer said.
Staphylococci bacteria can be found in the air and environment in which colonized patients live or through which they pass. There is "overwhelming" evidence, she said, for MRSA contamination on virtually all hospital surfaces, including door handles, television sets, beds, and paper.
On average, Dr. Dancer said, MRSA is found on about one-third of hospital surfaces sampled regardless of whether sampling occurred during an outbreak situation.
"The fact that most of these items can be touched by hands is important when considering the origin of MRSA contamination," she noted.
Infected patients most frequently carry the bacteria in their nose.
"Given the propensity for people to pick, touch, or blow their noses, it is not surprising that carriers will often harbor their own strain of S. aureus on their fingers, which they will then transfer to any site accessible to their hands," Dr. Dancer wrote.
But transmission is not limited to habitual carriers, because anyone who has just touched a contaminated site can contribute to the spread of bacteria as well, the researcher said.
Even if fingertips transport only a few colony-forming units of MRSA, as few as 10 could cause an infection.
All cleaning methods -- routine vacuuming and detergent-based cleaning, disinfectant-based deep cleaning, and decontamination with gaseous hydrogen peroxide -- have been shown to reduce MRSA in the hospital environment. Cutting down on the number of microbes present should reduce the risk of infection, Dr. Dancer said.
But, liquid disinfectants and detergents would damage the many types of electronic equipment, "providing more hand-touch sites that require a greater degree of sophisticated cleaning attention," she wrote.
Furthermore, MRSA risk lingers even at hospitals that exceeded CDC and Healthcare Infection Control Practices Advisory Committee standards for room cleaning procedures at discharge. (See: MRSA Risk Lingers from ICU Room's Prior Occupant)
And, the expense of extra cleaning can be prohibitive, especially in view of the current preoccupation with hospital budgets, she said.
Concentrating already available cleaning resources on high-risk hand-touch sites may be the most cost-effective cleaning strategy other than campaigning for more cleaning hours, she concluded.
"There can be no doubt that prioritizing hand hygiene is the single most beneficial intervention in the control of MRSA and many other pathogens," she said.
However, hand-hygiene initiatives have been less successful than environmental cleaning in some studies.
"And even if everyone does wash their hands properly, the effects of exemplary hand hygiene are eroded if the environment is heavily contaminated with MRSA," Dr. Dancer added.
Dr. Dancer reported no conflicts of interest.Primary source: The Lancet Infectious DiseasesSource reference: Dancer SJ, et al "Importance of the environment in methicillin-resistant Staphylococcus aureus acquisition: the case for hospital cleaning" Lancet Infect Dis 2007; DOI: 10.1016/S1473-3099(07)70241-4.
ASTRO: Radiation Boost Lowers Breast Cancer Relapse Risk
LOS ANGELES, Oct. 31 -- Two factors increase the risk of relapse after lumpectomy for early-stage breast cancer, but a boost of radiation aimed at the tumor bed lowers that risk, researchers reported here. A high-grade invasive tumor or a high-grade ductal carcinoma in situ (DCIS) in the margins of the resected tumor both increase the risk of later relapse, according to Heather Jones, M.D., of the University of Pittsburgh, and colleagues.
But they've found that a boost of radiation aimed at the tumor bed lowers the risk of relapse even for high-risk women, Dr. Jones said at the American Society for Therapeutic Radiation and Oncology meeting.
The findings come from a secondary analysis of the European Boost-No Boost trial, a long-term randomized controlled trial that showed that an extra dose of radiation significantly reduces the risk of local relapse.
The original study, published earlier this year in the Journal of Clinical Oncology, showed that the risk of relapse was 7% after 10 years if women got the extra dose, compared with 12% without the boost.
It was confirmation that the widely used practice of boosting standard 50-Gray whole-breast radiation with 16 Gray aimed at the tumor bed actually offers a significant benefit, Dr. Jones said.
But to find out which women benefited most from the extra dose, the researchers analyzed tissue from a third of the 5,318 women in the larger randomized trial, said Dr. Jones, who became involved in the study during a fellowship at the Netherlands Cancer Institute in Amsterdam.
The study found that if the margin of the tumor was involved, the 10-year risk of relapse was 4% for women who got the boost, compared with 13% for those who did not, a difference that was significant at P=0.0001.
On the other hand, when the margin was not involved there was no significant difference in the risk of relapse, Dr. Jones said.
But more important on a multivariate analysis was the type of tumor resected and the type of tissue remaining in the margins. Specifically:
If the excised tumor proved to be high-grade invasive, the 10-year risk of relapse was 7% for those who were boosted and 19% for those who weren't, which was significant at P=0.002.
If the margin included DCIS, the relapse risk was 5% for boosted women and 17% for unboosted, which was significant at P<0.0001.
Also, women 40 or younger who were boosted had the largest absolute risk reduction -- 23.9% versus 13.5% -- which was significant at P=0.0014, Dr. Jones said.
"The boost dose reduces the effect of margin involvement and it substantially reduces the risk of local recurrence in our high-risk patients," she said.
The Netherlands Cancer Institute has changed its clinical practice to include an extra 16 Gray of radiation aimed at the tumor bed in the wake of the trial, said Harry Bartelink, Ph.D., a radiation oncologist there.
But Dr. Bartelink, the study's senior author, said he and colleagues have re-arranged the protocol to include the extra dose during the same time period as the standard 50-Gray whole-breast irradiation.
The study "confirms our existing practice, which I think is important," said Shiv Khandelwal, M.D., of the University of Virginia in Charlottesville, who was not part of the study.
Dr. Khandelwal said radiation oncologists in the U.S. tend to use a slightly lower radiation dose for the boost -- 10 Gray versus 16 in the European study -- and it may be that physicians here will now start using the higher dose.
On the other hand, he said, his practice is to use the higher dose in cases where the surgical margin around the tumor is close, defined as two millimeters or less.
One area that remains unclear is how to treat patients who undergo re-excision because the original surgical margin includes cancerous tissue, he said. If the re-excised tissue is free of cancer -- a common finding, Dr. Khandelwal said -- it's not clear if the radiation boost is needed.
The study was supported by the European Organization for Research and Treatment of Cancer. Dr. Jones said she had no conflicts.Primary source: International Journal of Radiation Oncology * Biology * PhysicsSource reference: Jones H, et al "The Impact of Boost Dose and Margins on the Local Recurrence Rate in Breast Conserving Therapy: Results From the EORTC Boost-No Boost Trial" Int J Rad Onc 2007; 69(3) Supplement S: S2.
LOS ANGELES, Oct. 31 -- Two factors increase the risk of relapse after lumpectomy for early-stage breast cancer, but a boost of radiation aimed at the tumor bed lowers that risk, researchers reported here. A high-grade invasive tumor or a high-grade ductal carcinoma in situ (DCIS) in the margins of the resected tumor both increase the risk of later relapse, according to Heather Jones, M.D., of the University of Pittsburgh, and colleagues.
But they've found that a boost of radiation aimed at the tumor bed lowers the risk of relapse even for high-risk women, Dr. Jones said at the American Society for Therapeutic Radiation and Oncology meeting.
The findings come from a secondary analysis of the European Boost-No Boost trial, a long-term randomized controlled trial that showed that an extra dose of radiation significantly reduces the risk of local relapse.
The original study, published earlier this year in the Journal of Clinical Oncology, showed that the risk of relapse was 7% after 10 years if women got the extra dose, compared with 12% without the boost.
It was confirmation that the widely used practice of boosting standard 50-Gray whole-breast radiation with 16 Gray aimed at the tumor bed actually offers a significant benefit, Dr. Jones said.
But to find out which women benefited most from the extra dose, the researchers analyzed tissue from a third of the 5,318 women in the larger randomized trial, said Dr. Jones, who became involved in the study during a fellowship at the Netherlands Cancer Institute in Amsterdam.
The study found that if the margin of the tumor was involved, the 10-year risk of relapse was 4% for women who got the boost, compared with 13% for those who did not, a difference that was significant at P=0.0001.
On the other hand, when the margin was not involved there was no significant difference in the risk of relapse, Dr. Jones said.
But more important on a multivariate analysis was the type of tumor resected and the type of tissue remaining in the margins. Specifically:
If the excised tumor proved to be high-grade invasive, the 10-year risk of relapse was 7% for those who were boosted and 19% for those who weren't, which was significant at P=0.002.
If the margin included DCIS, the relapse risk was 5% for boosted women and 17% for unboosted, which was significant at P<0.0001.
Also, women 40 or younger who were boosted had the largest absolute risk reduction -- 23.9% versus 13.5% -- which was significant at P=0.0014, Dr. Jones said.
"The boost dose reduces the effect of margin involvement and it substantially reduces the risk of local recurrence in our high-risk patients," she said.
The Netherlands Cancer Institute has changed its clinical practice to include an extra 16 Gray of radiation aimed at the tumor bed in the wake of the trial, said Harry Bartelink, Ph.D., a radiation oncologist there.
But Dr. Bartelink, the study's senior author, said he and colleagues have re-arranged the protocol to include the extra dose during the same time period as the standard 50-Gray whole-breast irradiation.
The study "confirms our existing practice, which I think is important," said Shiv Khandelwal, M.D., of the University of Virginia in Charlottesville, who was not part of the study.
Dr. Khandelwal said radiation oncologists in the U.S. tend to use a slightly lower radiation dose for the boost -- 10 Gray versus 16 in the European study -- and it may be that physicians here will now start using the higher dose.
On the other hand, he said, his practice is to use the higher dose in cases where the surgical margin around the tumor is close, defined as two millimeters or less.
One area that remains unclear is how to treat patients who undergo re-excision because the original surgical margin includes cancerous tissue, he said. If the re-excised tissue is free of cancer -- a common finding, Dr. Khandelwal said -- it's not clear if the radiation boost is needed.
The study was supported by the European Organization for Research and Treatment of Cancer. Dr. Jones said she had no conflicts.Primary source: International Journal of Radiation Oncology * Biology * PhysicsSource reference: Jones H, et al "The Impact of Boost Dose and Margins on the Local Recurrence Rate in Breast Conserving Therapy: Results From the EORTC Boost-No Boost Trial" Int J Rad Onc 2007; 69(3) Supplement S: S2.
Excess Body Fat Associated with Increased Risk for Six Cancers
WASHINGTON, Oct. 31 -- Obesity is on course to overtake tobacco as the leading risk factor for cancer in America, according to a report issued today.
Moreover, the risk for cancer increases even with modest weight gain, said Walter C. Willett, M.D., Ph.D., of the Harvard School of Public Health. He said excess body fat increased the risk for cancers of the colon, kidney, and pancreas, adenocarcinoma of the esophagus and endometrium, and breast cancer in postmenopausal women.
That was the major finding from a mega-analysis of more than 7,000 published studies conducted by a 21-member board assembled by the American Institute for Cancer Research and the World Cancer Research Fund International.
The results of the analysis, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective, were released at a press conference here.
Dr. Willett pointed out that obesity is now the second leading cause of cancer, just behind tobacco, because "obesity increases the risk of so many cancers and because two-thirds of Americans are overweight."
He and his colleagues predicted that over the next decade "obesity will become the number one risk factor for cancer" as obesity increases and the number of smokers decreases.
Dr. Willett said the finding was a call to action for clinicians, who he said should begin counseling patients about the danger of excess weight with "the first few pounds gained or first few extra inches of abdominal girth."
He faulted clinicians for failing to mention weight until patients need to lose 30 pounds or more, which he said was the wrong approach.
In addition to excess weight, Dr. Willett and colleagues said that 18 ounces of red meat per week was a safe amount but for every 1.7 additional ounces consumed per week the risk of cancer increased by 15%.
For processed meats, the panelists said it was not able to identify a safe level. "Every 1.7 ounces of processed meats consumed per day increased the risk of colorectal cancer by 21%," they said.
Dr. Willett said that alcohol was also linked to a variety of cancers and in some cases -- older women for example -- the risk of breast cancer begins to increase at levels as low as a single glass of wine per day.
How clinicians should balance the risk of breast cancer against the reported cardiovascular benefit of a daily glass of red wine is problematic, Dr. Willett admitted. But he said that folic acid consumption appeared to counterbalance the increased risk associated with alcohol.
His advice to patients who want the heart protective benefit of red wine is to take a multivitamin daily. "I believe that will offset the increased risk."
On the basis of the analysis, the panelists issued these 10 recommendations for cancer prevention:
Be lean as possible within the normal range of body weight.
Be physically active as part of everyday life.
Limit consumption of energy-dense foods. Avoid sugary drinks.
Eat mostly foods of plant origin.
Limit alcoholic drinks.
Limit consumption of salt. Avoid moldy cereals (grains) or pulses (legumes).
Aim to meet nutritional needs through diet alone.
Women of childbearing age should plan to breastfeed and children should be breastfed.
Cancer survivors should follow the recommendations for cancer prevention.
AICR supports research and educational programs focused on diet and cancer. It is a member of the World Cancer Research Fund International, which along with AICR funded the analysis. Additional source: American Institute for Cancer Research and World Cancer Research Fund InternationalSource reference: World Cancer Research Fund, American Institute for Cancer Research, "Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective" 2007.
WASHINGTON, Oct. 31 -- Obesity is on course to overtake tobacco as the leading risk factor for cancer in America, according to a report issued today.
Moreover, the risk for cancer increases even with modest weight gain, said Walter C. Willett, M.D., Ph.D., of the Harvard School of Public Health. He said excess body fat increased the risk for cancers of the colon, kidney, and pancreas, adenocarcinoma of the esophagus and endometrium, and breast cancer in postmenopausal women.
That was the major finding from a mega-analysis of more than 7,000 published studies conducted by a 21-member board assembled by the American Institute for Cancer Research and the World Cancer Research Fund International.
The results of the analysis, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective, were released at a press conference here.
Dr. Willett pointed out that obesity is now the second leading cause of cancer, just behind tobacco, because "obesity increases the risk of so many cancers and because two-thirds of Americans are overweight."
He and his colleagues predicted that over the next decade "obesity will become the number one risk factor for cancer" as obesity increases and the number of smokers decreases.
Dr. Willett said the finding was a call to action for clinicians, who he said should begin counseling patients about the danger of excess weight with "the first few pounds gained or first few extra inches of abdominal girth."
He faulted clinicians for failing to mention weight until patients need to lose 30 pounds or more, which he said was the wrong approach.
In addition to excess weight, Dr. Willett and colleagues said that 18 ounces of red meat per week was a safe amount but for every 1.7 additional ounces consumed per week the risk of cancer increased by 15%.
For processed meats, the panelists said it was not able to identify a safe level. "Every 1.7 ounces of processed meats consumed per day increased the risk of colorectal cancer by 21%," they said.
Dr. Willett said that alcohol was also linked to a variety of cancers and in some cases -- older women for example -- the risk of breast cancer begins to increase at levels as low as a single glass of wine per day.
How clinicians should balance the risk of breast cancer against the reported cardiovascular benefit of a daily glass of red wine is problematic, Dr. Willett admitted. But he said that folic acid consumption appeared to counterbalance the increased risk associated with alcohol.
His advice to patients who want the heart protective benefit of red wine is to take a multivitamin daily. "I believe that will offset the increased risk."
On the basis of the analysis, the panelists issued these 10 recommendations for cancer prevention:
Be lean as possible within the normal range of body weight.
Be physically active as part of everyday life.
Limit consumption of energy-dense foods. Avoid sugary drinks.
Eat mostly foods of plant origin.
Limit alcoholic drinks.
Limit consumption of salt. Avoid moldy cereals (grains) or pulses (legumes).
Aim to meet nutritional needs through diet alone.
Women of childbearing age should plan to breastfeed and children should be breastfed.
Cancer survivors should follow the recommendations for cancer prevention.
AICR supports research and educational programs focused on diet and cancer. It is a member of the World Cancer Research Fund International, which along with AICR funded the analysis. Additional source: American Institute for Cancer Research and World Cancer Research Fund InternationalSource reference: World Cancer Research Fund, American Institute for Cancer Research, "Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective" 2007.
Higher Resting Heart Rate Linked to Diabetes and Mortality in Older Age
October 31, 2007 — Higher resting heart rate (HR) was associated with diabetes and mortality in older age, according to the results of a study reported in the October 24 Online First issue of Diabetes Care.
"Given that estimates of autonomic function and fitness are associated with the development of insulin resistance and hyperglycemia in population studies and that heart rate is correlated with these physiologic measures, it is biologically plausible that higher heart rate is associated with the development of diabetes," write Mercedes Carnethon, PhD, from the Feinberg School of Medicine, Northwestern University in Chicago, Illinois, and colleagues. "In a sample of young and middle-aged adults, we tested the hypothesis that a faster resting heart rate was associated with a greater likelihood of experiencing diabetes-related morbidity or mortality in older age (after age 65 years)."
In the Chicago Heart Association Detection Project in Industry Study, resting HR was measured at baseline, from 1967 to 1973. Using Medicare billing records for 14,992 participants aged 35 to 64 years who were free from diabetes at baseline, the investigators identified diabetes-related hospital claims and non–hospital-based diabetes expenses from 1992 through 2002. They also determined diabetes-related mortality from 1984 to 2002 using National Death Index codes 250.XX (International Classification of Diseases [ICD]-8 and -9) and E10–E14 (ICD-10).
Diabetes-related hospital claims occurred in 1877 participants after age 65 years, and 410 participants had some mention of diabetes on their death certificate. For every 12-bpm higher baseline HR, the odds of having a diabetes-related claim was approximately 10% higher (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.05 - 1.16), after adjustment for demographic characteristics, cigarette smoking, and years of Medicare eligibility.
This association became nonsignificant after adjustment for body mass index (BMI) and postload glucose levels at baseline. In adults aged 35 to 49 years at baseline, higher HR was associated with diabetes-related mortality after adjustment for postload glucose levels and BMI (OR, 1.21; 95% CI, 1.03 - 1.41).
"Higher resting HR is associated with diabetes claims and mortality in older age, and is only due in part to BMI and concurrently-measured glucose," the study authors write.
Limitations of the study include measured glucose levels lower than would be obtained with current standard measurement techniques, possible underestimate of the number of participants with fasting glucose levels of more than 11.1 mmol/L who had undiagnosed diabetes, diagnosis of diabetes at follow-up based on Medicare claims data, findings only generalizable to adults who live to older age, reliance on hospital visit diagnosis codes to identify diabetes, inability to evaluate the role of changes in covariates with time on the association between HR and diabetes, and no measurement of physical activity available for statistical adjustment.
"In our study of a large sample of middle-aged adults, baseline heart rate (measured up to 35 years before) was associated with diabetes diagnoses and mortality in older age," the study authors conclude. "Our findings provide further evidence that higher heart rate is associated with adverse morbidity and mortality from a number of causes including diabetes."
The National Heart, Lung, and Blood Institute funded this study.
Diabetes Care. Published online October 24, 2007.
October 31, 2007 — Higher resting heart rate (HR) was associated with diabetes and mortality in older age, according to the results of a study reported in the October 24 Online First issue of Diabetes Care.
"Given that estimates of autonomic function and fitness are associated with the development of insulin resistance and hyperglycemia in population studies and that heart rate is correlated with these physiologic measures, it is biologically plausible that higher heart rate is associated with the development of diabetes," write Mercedes Carnethon, PhD, from the Feinberg School of Medicine, Northwestern University in Chicago, Illinois, and colleagues. "In a sample of young and middle-aged adults, we tested the hypothesis that a faster resting heart rate was associated with a greater likelihood of experiencing diabetes-related morbidity or mortality in older age (after age 65 years)."
In the Chicago Heart Association Detection Project in Industry Study, resting HR was measured at baseline, from 1967 to 1973. Using Medicare billing records for 14,992 participants aged 35 to 64 years who were free from diabetes at baseline, the investigators identified diabetes-related hospital claims and non–hospital-based diabetes expenses from 1992 through 2002. They also determined diabetes-related mortality from 1984 to 2002 using National Death Index codes 250.XX (International Classification of Diseases [ICD]-8 and -9) and E10–E14 (ICD-10).
Diabetes-related hospital claims occurred in 1877 participants after age 65 years, and 410 participants had some mention of diabetes on their death certificate. For every 12-bpm higher baseline HR, the odds of having a diabetes-related claim was approximately 10% higher (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.05 - 1.16), after adjustment for demographic characteristics, cigarette smoking, and years of Medicare eligibility.
This association became nonsignificant after adjustment for body mass index (BMI) and postload glucose levels at baseline. In adults aged 35 to 49 years at baseline, higher HR was associated with diabetes-related mortality after adjustment for postload glucose levels and BMI (OR, 1.21; 95% CI, 1.03 - 1.41).
"Higher resting HR is associated with diabetes claims and mortality in older age, and is only due in part to BMI and concurrently-measured glucose," the study authors write.
Limitations of the study include measured glucose levels lower than would be obtained with current standard measurement techniques, possible underestimate of the number of participants with fasting glucose levels of more than 11.1 mmol/L who had undiagnosed diabetes, diagnosis of diabetes at follow-up based on Medicare claims data, findings only generalizable to adults who live to older age, reliance on hospital visit diagnosis codes to identify diabetes, inability to evaluate the role of changes in covariates with time on the association between HR and diabetes, and no measurement of physical activity available for statistical adjustment.
"In our study of a large sample of middle-aged adults, baseline heart rate (measured up to 35 years before) was associated with diabetes diagnoses and mortality in older age," the study authors conclude. "Our findings provide further evidence that higher heart rate is associated with adverse morbidity and mortality from a number of causes including diabetes."
The National Heart, Lung, and Blood Institute funded this study.
Diabetes Care. Published online October 24, 2007.
Cancer Risk Increased by Excess Body Fat, Red and Processed Meats, and Alcohol
Roxanne Nelson
October 31, 2007 — There is convincing evidence that excess weight and obesity can increase the risk for 6 different cancers, including those of the colon, kidney, and pancreas, according to a report issued by the American Institute for Cancer Research (AICR) and the World Cancer Research Fund. The second expert report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective, considered to be the most comprehensive scientific analysis of cancer prevention and causation ever undertaken, also reported that there is convincing evidence that the consumption of alcohol, red meat, and processed meat elevates cancer risk.
"The most striking finding in the report is that excess body fat increases risk for numerous cancers. That is why body weight is the focus of our first recommendation," expert panel member W. Phillip T. James, MD, DSc, from the International Obesity Task Force, in London, United Kingdom, told journalists.
The document, which was written by an international expert panel, reviewed 7000 research studies over a 5-year period and classified the accumulated evidence for specific diet-cancer links. It is the second one to be published in the past 10 years and provides the most inclusive evidence to date linking cancer risk to diet, physical activity, and weight.
Although cancer is considered to be a disease of genes that are vulnerable to mutation, evidence indicates that only a small number of cancers are inherited, write the experts. Instead, it appears that environmental factors are the most important, and these can often be modified with a resultant reduction in risk. These factors include tobacco use, infectious agents, radiation, industrial chemicals, pollution, medications, nutrition, physical activity, and body composition.
One of the strongest findings in the report was that excess body fat is associated with an increased cancer risk and can increase the risk for 6 different types of the disease: colon, kidney, pancreas, adenocarcinoma of the esophagus and endometrium, and postmenopausal breast cancer. They also reported that alcohol is convincingly linked to a number of cancers, including those of the colon, breast, esophagus, and mouth, larynx and pharynx.
To combat excess weight and maintain a healthy body-mass index, the experts recommend limiting the intake of energy-dense foods, particularly those that are highly processed. These products tend to be high in sugar and fat and low in fiber. They also advise increasing physical activity and getting some exercise for at least 30 minutes a day. Physical activity not only helps individuals keep excess weight off, but it helps reduce the risk for cancer in its own right.
Evidence has also increased since the first report, issued in 1997, which links the consumption of red meat (beef, pork, and lamb) to colorectal cancer. The panel's recommendation is to limit the consumption of red meat to 18 ounces per week because, beyond this amount, evidence shows that for every additional 1.7 ounces of red meat consumed per day, the risk for cancer rises by 15%.
Their recommendation concerning the consumption of processed meats is even more stringent. Processed meats, such as bacon, ham, sausage, and lunch meat, should be avoided entirely; the panel was unable to find a level at which the consumption of these products can be reliably considered completely safe. For every 1.7 ounces of processed meat consumed per day, the risk for colorectal cancer rises by 21%.
Evidence also indicates that the majority of diets that are protective against cancer are made up primarily of foods of plant origin. Higher consumption of several plant foods might offer protection against cancers of various sites.
"We are recommending 5 servings or more of vegetables and fruit daily because, like physical activity, they pack a double whammy against cancer. Probable evidence indicates that they help reduce cancer risk on their own and, as low energy-dense foods, they help maintain a healthy weight, which the evidence shows has a big influence on cancer risk," Dr. James said during a press conference.
The panel also looked at factors that included birth weight, childbearing, breast-feeding, and adult height and found that they all can influence the risk for cancer. High birth weight is associated with an increased risk for premenopausal breast cancer, which is likely linked to excess body fat and the resultant hormonal changes.
Exclusive breast-feeding appears to offer protection for both mother and child. It can help lower the risk for breast cancer in women and also lower the risk of becoming overweight and obese in children.
"The evidence is uniformly strong on breast-feeding, and the fact that it offers cancer protection to both mothers and their children is why we made breast-feeding 1 of our 10 recommendations to prevent cancer," said expert panel member Walter J. Willett, MD, PhD, from the Harvard School of Public Health, in Boston, Massachusetts, at a press conference.
The panel also found an association between adult height and cancer risk. Tall adults appear to have a higher risk of colorectal and postmenopausal breast cancer, and there is some evidence linking tallness to an increased risk for ovarian, pancreatic, and premenopausal cancer.
The recommendations made in this report are applicable to cancer survivors when appropriate and unless otherwise advised by their healthcare practitioner. Because increasing numbers of cancer patients survive their disease and live long enough to develop new primary cancers or other chronic diseases, the expert panel believes that these recommendations can help reduce the risk.
Recommendations for Cancer Prevention
1. Be as lean as possible within the normal range of body weight.2. Be physically active as part of everyday life.3. Limit consumption of energy-dense foods; avoid sugary drinks.4. Eat mostly foods of plant origin.5. Limit intake of red meat; avoid processed meat.6. Limit alcoholic drinks.7. Limit consumption of salt; avoid moldy cereals (grains) or pulses (legumes).8. Aim to meet nutritional needs through diet alone.
Special Population Recommendations
9. Mothers should breast-feed; children should be breast-fed.10. Cancer survivors should follow the recommendations for cancer prevention.
World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR; 2007.
Roxanne Nelson
October 31, 2007 — There is convincing evidence that excess weight and obesity can increase the risk for 6 different cancers, including those of the colon, kidney, and pancreas, according to a report issued by the American Institute for Cancer Research (AICR) and the World Cancer Research Fund. The second expert report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective, considered to be the most comprehensive scientific analysis of cancer prevention and causation ever undertaken, also reported that there is convincing evidence that the consumption of alcohol, red meat, and processed meat elevates cancer risk.
"The most striking finding in the report is that excess body fat increases risk for numerous cancers. That is why body weight is the focus of our first recommendation," expert panel member W. Phillip T. James, MD, DSc, from the International Obesity Task Force, in London, United Kingdom, told journalists.
The document, which was written by an international expert panel, reviewed 7000 research studies over a 5-year period and classified the accumulated evidence for specific diet-cancer links. It is the second one to be published in the past 10 years and provides the most inclusive evidence to date linking cancer risk to diet, physical activity, and weight.
Although cancer is considered to be a disease of genes that are vulnerable to mutation, evidence indicates that only a small number of cancers are inherited, write the experts. Instead, it appears that environmental factors are the most important, and these can often be modified with a resultant reduction in risk. These factors include tobacco use, infectious agents, radiation, industrial chemicals, pollution, medications, nutrition, physical activity, and body composition.
One of the strongest findings in the report was that excess body fat is associated with an increased cancer risk and can increase the risk for 6 different types of the disease: colon, kidney, pancreas, adenocarcinoma of the esophagus and endometrium, and postmenopausal breast cancer. They also reported that alcohol is convincingly linked to a number of cancers, including those of the colon, breast, esophagus, and mouth, larynx and pharynx.
To combat excess weight and maintain a healthy body-mass index, the experts recommend limiting the intake of energy-dense foods, particularly those that are highly processed. These products tend to be high in sugar and fat and low in fiber. They also advise increasing physical activity and getting some exercise for at least 30 minutes a day. Physical activity not only helps individuals keep excess weight off, but it helps reduce the risk for cancer in its own right.
Evidence has also increased since the first report, issued in 1997, which links the consumption of red meat (beef, pork, and lamb) to colorectal cancer. The panel's recommendation is to limit the consumption of red meat to 18 ounces per week because, beyond this amount, evidence shows that for every additional 1.7 ounces of red meat consumed per day, the risk for cancer rises by 15%.
Their recommendation concerning the consumption of processed meats is even more stringent. Processed meats, such as bacon, ham, sausage, and lunch meat, should be avoided entirely; the panel was unable to find a level at which the consumption of these products can be reliably considered completely safe. For every 1.7 ounces of processed meat consumed per day, the risk for colorectal cancer rises by 21%.
Evidence also indicates that the majority of diets that are protective against cancer are made up primarily of foods of plant origin. Higher consumption of several plant foods might offer protection against cancers of various sites.
"We are recommending 5 servings or more of vegetables and fruit daily because, like physical activity, they pack a double whammy against cancer. Probable evidence indicates that they help reduce cancer risk on their own and, as low energy-dense foods, they help maintain a healthy weight, which the evidence shows has a big influence on cancer risk," Dr. James said during a press conference.
The panel also looked at factors that included birth weight, childbearing, breast-feeding, and adult height and found that they all can influence the risk for cancer. High birth weight is associated with an increased risk for premenopausal breast cancer, which is likely linked to excess body fat and the resultant hormonal changes.
Exclusive breast-feeding appears to offer protection for both mother and child. It can help lower the risk for breast cancer in women and also lower the risk of becoming overweight and obese in children.
"The evidence is uniformly strong on breast-feeding, and the fact that it offers cancer protection to both mothers and their children is why we made breast-feeding 1 of our 10 recommendations to prevent cancer," said expert panel member Walter J. Willett, MD, PhD, from the Harvard School of Public Health, in Boston, Massachusetts, at a press conference.
The panel also found an association between adult height and cancer risk. Tall adults appear to have a higher risk of colorectal and postmenopausal breast cancer, and there is some evidence linking tallness to an increased risk for ovarian, pancreatic, and premenopausal cancer.
The recommendations made in this report are applicable to cancer survivors when appropriate and unless otherwise advised by their healthcare practitioner. Because increasing numbers of cancer patients survive their disease and live long enough to develop new primary cancers or other chronic diseases, the expert panel believes that these recommendations can help reduce the risk.
Recommendations for Cancer Prevention
1. Be as lean as possible within the normal range of body weight.2. Be physically active as part of everyday life.3. Limit consumption of energy-dense foods; avoid sugary drinks.4. Eat mostly foods of plant origin.5. Limit intake of red meat; avoid processed meat.6. Limit alcoholic drinks.7. Limit consumption of salt; avoid moldy cereals (grains) or pulses (legumes).8. Aim to meet nutritional needs through diet alone.
Special Population Recommendations
9. Mothers should breast-feed; children should be breast-fed.10. Cancer survivors should follow the recommendations for cancer prevention.
World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR; 2007.
My Diet Strategy? Controlled Indulgence
By JANE E. BRODY
Most people who know me well know that I love ice cream. It has been my favorite comfort food since early childhood, when the Good Humor truck came around daily and a local luncheonette sold double cones for 25 cents. But a new friend was shocked to learn that I routinely keep about six half-gallons of ice cream in my freezer.
They are not all for me. A few are flavors favored by my twin grandsons, who spend two afternoons a week at my house. Still, quite a few have my name on them, and I don’t hesitate to indulge almost nightly.
Imposing Self-Control
You see, despite my well-known interest in healthful eating, I don’t believe in deprivation. I learned long ago, when I struggled unsuccessfully for more than a year to lose 35 pounds, that deprivation feeds desire and can lead to overindulgence at the first opportunity.
And so I adopted a philosophy that I call controlled indulgence. In the two years it took me to return to a reasonable weight for my 5-foot frame, I allowed myself one small treat each day — perhaps two cookies, a thin slice of cake or pie or a few tablespoons of ice cream. The strategy worked, and I continued to use it in the decades of weight maintenance that followed.
For as long as my twin sons lived at home, rather than buy commercial cakes and cookies, I baked quick breads and muffins that were relatively low in sugar and fat and loaded with healthful ingredients like whole wheat flour, bran, wheat germ, fruits and vegetables. They served as the family’s desserts and between-meal snacks. I took some to work with me every day to enjoy when the coffee cart appeared in midafternoon.
But back to the ice cream in the freezer. My approach starts with smart selection. I read the nutrition label; the only ice cream I buy provides a maximum of 150 calories a serving, and usually less, 100 to 130. Most are the slow-churned reduced-fat flavors, and some are frozen yogurt. But none are fat free or sugar free, which to me tastes ersatz.
Equally important, of course, is how much to eat at any one time. One serving. Do you know what a serving of ice cream is? It is half a cup. I bought some half-cup containers and measure out my daily indulgence. And I made a rule for myself. If I start eating more than that half cup, all the ice cream has to go. Because I would rather have it around when I want it, I stick to the half cup.
Some people I know say they could never do that. If the ice cream was in the house, they would eat far too much of it. They say they are safer buying a cone when an irresistible urge strikes. But I resent spending $2.50 for a cone when I can buy a half gallon (all right, 56 ounces) for $2.99.
Ice cream is not my only passion.
Chocolate, that is, dark chocolate, runs a close second. There was a time when a box of chocolates could sit in my house for months and I would never eat even one piece. Those days, it seems, are gone forever. I blame menopause for my current cravings for chocolate. And I keep quite a lot of it around, especially chocolate-covered almonds and Trader Joe’s minipretzels smothered in dark chocolate. Again, the house rule is portion control. Four almonds or two pretzels a day or out they go.
Strategic Rationing
Having heard too many stories about children whose parents forbid them to have any treats who then sneak and hoard the forbidden fruit at every opportunity, I chose a different approach with my sons. Nothing was forbidden, but some foods were just not readily available.
We kept no candy, soda, chips or sugary cereals in the house. But the boys could order soda when we dined out and eat any cereal they wanted when they spent the night at a friend’s house. And every Saturday, we gave them money to buy a bar of any candy they wanted.
At first, they nursed that candy bar for hours. But after a few months, the candy was nowhere to be seen. Without a word from any adult, they had decided to use the money to buy knishes instead.
What amazes me more than anything is that at age 38, my sons still have no interest in candy; do not drink soda; rarely have cake, pie or cookies; and have no trouble keeping their hands out of a bowl of chips. As with their mother, their main treat is ice cream, which at least has some redeeming nutritional value.
Overcoming Temptation
The philosophy of controlled indulgence goes beyond treats. I apply it across the board, in all occasions when I might otherwise be tempted to overindulge.
For example, at events where food is served buffet style, I start by surveying the entire selection before I get in line to fill my plate. That way, I don’t take everything that is offered. Instead, I end up only with foods I am most likely to enjoy without straying too far from my dietary goals. When salad is among the offerings, I pile it on the plate first, leaving less room for some of the more caloric selections.
Because fruit is usually among the dessert offerings, I eat that first so I have less room and desire for higher-calorie choices.
Sit-down dinners can be more of a challenge. They usually start with salad, and I am not shy about requesting dressing on the side and a second serving if one might be available. I tend to eat all of everything I like, including dessert, but I do not waste calories on food that is not very good. I routinely scrape off sauces, remove the skin from chicken and skip stuffings (unless fellow diners say it’s scrumptious).
I do not count calories or make lists of everything I eat each day. In fact, I have no idea how many calories I consume on a typical day. I eat for enjoyment — foods that I like, most of which happen to be good for me, and in quantities that I find satisfying.
Rather than counting calories, I monitor my weight. I step on the scale every morning before breakfast. If I start to gain, I cut back a little on portions. But consistent with my philosophy of limitation, not deprivation, I don’t cut out my treats.
By JANE E. BRODY
Most people who know me well know that I love ice cream. It has been my favorite comfort food since early childhood, when the Good Humor truck came around daily and a local luncheonette sold double cones for 25 cents. But a new friend was shocked to learn that I routinely keep about six half-gallons of ice cream in my freezer.
They are not all for me. A few are flavors favored by my twin grandsons, who spend two afternoons a week at my house. Still, quite a few have my name on them, and I don’t hesitate to indulge almost nightly.
Imposing Self-Control
You see, despite my well-known interest in healthful eating, I don’t believe in deprivation. I learned long ago, when I struggled unsuccessfully for more than a year to lose 35 pounds, that deprivation feeds desire and can lead to overindulgence at the first opportunity.
And so I adopted a philosophy that I call controlled indulgence. In the two years it took me to return to a reasonable weight for my 5-foot frame, I allowed myself one small treat each day — perhaps two cookies, a thin slice of cake or pie or a few tablespoons of ice cream. The strategy worked, and I continued to use it in the decades of weight maintenance that followed.
For as long as my twin sons lived at home, rather than buy commercial cakes and cookies, I baked quick breads and muffins that were relatively low in sugar and fat and loaded with healthful ingredients like whole wheat flour, bran, wheat germ, fruits and vegetables. They served as the family’s desserts and between-meal snacks. I took some to work with me every day to enjoy when the coffee cart appeared in midafternoon.
But back to the ice cream in the freezer. My approach starts with smart selection. I read the nutrition label; the only ice cream I buy provides a maximum of 150 calories a serving, and usually less, 100 to 130. Most are the slow-churned reduced-fat flavors, and some are frozen yogurt. But none are fat free or sugar free, which to me tastes ersatz.
Equally important, of course, is how much to eat at any one time. One serving. Do you know what a serving of ice cream is? It is half a cup. I bought some half-cup containers and measure out my daily indulgence. And I made a rule for myself. If I start eating more than that half cup, all the ice cream has to go. Because I would rather have it around when I want it, I stick to the half cup.
Some people I know say they could never do that. If the ice cream was in the house, they would eat far too much of it. They say they are safer buying a cone when an irresistible urge strikes. But I resent spending $2.50 for a cone when I can buy a half gallon (all right, 56 ounces) for $2.99.
Ice cream is not my only passion.
Chocolate, that is, dark chocolate, runs a close second. There was a time when a box of chocolates could sit in my house for months and I would never eat even one piece. Those days, it seems, are gone forever. I blame menopause for my current cravings for chocolate. And I keep quite a lot of it around, especially chocolate-covered almonds and Trader Joe’s minipretzels smothered in dark chocolate. Again, the house rule is portion control. Four almonds or two pretzels a day or out they go.
Strategic Rationing
Having heard too many stories about children whose parents forbid them to have any treats who then sneak and hoard the forbidden fruit at every opportunity, I chose a different approach with my sons. Nothing was forbidden, but some foods were just not readily available.
We kept no candy, soda, chips or sugary cereals in the house. But the boys could order soda when we dined out and eat any cereal they wanted when they spent the night at a friend’s house. And every Saturday, we gave them money to buy a bar of any candy they wanted.
At first, they nursed that candy bar for hours. But after a few months, the candy was nowhere to be seen. Without a word from any adult, they had decided to use the money to buy knishes instead.
What amazes me more than anything is that at age 38, my sons still have no interest in candy; do not drink soda; rarely have cake, pie or cookies; and have no trouble keeping their hands out of a bowl of chips. As with their mother, their main treat is ice cream, which at least has some redeeming nutritional value.
Overcoming Temptation
The philosophy of controlled indulgence goes beyond treats. I apply it across the board, in all occasions when I might otherwise be tempted to overindulge.
For example, at events where food is served buffet style, I start by surveying the entire selection before I get in line to fill my plate. That way, I don’t take everything that is offered. Instead, I end up only with foods I am most likely to enjoy without straying too far from my dietary goals. When salad is among the offerings, I pile it on the plate first, leaving less room for some of the more caloric selections.
Because fruit is usually among the dessert offerings, I eat that first so I have less room and desire for higher-calorie choices.
Sit-down dinners can be more of a challenge. They usually start with salad, and I am not shy about requesting dressing on the side and a second serving if one might be available. I tend to eat all of everything I like, including dessert, but I do not waste calories on food that is not very good. I routinely scrape off sauces, remove the skin from chicken and skip stuffings (unless fellow diners say it’s scrumptious).
I do not count calories or make lists of everything I eat each day. In fact, I have no idea how many calories I consume on a typical day. I eat for enjoyment — foods that I like, most of which happen to be good for me, and in quantities that I find satisfying.
Rather than counting calories, I monitor my weight. I step on the scale every morning before breakfast. If I start to gain, I cut back a little on portions. But consistent with my philosophy of limitation, not deprivation, I don’t cut out my treats.
New Guidelines on Venous Thromboembolism in Cancer Patients
The American Society of Clinical Oncology has released new guidelines for prevention and treatment of venous thromboembolism in cancer patients. The guidelines come in the face of a 35% increase in cancer-associated VTE from 1995 to 2002.
Published early online in the Journal of Clinical Oncology, the guidelines recommend the following:
All hospitalized cancer patients should be considered for prophylaxis against VTE, in the absence of bleeding or other contraindications.
Prophylaxis is not recommended for ambulatory patients unless they are under treatment for multiple myeloma with thalidomide or lenalidomide.
Patients undergoing major surgery should be considered for prophylaxis, as well as those undergoing minor surgical procedures lasting longer than 30 minutes. (Prophylaxis should continue for roughly a week, and in high-risk patients after major surgery, it should continue for up to 4 weeks.)
Low-molecular-weight heparin is the preferred agent for treating VTE.
The American Society of Clinical Oncology has released new guidelines for prevention and treatment of venous thromboembolism in cancer patients. The guidelines come in the face of a 35% increase in cancer-associated VTE from 1995 to 2002.
Published early online in the Journal of Clinical Oncology, the guidelines recommend the following:
All hospitalized cancer patients should be considered for prophylaxis against VTE, in the absence of bleeding or other contraindications.
Prophylaxis is not recommended for ambulatory patients unless they are under treatment for multiple myeloma with thalidomide or lenalidomide.
Patients undergoing major surgery should be considered for prophylaxis, as well as those undergoing minor surgical procedures lasting longer than 30 minutes. (Prophylaxis should continue for roughly a week, and in high-risk patients after major surgery, it should continue for up to 4 weeks.)
Low-molecular-weight heparin is the preferred agent for treating VTE.
Better Prostate Cancer Survival for Men Taking Statins
By Ed EdelsonHealthDay ReporterWed Oct 31, 7:00 PM ET
WEDNESDAY, Oct. 31 (HealthDay News) -- Men who were taking statins to lower their cholesterol had a 10 percent greater chance of being cured of prostate cancer by radiation therapy 10 years after diagnosis, a new study finds.
It's an "intriguing and very interesting finding," but falls short of supporting statin use for all prostate cancer patients, said study author Dr. Michael J. Zelefsky, a professor of radiation oncology at Memorial Sloan-Kettering Cancer Center in New York City. He was to deliver the results Wednesday at the American Society for Therapeutic Radiology and Oncology annual meeting, in Los Angeles.
"But I would encourage men to see their internist and get on the medications if their blood cholesterol warranted it," he said.
Zelefsky reported on 871 men given radiation therapy for prostate cancer between 1995 and 2000. The five-year relapse-free survival rate for the 168 men taking statins was 91 percent while the 10-year survival rate was 76 percent. That compares to 81 percent and 66 percent, respectively, for those not taking the drugs.
"There have been some reports of a lower risk of developing prostate cancer for those men who have been on statins," Zelefsky said, but the possible mechanisms by which the drugs might help prevent the disease or cure it are unknown.
"There was a suggestion made of a possible added benefit by an interaction between the drug and radiation," he said. "Or does it have its own independent effect? That is possible as well."
Zelefsky added that this study, and others suggesting a beneficial effect of statins on prostate cancer, "give fuel to stimulate what is the only way to absolutely corroborate such an effect, in a randomized, controlled trial."
Dr. Eric Horwitz, clinical director of radiation oncology at the Fox Chase Cancer Center in Philadelphia, said he agreed with Zelefsky's call for a tightly monitored clinical trial. "There has been great success in running these large tests, and I'm sure it can be done."
As it is, many men diagnosed with prostate cancer are already taking statins, and there is no reason for them to stop, Horwitz said. "This report is reassuring because of the overlap," he noted.
Two recent reports have linked statin use with a lower risk of developing prostate cancer. One study, from the University of Alabama, Birmingham, found a decline in prostate cancer death rates that was most notable among white men who used statins.
Another study, from Duke University Medical Center, found lower blood levels of prostate-specific antigen, a potential marker of the cancer, among men taking statins.
A study on statin use in prostate cancer prevention or treatment should center on men at higher risk, Zelefsky said -- "Older men with a family history."
There is "no significant downside" to statin use in such studies because the drugs have a low rate of adverse side effects, he said.
More information
For more on prostate cancer, visit the U.S. National Cancer Institute.
By Ed EdelsonHealthDay ReporterWed Oct 31, 7:00 PM ET
WEDNESDAY, Oct. 31 (HealthDay News) -- Men who were taking statins to lower their cholesterol had a 10 percent greater chance of being cured of prostate cancer by radiation therapy 10 years after diagnosis, a new study finds.
It's an "intriguing and very interesting finding," but falls short of supporting statin use for all prostate cancer patients, said study author Dr. Michael J. Zelefsky, a professor of radiation oncology at Memorial Sloan-Kettering Cancer Center in New York City. He was to deliver the results Wednesday at the American Society for Therapeutic Radiology and Oncology annual meeting, in Los Angeles.
"But I would encourage men to see their internist and get on the medications if their blood cholesterol warranted it," he said.
Zelefsky reported on 871 men given radiation therapy for prostate cancer between 1995 and 2000. The five-year relapse-free survival rate for the 168 men taking statins was 91 percent while the 10-year survival rate was 76 percent. That compares to 81 percent and 66 percent, respectively, for those not taking the drugs.
"There have been some reports of a lower risk of developing prostate cancer for those men who have been on statins," Zelefsky said, but the possible mechanisms by which the drugs might help prevent the disease or cure it are unknown.
"There was a suggestion made of a possible added benefit by an interaction between the drug and radiation," he said. "Or does it have its own independent effect? That is possible as well."
Zelefsky added that this study, and others suggesting a beneficial effect of statins on prostate cancer, "give fuel to stimulate what is the only way to absolutely corroborate such an effect, in a randomized, controlled trial."
Dr. Eric Horwitz, clinical director of radiation oncology at the Fox Chase Cancer Center in Philadelphia, said he agreed with Zelefsky's call for a tightly monitored clinical trial. "There has been great success in running these large tests, and I'm sure it can be done."
As it is, many men diagnosed with prostate cancer are already taking statins, and there is no reason for them to stop, Horwitz said. "This report is reassuring because of the overlap," he noted.
Two recent reports have linked statin use with a lower risk of developing prostate cancer. One study, from the University of Alabama, Birmingham, found a decline in prostate cancer death rates that was most notable among white men who used statins.
Another study, from Duke University Medical Center, found lower blood levels of prostate-specific antigen, a potential marker of the cancer, among men taking statins.
A study on statin use in prostate cancer prevention or treatment should center on men at higher risk, Zelefsky said -- "Older men with a family history."
There is "no significant downside" to statin use in such studies because the drugs have a low rate of adverse side effects, he said.
More information
For more on prostate cancer, visit the U.S. National Cancer Institute.
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