Men okay with prostate cancer surveillance: study
Fri Sep 28, 3:34 PM ET
In men with early or "localized" prostate cancer, the strategy of active surveillance of their cancer does not appear to increase levels of psychological stress any more than undergoing immediate treatment does, according to UK researchers.
With active surveillance, or "watchful waiting," patients with early prostate tumors are monitored regularly and only treated if their cancer progresses.
"Our study found that men on active surveillance were no more likely to have anxiety and depression than those who were receiving, or had received, immediate treatment," study chief Dr. Katriina L. Whitaker told Reuters Health. This supports the acceptability of active surveillance as an approach for managing localized prostate cancer.
The paper was published in the September issue of BJU International. Dr. Whitaker's last name at the time was Burnet.
Although studies suggest that many men with localized prostate cancer may not require radical treatment, like surgery, a consequence of active surveillance may be increased psychological stress, Whitaker of University College London and colleagues note.
To determine if this is the case, they followed 329 men with localized disease. One hundred were on active surveillance, 81 were currently receiving radical treatment and 148 had previously received radical radiation therapy.
Overall, 16 percent met criteria for anxiety and 6 percent met criteria for depression. Analysis showed that higher anxiety scores were significantly associated with being younger and with a longer interval since diagnosis. Depression was also significantly associated with a longer interval since diagnosis.
However, anxiety and depression were not significantly associated with management by active surveillance.
The researchers point out that other measures of coping and quality of life might also be important. However, they conclude that close monitoring "was not associated with greater psychological distress than more immediate treatment for prostate cancer."
SOURCE: BJU International, September 2007.
Saturday, September 29, 2007
Gene mutation tied to early-onset Parkinson disease
By Will Boggs, MDFri Sep 28, 3:36 PM ET
People with a certain gene mutation are more likely to get Parkinson's disease early -- before the age of 50 -- compared to those without the gene abnormality, according to a new study.
Dr. Lorraine N. Clark, from Columbia University, New York, and colleagues analyzed the genes of 278 people with Parkinson's disease and 179 people without the disease.
They report that 14 percent of the people with Parkinson's disease carried mutations in the glucocerebrosidase (GBA) gene compared to only five percent of people without the disease.
The gene abnormality was found in 22 percent of people who were diagnosed with Parkinson's disease before age 50 compared to 10 percent of the people with disease onset after age 50.
"Our results confirm that GBA mutations are risk factors for Parkinson's disease and may lead to getting the disease at a younger age," Clark said in a statement. "We found those people with GBA mutations developed Parkinson's disease nearly two years earlier than people without the gene abnormality."
The researchers also looked at how Jewish ancestry affected the likelihood of getting Parkinson's disease at an earlier age since some studies have found people with Jewish ancestry are more likely to have GBA mutations.
Of those with Parkinson's disease, Clark's team found the gene abnormality in 17 percent of subjects with Jewish ancestry compared to only eight percent of those without Jewish ancestry, suggesting that it may be an important risk factor in people with Jewish ancestry.
SOURCE: Neurology September 18, 2007.
By Will Boggs, MDFri Sep 28, 3:36 PM ET
People with a certain gene mutation are more likely to get Parkinson's disease early -- before the age of 50 -- compared to those without the gene abnormality, according to a new study.
Dr. Lorraine N. Clark, from Columbia University, New York, and colleagues analyzed the genes of 278 people with Parkinson's disease and 179 people without the disease.
They report that 14 percent of the people with Parkinson's disease carried mutations in the glucocerebrosidase (GBA) gene compared to only five percent of people without the disease.
The gene abnormality was found in 22 percent of people who were diagnosed with Parkinson's disease before age 50 compared to 10 percent of the people with disease onset after age 50.
"Our results confirm that GBA mutations are risk factors for Parkinson's disease and may lead to getting the disease at a younger age," Clark said in a statement. "We found those people with GBA mutations developed Parkinson's disease nearly two years earlier than people without the gene abnormality."
The researchers also looked at how Jewish ancestry affected the likelihood of getting Parkinson's disease at an earlier age since some studies have found people with Jewish ancestry are more likely to have GBA mutations.
Of those with Parkinson's disease, Clark's team found the gene abnormality in 17 percent of subjects with Jewish ancestry compared to only eight percent of those without Jewish ancestry, suggesting that it may be an important risk factor in people with Jewish ancestry.
SOURCE: Neurology September 18, 2007.
Friday, September 28, 2007
Five commonly misdiagnosed diseases
By Elizabeth CohenCNN
ATLANTA, Georgia -- The celebrity was John Ritter.
The actor died in 2003 of an aortic dissection -- a tearing of the major artery that comes out of the heart. His widow later settled a wrongful death lawsuit against a California hospital, alleging his condition had been misdiagnosed "at least twice."
Experts who study malpractice cases and autopsy reports say certain diseases are misdiagnosed over and over again. It's worth knowing what they are so you won't be a victim.
1. Aortic dissection: Sometimes aortic dissections are easy to diagnose -- a patient feels a distinct tearing sensation in his or her chest. But other times they're pretty easy to miss because the symptoms could point to other diseases, says Dr. Robert Bonow, past president of the American Heart Association. "Sometimes it feels like heartburn," he says.
2. Cancer: In a Harvard study of malpractice claims in the U.S., cancer was far and away the most misdiagnosed illness, primarily breast and colorectal. Study authors attributed this to doctors failing to stick to cancer screening guidelines.
3. Clogged arteries: Sometimes doctors tell patients they're short of breath because they're out of shape, when it's actually coronary artery disease, says Bonow, who's also the chief of cardiology at Northwestern Medical School.
4. Heart attack: Sound strange? How could a doctor miss a heart attack? Bonow says the big and obvious attack -- the one where someone clutches his or her chest and falls to the floor, the one Bonow calls "the Hollywood heart attack" -- isn't always so clear. Sometimes the only signs of a heart attack are a sense of fullness in the chest, nausea and a general sense of not feeling well.
5. Infection: In the Harvard study, infection followed cancer as the most misdiagnosed condition.
So how can you keep yourself from becoming a victim of misdiagnosis?
1. Ask for more tests
Actually, Nancy Keelan says, demand more tests. For more than three years, Keelan says, she complained to her gynecologist about irregular, heavy bleeding, and for three years he told her she was entering menopause and not to worry. Keelan says it turned out she had both advanced endometrial and ovarian cancer. "I believe he missed my diagnosis five times," says Keelan, who was 46 when she got her correct diagnosis.
Keelan, a registered nurse, now speaks to women's groups, telling them not to let more than three weeks go by if they're having new, strange symptoms. She says if the doctor tells you it's no big deal, you can frame your request this way: Tell your doctor you know it might be nothing, but would it do any harm to have a simple test? She says a simple ultrasound, would have caught her cancer much earlier.
2. Ask, "What else could my illness be?"
Let's say you've been experiencing shortness of breath when you exercise, and your doctor tells you you're just out of shape. You can ask your doctor if it could possibly be something more dangerous. Dr. Mark Graber, chief of medicine at the Veteran's Administration in Northpoint, New York, says the single most common cause of misdiagnosis is a doctor's failure to consider other possibilities after an initial diagnosis is reached. "It's called premature closing -- the minute they come up with a diagnosis, they don't think about a better solution," he says.
3. Don't assume no news is good news
Another source of misdiagnosis: Lab results get lost or forgotten. A study by Dr. Tejal Gandhi at Harvard Medical School found that up to 33 percent of physicians did not always notify patients about abnormal test results. "No news is not good news," says Dr. Saul Weingart, vice president for patient safety at Dana Farber Cancer Institute. "It might be that the report fell down behind someone's desk."
4. Assume your doctors don't talk to one another
Our experts said doctors often don't share information about test results. One piece of advice: Use that conference call function on your cell phone. Make phone appointments with your doctors at the same time, and then conference them all together.
5. Be wary when your doctors work in shifts
The title of Gandhi's 2005 study in the Annals of Internal Medicine says it all: "Fumbled Handoffs: One Dropped Ball after Another." In it, she describes how a hospital patient's tuberculosis was misdiagnosed partly because test results weren't passed on when doctors changed shifts.
By Elizabeth CohenCNN
ATLANTA, Georgia -- The celebrity was John Ritter.
The actor died in 2003 of an aortic dissection -- a tearing of the major artery that comes out of the heart. His widow later settled a wrongful death lawsuit against a California hospital, alleging his condition had been misdiagnosed "at least twice."
Experts who study malpractice cases and autopsy reports say certain diseases are misdiagnosed over and over again. It's worth knowing what they are so you won't be a victim.
1. Aortic dissection: Sometimes aortic dissections are easy to diagnose -- a patient feels a distinct tearing sensation in his or her chest. But other times they're pretty easy to miss because the symptoms could point to other diseases, says Dr. Robert Bonow, past president of the American Heart Association. "Sometimes it feels like heartburn," he says.
2. Cancer: In a Harvard study of malpractice claims in the U.S., cancer was far and away the most misdiagnosed illness, primarily breast and colorectal. Study authors attributed this to doctors failing to stick to cancer screening guidelines.
3. Clogged arteries: Sometimes doctors tell patients they're short of breath because they're out of shape, when it's actually coronary artery disease, says Bonow, who's also the chief of cardiology at Northwestern Medical School.
4. Heart attack: Sound strange? How could a doctor miss a heart attack? Bonow says the big and obvious attack -- the one where someone clutches his or her chest and falls to the floor, the one Bonow calls "the Hollywood heart attack" -- isn't always so clear. Sometimes the only signs of a heart attack are a sense of fullness in the chest, nausea and a general sense of not feeling well.
5. Infection: In the Harvard study, infection followed cancer as the most misdiagnosed condition.
So how can you keep yourself from becoming a victim of misdiagnosis?
1. Ask for more tests
Actually, Nancy Keelan says, demand more tests. For more than three years, Keelan says, she complained to her gynecologist about irregular, heavy bleeding, and for three years he told her she was entering menopause and not to worry. Keelan says it turned out she had both advanced endometrial and ovarian cancer. "I believe he missed my diagnosis five times," says Keelan, who was 46 when she got her correct diagnosis.
Keelan, a registered nurse, now speaks to women's groups, telling them not to let more than three weeks go by if they're having new, strange symptoms. She says if the doctor tells you it's no big deal, you can frame your request this way: Tell your doctor you know it might be nothing, but would it do any harm to have a simple test? She says a simple ultrasound, would have caught her cancer much earlier.
2. Ask, "What else could my illness be?"
Let's say you've been experiencing shortness of breath when you exercise, and your doctor tells you you're just out of shape. You can ask your doctor if it could possibly be something more dangerous. Dr. Mark Graber, chief of medicine at the Veteran's Administration in Northpoint, New York, says the single most common cause of misdiagnosis is a doctor's failure to consider other possibilities after an initial diagnosis is reached. "It's called premature closing -- the minute they come up with a diagnosis, they don't think about a better solution," he says.
3. Don't assume no news is good news
Another source of misdiagnosis: Lab results get lost or forgotten. A study by Dr. Tejal Gandhi at Harvard Medical School found that up to 33 percent of physicians did not always notify patients about abnormal test results. "No news is not good news," says Dr. Saul Weingart, vice president for patient safety at Dana Farber Cancer Institute. "It might be that the report fell down behind someone's desk."
4. Assume your doctors don't talk to one another
Our experts said doctors often don't share information about test results. One piece of advice: Use that conference call function on your cell phone. Make phone appointments with your doctors at the same time, and then conference them all together.
5. Be wary when your doctors work in shifts
The title of Gandhi's 2005 study in the Annals of Internal Medicine says it all: "Fumbled Handoffs: One Dropped Ball after Another." In it, she describes how a hospital patient's tuberculosis was misdiagnosed partly because test results weren't passed on when doctors changed shifts.
ECCO: Acupuncture -- Real or Fake -- Helps Relieve Nausea in Cancer Patients
BARCELONA, Spain, Sept. 27 -- Acupuncture failed to prevent nausea in cancer patients undergoing radiation any better than a sham procedure -- but the vast majority of the patients in both groups thought the needles were effective.
"Both groups of patients reported they believed the treatment has been invasive and effective and they would do it again," Ann Enblom, a physiotherapist and doctoral student at Sweden's Linkoping University, told attendees at the European CanCer Organisation meeting here.
Previous studies have shown that about 63% of patients who undergo cancer radiotherapy suffer from nausea. Compared with that figure, both real and sham acupuncture showed results.
"We found that 37% of our patients who actually had the needles placed in the acupuncture sessions experienced nausea compared with 31% of the patients who had the sham needle procedure," Enblom said, noting that there was no statistically significant difference between those figures.
Enblom and colleagues recruited 237 cancer patients who were undergoing radiation therapy, a procedure that often results in nausea and vomiting that can continue through the course of treatment and beyond. She reported on 110 patients who received acupuncture and 105 patients who received the sham procedure close to, but not at the actual acupuncture site.
The actual acupuncture needles were placed in the wrist, a few centimeters below the palm in the traditional P6 location that Chinese traditional medicine sites as the place the thin needles need to be inserted to prevent nausea.
The sham procedure used a device that causes the needle to retract into the tube once it touches the skin -- much the way trick knives push backwards into the hilt of the knife when someone is "stabbed" on stage. Enblom said almost all the patients receiving the sham procedure thought they had actually been properly needled.
The patients underwent the needling process for 30 minutes two to three times a week for the five-week course of radiotherapy.
The number of days on which patients had nausea did not differ statistically between the groups. Those getting acupuncture had 19 days of nausea during the treatment; those getting the sham treatment had 17 days of nausea.
Similarly, about 28% of the acupuncture patients experienced vomiting during the study period compared with 24% of those getting the sham treatment -- again, a non-significant difference, Enblom reported.
When patients were asked about the treatment:
93% of the actual acupuncture patients reported that they believed the procedure had "moderate" to "much" effectiveness for them.
96% of the sham acupuncture patients reported they believed the procedure had "moderate" to "much" effectiveness for them.
89% of both groups expressed "moderate" to "much" interest in using acupuncture again.
Alexander Eggermont, M.D., Ph.D., Erasmus University Medical School, Rotterdam
"There have been people -- especially in the alternative and complementary medicine field -- who have said these types of well-designed studies can't be done for treatments such as acupuncture," said Alexander Edgemont, M.D., of Erasmus University in Rotterdam, the Netherlands, who acted as moderator at the session. The Swedish study showed that such studies can be accomplished, he said.
While the study clearly shows that acupuncture is no more successful than non-acupuncture in controlling nausea, he noted that the big difference between Enblom's patients and those who have undergone radiation treatment without acupuncture indicates the potent "placebo" effect that can occur in clinical trials.
"I think this study underscores why it is necessary in clinical trials that we have control groups," he said.
"Our study may indicate that attitudes and expectations play a major role in the experience of the effect of the treatment," Enblom said.
A similar study comparing acupuncture, a sham procedure, and conventional treatment for low-back pain was reported in the Sept. 24 issue of Archives of Internal Medicine. That study, too, found sham acupuncture worked just as well as the real thing. (See: Acupuncture Tops Conventional Therapy for Low-Back Pain) Primary source: European Journal of Cancer SupplementsSource reference: S. Borjeson et al, "Invasive acupuncture for radiotherapy-induced nausea and vomiting is not more effective than placebo acupuncture, Abstract P#1103", European Journal of Cancer Supplements, Vol 5 No 4, Page 142
BARCELONA, Spain, Sept. 27 -- Acupuncture failed to prevent nausea in cancer patients undergoing radiation any better than a sham procedure -- but the vast majority of the patients in both groups thought the needles were effective.
"Both groups of patients reported they believed the treatment has been invasive and effective and they would do it again," Ann Enblom, a physiotherapist and doctoral student at Sweden's Linkoping University, told attendees at the European CanCer Organisation meeting here.
Previous studies have shown that about 63% of patients who undergo cancer radiotherapy suffer from nausea. Compared with that figure, both real and sham acupuncture showed results.
"We found that 37% of our patients who actually had the needles placed in the acupuncture sessions experienced nausea compared with 31% of the patients who had the sham needle procedure," Enblom said, noting that there was no statistically significant difference between those figures.
Enblom and colleagues recruited 237 cancer patients who were undergoing radiation therapy, a procedure that often results in nausea and vomiting that can continue through the course of treatment and beyond. She reported on 110 patients who received acupuncture and 105 patients who received the sham procedure close to, but not at the actual acupuncture site.
The actual acupuncture needles were placed in the wrist, a few centimeters below the palm in the traditional P6 location that Chinese traditional medicine sites as the place the thin needles need to be inserted to prevent nausea.
The sham procedure used a device that causes the needle to retract into the tube once it touches the skin -- much the way trick knives push backwards into the hilt of the knife when someone is "stabbed" on stage. Enblom said almost all the patients receiving the sham procedure thought they had actually been properly needled.
The patients underwent the needling process for 30 minutes two to three times a week for the five-week course of radiotherapy.
The number of days on which patients had nausea did not differ statistically between the groups. Those getting acupuncture had 19 days of nausea during the treatment; those getting the sham treatment had 17 days of nausea.
Similarly, about 28% of the acupuncture patients experienced vomiting during the study period compared with 24% of those getting the sham treatment -- again, a non-significant difference, Enblom reported.
When patients were asked about the treatment:
93% of the actual acupuncture patients reported that they believed the procedure had "moderate" to "much" effectiveness for them.
96% of the sham acupuncture patients reported they believed the procedure had "moderate" to "much" effectiveness for them.
89% of both groups expressed "moderate" to "much" interest in using acupuncture again.
Alexander Eggermont, M.D., Ph.D., Erasmus University Medical School, Rotterdam
"There have been people -- especially in the alternative and complementary medicine field -- who have said these types of well-designed studies can't be done for treatments such as acupuncture," said Alexander Edgemont, M.D., of Erasmus University in Rotterdam, the Netherlands, who acted as moderator at the session. The Swedish study showed that such studies can be accomplished, he said.
While the study clearly shows that acupuncture is no more successful than non-acupuncture in controlling nausea, he noted that the big difference between Enblom's patients and those who have undergone radiation treatment without acupuncture indicates the potent "placebo" effect that can occur in clinical trials.
"I think this study underscores why it is necessary in clinical trials that we have control groups," he said.
"Our study may indicate that attitudes and expectations play a major role in the experience of the effect of the treatment," Enblom said.
A similar study comparing acupuncture, a sham procedure, and conventional treatment for low-back pain was reported in the Sept. 24 issue of Archives of Internal Medicine. That study, too, found sham acupuncture worked just as well as the real thing. (See: Acupuncture Tops Conventional Therapy for Low-Back Pain) Primary source: European Journal of Cancer SupplementsSource reference: S. Borjeson et al, "Invasive acupuncture for radiotherapy-induced nausea and vomiting is not more effective than placebo acupuncture, Abstract P#1103", European Journal of Cancer Supplements, Vol 5 No 4, Page 142
ECCO: Breast Cancer Risk Up for Women Consuming Three Alcoholic Drinks a Day
BARCELONA, Spain, Sept. 27 -- Women who consume three of more alcoholic drinks a day have a 30% greater risk of developing breast cancer than women who averages one drink. "It doesn't seem to matter whether the alcohol comes in the form of beer, wine, or spirits," said Yan Li, M.D., Ph.D., of Kaiser Permanente Medical Care in Oakland, Calif., and colleagues, reported at the European Cancer Care Organization meeting here.
They reviewed 70,033 records of patients at Kaiser Permanent from 1978 through 1985. By 2004, breast cancer had been diagnosed in 2,829 of these women. The role of specific beverage types was studied among 37,879 women consuming one drink per month. Of that group, 1,509 subsequently were diagnosed with breast cancer.
They found that 10,570 of the women were primarily wine drinkers, 3,783 preferred spirits, and 2,702 drank beer. Another 20,824 recorded no particular preference.
Dr. Li said she tried to find a relationship between breast cancer and the type of alcohol consumed but did not identify any significant correlations. For example, she said the relative risk of developing breast cancer when comparing women who had specific drink preferences with those with no drink preference was 1.06 for wine drinkers; 1.02 for liquor drinkers, and 1.02 for beer drinkers. The confidence limits crossed unity in each case, meaning the results would not be considered significant.
"We also looked at the type of wine - whether drinking red wine or white wine made a difference - and we could not find a significant difference there either," Dr. Li said.
However, when the researchers analyzed the amount of drinking, there was a pattern, she said. When compared with women who had less than one drink a day:
The relative risk for woman consuming one to two drinks a day was 1.1 - a 10% increased risk for breast cancer, but not a significant difference.
The relative risk or women taking three or more drinks per day was 1.3 - or 30%.
Dr. Li said that when the data were analyzed for type and amount of drink a similar pattern for each type of alcohol was observed - the more drinks of any particular type of alcoholic beverage increased the risk of breast cancer.
"We believe that the culprit is alcohol itself," she said.
Why alcohol should cause breast cancer remains a mystery, said oncologist John Smyth, M.D., of the Edinburgh Cancer Research Center at the University of Edinburgh in Scotland.
"I don't think anyone has a very good idea about what the mechanism of action could be," said Dr. Smyth, president of the Federation of European Cancer Societies, which sponsors the biennial ECCO meeting.
"It appears, like many things in life, that moderation is the best approach with alcohol," he said. "We believe that alcohol has some benefits but when can have detrimental effects when taken to excess." Primary source: European Journal of Cancer Supplements, Vol 5 No 4, Page 161
Source reference: Yan Li et al, "Wine, liquor, beer, and risk of breast cancer" Abstract P#1201, European Journal of Cancer Supplements, Vol 5 No 4, Page 161
BARCELONA, Spain, Sept. 27 -- Women who consume three of more alcoholic drinks a day have a 30% greater risk of developing breast cancer than women who averages one drink. "It doesn't seem to matter whether the alcohol comes in the form of beer, wine, or spirits," said Yan Li, M.D., Ph.D., of Kaiser Permanente Medical Care in Oakland, Calif., and colleagues, reported at the European Cancer Care Organization meeting here.
They reviewed 70,033 records of patients at Kaiser Permanent from 1978 through 1985. By 2004, breast cancer had been diagnosed in 2,829 of these women. The role of specific beverage types was studied among 37,879 women consuming one drink per month. Of that group, 1,509 subsequently were diagnosed with breast cancer.
They found that 10,570 of the women were primarily wine drinkers, 3,783 preferred spirits, and 2,702 drank beer. Another 20,824 recorded no particular preference.
Dr. Li said she tried to find a relationship between breast cancer and the type of alcohol consumed but did not identify any significant correlations. For example, she said the relative risk of developing breast cancer when comparing women who had specific drink preferences with those with no drink preference was 1.06 for wine drinkers; 1.02 for liquor drinkers, and 1.02 for beer drinkers. The confidence limits crossed unity in each case, meaning the results would not be considered significant.
"We also looked at the type of wine - whether drinking red wine or white wine made a difference - and we could not find a significant difference there either," Dr. Li said.
However, when the researchers analyzed the amount of drinking, there was a pattern, she said. When compared with women who had less than one drink a day:
The relative risk for woman consuming one to two drinks a day was 1.1 - a 10% increased risk for breast cancer, but not a significant difference.
The relative risk or women taking three or more drinks per day was 1.3 - or 30%.
Dr. Li said that when the data were analyzed for type and amount of drink a similar pattern for each type of alcohol was observed - the more drinks of any particular type of alcoholic beverage increased the risk of breast cancer.
"We believe that the culprit is alcohol itself," she said.
Why alcohol should cause breast cancer remains a mystery, said oncologist John Smyth, M.D., of the Edinburgh Cancer Research Center at the University of Edinburgh in Scotland.
"I don't think anyone has a very good idea about what the mechanism of action could be," said Dr. Smyth, president of the Federation of European Cancer Societies, which sponsors the biennial ECCO meeting.
"It appears, like many things in life, that moderation is the best approach with alcohol," he said. "We believe that alcohol has some benefits but when can have detrimental effects when taken to excess." Primary source: European Journal of Cancer Supplements, Vol 5 No 4, Page 161
Source reference: Yan Li et al, "Wine, liquor, beer, and risk of breast cancer" Abstract P#1201, European Journal of Cancer Supplements, Vol 5 No 4, Page 161
Stressful Events May Increase Breast Cancer Recurrence Risk
ROCHESTER, N.Y., Sept. 27 -- Breast cancer patients with a history of traumatic or stressful life events have a two-fold increased risk of recurrence, investigators here have found.
Patients reporting one or more traumatic or stressful events had a median disease-free interval of 31 months compared with 62 months for patients with no such events, Oxana Palesh, Ph.D., of the University of Rochester, and colleagues reported in the September issue of the Journal of Psychosomatic Research.
The findings support the view that traumatic or stressful events have long-lasting effects on stress-response systems, such as the hypothalamic-pituitary-adrenal (HPA) axis.
"This body of research may lead to a new understanding of psychosocial risk factors for disease progression and may result in novel interventions designed to buffer the adverse effects of earlier stressful or traumatic life events on the hyperactivation of the HPA axis and potentially ameliorate the impact of previous trauma and subsequent development and progression of cancer," the authors concluded.
Despite a widely held belief that stress can influence the clinical course of breast cancer, research on the issue has yielded inconsistent results.
Several prior studies focused on dysregulation of the HPA response, which has an association with breast cancer progression, Dr. Palesh and colleagues noted. Prolonged exposure to stress leads to HPA-mediated endocrine activation and increased production of cortisol, which diverts biological systems from normal functions to respond to the threat posed by stress.
"Extended periods of stress and trauma and its resulting cortisol production may interfere with the body's ability to fight off cancer progression," said Dr. Palesh. "When there is consistent, long-term stress in the body, the elevated cortisol level may change the body's normal rhythms and potentially reduce resistance to tumor growth."
The current study involved 94 patients with metastatic or recurrent breast cancer. Thirty-nine reported traumatic life events, 27 reported a history of stressful events, and 28 reported no such experiences. Traumatic events included childhood sexual abuse, rape, life-threatening injury, or suicide of a family member. Stressful events included adoption, a parent's death, living with a mother-in-law, earthquake, divorce, and imprisonment of a relative.
Patients in the three groups did not differ substantially in clinical and demographic variables.
Women with a history of traumatic events had a median disease-free interval of 30 months. Those with a history of stressful life experiences had a median disease-free interval of 37 months. In contrast, women reporting no such history had a median survival exceeding five years.
Although dysregulation of the HPA axis has been postulated as an underlying mechanism of increased risk in breast cancer, cortisol levels did not differ significantly among the three groups of patients. The finding is consistent with previous research showing "flattened" or lower cortisol levels in cancer patients compared with health controls.
The absence of cortisol elevations suggests "the physiology of metastatic breast cancer might have incremented any potential variability in cortisol itself that is usually present in healthy people and even in people with less severe cancer disease," the authors said. "These findings support the disrupted feedback inhibition model of response to stress rather than the hypersensitivity as previously believed."
The authors had no disclosures. The study was supported by the National Institute on Aging and the National Cancer Institute. Primary source: Journal of Psychosomatic ResearchSource reference: Palesh O et al. "Stress history and breast cancer recurrence." J Psychsom Res 2007;63:233-239.
ROCHESTER, N.Y., Sept. 27 -- Breast cancer patients with a history of traumatic or stressful life events have a two-fold increased risk of recurrence, investigators here have found.
Patients reporting one or more traumatic or stressful events had a median disease-free interval of 31 months compared with 62 months for patients with no such events, Oxana Palesh, Ph.D., of the University of Rochester, and colleagues reported in the September issue of the Journal of Psychosomatic Research.
The findings support the view that traumatic or stressful events have long-lasting effects on stress-response systems, such as the hypothalamic-pituitary-adrenal (HPA) axis.
"This body of research may lead to a new understanding of psychosocial risk factors for disease progression and may result in novel interventions designed to buffer the adverse effects of earlier stressful or traumatic life events on the hyperactivation of the HPA axis and potentially ameliorate the impact of previous trauma and subsequent development and progression of cancer," the authors concluded.
Despite a widely held belief that stress can influence the clinical course of breast cancer, research on the issue has yielded inconsistent results.
Several prior studies focused on dysregulation of the HPA response, which has an association with breast cancer progression, Dr. Palesh and colleagues noted. Prolonged exposure to stress leads to HPA-mediated endocrine activation and increased production of cortisol, which diverts biological systems from normal functions to respond to the threat posed by stress.
"Extended periods of stress and trauma and its resulting cortisol production may interfere with the body's ability to fight off cancer progression," said Dr. Palesh. "When there is consistent, long-term stress in the body, the elevated cortisol level may change the body's normal rhythms and potentially reduce resistance to tumor growth."
The current study involved 94 patients with metastatic or recurrent breast cancer. Thirty-nine reported traumatic life events, 27 reported a history of stressful events, and 28 reported no such experiences. Traumatic events included childhood sexual abuse, rape, life-threatening injury, or suicide of a family member. Stressful events included adoption, a parent's death, living with a mother-in-law, earthquake, divorce, and imprisonment of a relative.
Patients in the three groups did not differ substantially in clinical and demographic variables.
Women with a history of traumatic events had a median disease-free interval of 30 months. Those with a history of stressful life experiences had a median disease-free interval of 37 months. In contrast, women reporting no such history had a median survival exceeding five years.
Although dysregulation of the HPA axis has been postulated as an underlying mechanism of increased risk in breast cancer, cortisol levels did not differ significantly among the three groups of patients. The finding is consistent with previous research showing "flattened" or lower cortisol levels in cancer patients compared with health controls.
The absence of cortisol elevations suggests "the physiology of metastatic breast cancer might have incremented any potential variability in cortisol itself that is usually present in healthy people and even in people with less severe cancer disease," the authors said. "These findings support the disrupted feedback inhibition model of response to stress rather than the hypersensitivity as previously believed."
The authors had no disclosures. The study was supported by the National Institute on Aging and the National Cancer Institute. Primary source: Journal of Psychosomatic ResearchSource reference: Palesh O et al. "Stress history and breast cancer recurrence." J Psychsom Res 2007;63:233-239.
Some Diabetes Treatments as Bad as the Disease
CHICAGO, Sept. 27 -- Treatment for type 2 diabetes may rival in inconvenience the complications of the disease, researchers here found. Patients rated the burden of comprehensive diabetes care -- intensive control of diabetes, blood pressure, and other risk factors -- similar to having angina, diabetic nerve damage, or diabetic kidney damage (all P>0.04), reported Elbert S. Huang, M.D., M.P.H., of the University of Chicago here, and colleagues, in the October issue of Diabetes Care.
In their medical cost-effectiveness analysis, quality of life during intensive glucose control was likewise rated similar to having diabetic neuropathy (P>0.01).
The findings may have implications for compliance as well as for efforts to improve disease management, the researchers said.
"In the near future, the results of the Action to Control Cardiovascular Risk in Diabetes trial may actually lead to even lower risk factor goals that will require even greater use of medications to achieve them," they said, but "taking multiple medications on a routine basis represents a significant burden for many patients."
The researchers interviewed 701 adults with type 2 diabetes who were attending clinics in the Chicago area. Most participants were either black (38%) or Latino (24%). The mean age was 63.
Over their average 9.9 years with a diabetes diagnosis, a substantial proportion had experienced a microvascular complication (23%) and 30% reported having cardiovascular complications. Patients typically used only oral diabetes medications (61%), but 25% also used insulin and 14% did not take any glucose control medication.
In the face-to-face interviews, patients were asked their preference on quality-of-life tradeoffs for 10 years with a particular complication or treatment and a progressively shorter period of time in perfect health.
The researchers described the daily experience of each treatment, associated laboratory testing, and likelihood of side effects. Patients were asked to focus on quality of life effects of each treatment rather than its long-term benefit against complications.
Participants generally rated intensive treatment as worse than conventional treatment.
Patients thought 10 years of life during intensive glucose control treatment was worth only 6.7 years of in perfect health whereas 10 years of conventional glucose control was worth 7.6 years of perfect health (utility score 0.67 versus 0.76, P<0.01).
They rated quality of life best for diet and exercise therapy with no significant difference between the two (utility scores 0.88 and 0.89).
Patients rated quality of life lowest with comprehensive diabetes care treatment, which was described to them as intensive glucose control plus other medications. They thought 10 years of comprehensive diabetes treatment was equivalent to 6.4 years with perfect health.
The polypill, described as the same treatment regimen with a lower pill burden, didn't appear to make comprehensive treatment much easier (utility score 0.66 versus 0.64, P=NS).
In fact, comprehensive diabetes care with or without the polypill was rated similar to having angina, diabetic neuropathy, or diabetic nephropathy (utility score 0.64 and 0.66 versus 0.64, 0.66, and 0.64, all P>0.04).
Intensive glucose control, which got the lowest utility score of all the individual treatments, was rated similar to having diabetic neuropathy (utility score 0.67 versus 0.66, P>0.01).
Thus, "this quality-of-life burden appeared to arise from the prospect of multiple daily insulin injections rather than the prospect of multiple oral agents," Dr. Huang and colleagues wrote.
Overall, 10% to 18% of patients were willing to lose eight out of 10 years of perfect health to avoid diabetes treatments altogether.
By comparison, 12% to 50% of patients would make the same trade to avoid life with complications.
The researchers acknowledged that their participants, all of whom had an established professional relationship with a physician, might have been more adherent than most patients with diabetes.
Nevertheless, the findings suggest treatment-related quality of life would likely improve if health care providers can "simplify or modify current treatments through treatment innovations," they said.
But even without this, patient concerns may still be allayed through early patient education, incorporating patient preferences into treatment decisions, and by acknowledging quality-of-life concerns in public health efforts, they concluded.
The study was supported by the National Institute of Aging Career, the National Institute of Diabetes and Digestive and Kidney Diseases, the CDC, and the Chicago Center of Excellence in Health Promotion Economics. The researchers provided no information on conflicts of interest.Primary source: Diabetes CareSource reference: Huang ES, et al "Patient Perceptions of Quality of Life With Diabetes-Related Complications and Treatments" Diabetes Care 2007; 30: DOI: 10.2337/dc07-0499.
CHICAGO, Sept. 27 -- Treatment for type 2 diabetes may rival in inconvenience the complications of the disease, researchers here found. Patients rated the burden of comprehensive diabetes care -- intensive control of diabetes, blood pressure, and other risk factors -- similar to having angina, diabetic nerve damage, or diabetic kidney damage (all P>0.04), reported Elbert S. Huang, M.D., M.P.H., of the University of Chicago here, and colleagues, in the October issue of Diabetes Care.
In their medical cost-effectiveness analysis, quality of life during intensive glucose control was likewise rated similar to having diabetic neuropathy (P>0.01).
The findings may have implications for compliance as well as for efforts to improve disease management, the researchers said.
"In the near future, the results of the Action to Control Cardiovascular Risk in Diabetes trial may actually lead to even lower risk factor goals that will require even greater use of medications to achieve them," they said, but "taking multiple medications on a routine basis represents a significant burden for many patients."
The researchers interviewed 701 adults with type 2 diabetes who were attending clinics in the Chicago area. Most participants were either black (38%) or Latino (24%). The mean age was 63.
Over their average 9.9 years with a diabetes diagnosis, a substantial proportion had experienced a microvascular complication (23%) and 30% reported having cardiovascular complications. Patients typically used only oral diabetes medications (61%), but 25% also used insulin and 14% did not take any glucose control medication.
In the face-to-face interviews, patients were asked their preference on quality-of-life tradeoffs for 10 years with a particular complication or treatment and a progressively shorter period of time in perfect health.
The researchers described the daily experience of each treatment, associated laboratory testing, and likelihood of side effects. Patients were asked to focus on quality of life effects of each treatment rather than its long-term benefit against complications.
Participants generally rated intensive treatment as worse than conventional treatment.
Patients thought 10 years of life during intensive glucose control treatment was worth only 6.7 years of in perfect health whereas 10 years of conventional glucose control was worth 7.6 years of perfect health (utility score 0.67 versus 0.76, P<0.01).
They rated quality of life best for diet and exercise therapy with no significant difference between the two (utility scores 0.88 and 0.89).
Patients rated quality of life lowest with comprehensive diabetes care treatment, which was described to them as intensive glucose control plus other medications. They thought 10 years of comprehensive diabetes treatment was equivalent to 6.4 years with perfect health.
The polypill, described as the same treatment regimen with a lower pill burden, didn't appear to make comprehensive treatment much easier (utility score 0.66 versus 0.64, P=NS).
In fact, comprehensive diabetes care with or without the polypill was rated similar to having angina, diabetic neuropathy, or diabetic nephropathy (utility score 0.64 and 0.66 versus 0.64, 0.66, and 0.64, all P>0.04).
Intensive glucose control, which got the lowest utility score of all the individual treatments, was rated similar to having diabetic neuropathy (utility score 0.67 versus 0.66, P>0.01).
Thus, "this quality-of-life burden appeared to arise from the prospect of multiple daily insulin injections rather than the prospect of multiple oral agents," Dr. Huang and colleagues wrote.
Overall, 10% to 18% of patients were willing to lose eight out of 10 years of perfect health to avoid diabetes treatments altogether.
By comparison, 12% to 50% of patients would make the same trade to avoid life with complications.
The researchers acknowledged that their participants, all of whom had an established professional relationship with a physician, might have been more adherent than most patients with diabetes.
Nevertheless, the findings suggest treatment-related quality of life would likely improve if health care providers can "simplify or modify current treatments through treatment innovations," they said.
But even without this, patient concerns may still be allayed through early patient education, incorporating patient preferences into treatment decisions, and by acknowledging quality-of-life concerns in public health efforts, they concluded.
The study was supported by the National Institute of Aging Career, the National Institute of Diabetes and Digestive and Kidney Diseases, the CDC, and the Chicago Center of Excellence in Health Promotion Economics. The researchers provided no information on conflicts of interest.Primary source: Diabetes CareSource reference: Huang ES, et al "Patient Perceptions of Quality of Life With Diabetes-Related Complications and Treatments" Diabetes Care 2007; 30: DOI: 10.2337/dc07-0499.
Halting Heavy Drinking Cuts Esophageal and Head-and-Neck Cancer Risks
TORONTO, Sept. 27 -- Stopping heavy drinking can significantly reduce the risk of esophageal and head-and-neck cancers, primarily squamous-cell carcinomas, researchers here said.
In a pooled analysis of 13 studies, those who quit heavy drinking saw their risk of esophageal cancer and head and neck cancer return to normal after 20 years, according to Jürgen Rehm, Ph.D., of the Centre for Addiction and Mental Health and colleagues.
But the first few years after stopping saw a significant rise in development of both types of cancer, he and colleagues reported in the September issue of the International Journal of Cancer.
The researchers postulated that the increase immediately after quitting was the result of what they called the "sick quitter" effect, in which patients stop drinking because they are already suffering symptoms of cancer, although it had not yet been diagnosed.
But after five years in the case of esophageal cancer and 10 years for head and neck cancers, the risk begins to drop, Dr. Rehm and colleagues said.
"Alcohol cessation has very similar effects on risk for head and neck cancers as smoking cessation has on lung cancer. Dr. Rehm said. "It takes about two decades before the risk is back to the risk of those who were never drinkers or never smokers."
The finding comes from 13 case-control studies - five in esophageal cancer and eight in head and neck cancer - that included more than 5,000 cases, the researchers said. Most of the studies involved squamous-cell carcinoma.
Compared with current drinkers, people who have never used alcohol had a risk ratio for esophageal cancer of 0.37 and for head and neck cancers of0.46. Both risk reductions were significant at P<0.001.
For former drinkers (compared with current drinkers) the risk first rose and then fell:
The risk ratio for esophageal cancer in the first two years after stopping was 2.5, with a 95% confidence interval from 2.23 to 2.80, which was significant at P<0.001.
Between five and 10 years after stopping, the risk of esophageal cancer was significantly reduced (at P<0.001) with a risk ratio of 0.85 and a 95% confidence interval from 0.78 to 0.92.
By 15 years, the risk ratio for esophageal cancer was the same as that for a person who had never used alcohol - 0.37.
The risk for head and neck cancers remained high for the first 10 years after going on the wagon. The risk ratio for people between five and 10 years after they quit was 1.26, with a 95% confidence interval from 1.18 to 1.35, which was significant at P<0.001.
But between 10 and 15 years later, the risk ratio was 0.67, with a 95% confidence interval from 0.63 to 0.73, which was significant at P<0.001.
The risks did not change substantially when the researchers adjusted for smoking.
Dr. Rehm and colleagues noted that the study is limited because they treated drinking as an all-or-nothing issue, and were unable to estimate dose-response effects.
They also noted the analysis is entirely based on retrospective studies, which opens the door to various errors, including recall bias.
Nonetheless, they said, the study is comprehensive and provides the most accurate available odds ratios for alcohol cessation. "The risk reductions are quite large, especially for esophageal cancer," they said.
The study was supported by Public Works and Government Services Canada. The authors made no statement regarding potential conflicts. Primary source: International Journal of CancerSource reference: Rehm J et al. "Alcohol drinking cessation and its effect on esophageal and head and neck cancers: A pooled analysis." Int. J. Cancer2007;121:1132-37.
TORONTO, Sept. 27 -- Stopping heavy drinking can significantly reduce the risk of esophageal and head-and-neck cancers, primarily squamous-cell carcinomas, researchers here said.
In a pooled analysis of 13 studies, those who quit heavy drinking saw their risk of esophageal cancer and head and neck cancer return to normal after 20 years, according to Jürgen Rehm, Ph.D., of the Centre for Addiction and Mental Health and colleagues.
But the first few years after stopping saw a significant rise in development of both types of cancer, he and colleagues reported in the September issue of the International Journal of Cancer.
The researchers postulated that the increase immediately after quitting was the result of what they called the "sick quitter" effect, in which patients stop drinking because they are already suffering symptoms of cancer, although it had not yet been diagnosed.
But after five years in the case of esophageal cancer and 10 years for head and neck cancers, the risk begins to drop, Dr. Rehm and colleagues said.
"Alcohol cessation has very similar effects on risk for head and neck cancers as smoking cessation has on lung cancer. Dr. Rehm said. "It takes about two decades before the risk is back to the risk of those who were never drinkers or never smokers."
The finding comes from 13 case-control studies - five in esophageal cancer and eight in head and neck cancer - that included more than 5,000 cases, the researchers said. Most of the studies involved squamous-cell carcinoma.
Compared with current drinkers, people who have never used alcohol had a risk ratio for esophageal cancer of 0.37 and for head and neck cancers of0.46. Both risk reductions were significant at P<0.001.
For former drinkers (compared with current drinkers) the risk first rose and then fell:
The risk ratio for esophageal cancer in the first two years after stopping was 2.5, with a 95% confidence interval from 2.23 to 2.80, which was significant at P<0.001.
Between five and 10 years after stopping, the risk of esophageal cancer was significantly reduced (at P<0.001) with a risk ratio of 0.85 and a 95% confidence interval from 0.78 to 0.92.
By 15 years, the risk ratio for esophageal cancer was the same as that for a person who had never used alcohol - 0.37.
The risk for head and neck cancers remained high for the first 10 years after going on the wagon. The risk ratio for people between five and 10 years after they quit was 1.26, with a 95% confidence interval from 1.18 to 1.35, which was significant at P<0.001.
But between 10 and 15 years later, the risk ratio was 0.67, with a 95% confidence interval from 0.63 to 0.73, which was significant at P<0.001.
The risks did not change substantially when the researchers adjusted for smoking.
Dr. Rehm and colleagues noted that the study is limited because they treated drinking as an all-or-nothing issue, and were unable to estimate dose-response effects.
They also noted the analysis is entirely based on retrospective studies, which opens the door to various errors, including recall bias.
Nonetheless, they said, the study is comprehensive and provides the most accurate available odds ratios for alcohol cessation. "The risk reductions are quite large, especially for esophageal cancer," they said.
The study was supported by Public Works and Government Services Canada. The authors made no statement regarding potential conflicts. Primary source: International Journal of CancerSource reference: Rehm J et al. "Alcohol drinking cessation and its effect on esophageal and head and neck cancers: A pooled analysis." Int. J. Cancer2007;121:1132-37.
Opioid Resistance in Fibromyalgia Explained by Receptor Function
ANN ARBOR, Mich., Sept. 27 -- The reason that opioids seem to fizzle for fibromyalgia may be because of reduced receptor activity in regions of the brain that process and dampen pain signals, researchers here found.
Reduced µ-opioid receptor-binding potential in fibromyalgia patients was also significantly correlated with depression and emotional components of pain, reported Richard E. Harris, Ph.D., of the University of Michigan, and colleagues, in the Sept. 12 issue of the Journal of Neuroscience.
"Because these receptors are the target of opiate drugs," they wrote, "a profound reduction in the concentration or function of these receptors is consistent with a poor response of fibromyalgia patients to this class of analgesics, observed anecdotally in clinical settings."
The researchers used PET with a selective µ-opioid receptor radiotracer to assess receptor availability differences between fibromyalgia patients and healthy pain-free individuals.
Their study included 17 right-handed women with fibromyalgia (mean age 44.8, mean diagnosis duration 8.4 years) and 17 age- and sex-matched healthy controls who were part of an ongoing study of acupuncture treatment. The analysis was done on PET scans and other data collected at baseline.
No participants were taking opioids or had a history of their use. Of the 17 fibromyalgia patients, 10 were taking antidepressant medication, either serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors.
The women reported "sensory" and "affective" characteristics of their pain on the Short Form of the McGill Pain Questionnaire immediately prior to undergoing the PET scan.
Depressive symptoms were self-reported on the Center for Epidemiological Studies-Depression Scale, which is used to detect major or clinical depression.
The PET scans showed significantly less opioid receptor-binding potential overall in fibromyalgia patients than in controls (P<0.01).
Fibromyalgia patients also had significantly less opioid receptor availability in four specific regions of the brain, the left and right nucleus accumbens, the left amygdala, and the right dorsal anterior cingulate (all P<0.05).
After controlling for global opioid receptor binding potential, the difference was still significant for the left (P<0.001) and right (P<0.05) nucleus accumbens and the amygdala (P<0.005). Activity in the dorsal anterior cingulate showed a similar trend (P<0.07).
"All of these regions have previously been noted to play some role in nociception and pain," Dr. Harris and colleagues said.
But, antidepressant use in the fibromyalgia group did not explain the opioid receptor abnormalities, the researchers said.
Binding potential in these four brain regions was not significantly different in fibromyalgia patients taking serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors than among those not taking drugs in this class (all P>0.35).
Fibromyalgia patients also showed more depressive symptoms (P<0.05) with reduced opioid receptor binding within the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.
Among fibromyalgia patients, reductions in opioid receptor-binding in the left nucleus accumbens was correlated with significant increases in the emotional component of clinical pain (P<0.05)>0.50). Controlling for antidepressant medication use did not change the association.
The relative amount of emotional versus sensory pain varied between patients in correlation with differences in opioid receptor binding in the dorsal anterior cingulate (P<0.05), posterior cingulate (P<0.001), and right ventral putamen (P<0.05) with a trend for the anterior cingulate (P=0.09).
"These results suggest that in fibromyalgia patients the affective quality of pain is associated with reduced µ-opioid receptor availability throughout the cingulate and other brain regions commonly associated with pain modulation," the researchers wrote.
Alterations in central opioid neurotransmission in specific brain regions "suggest that these mechanisms, possibly as a consequence of persistent pain, are involved in the clinical presentation and even the perpetuation of symptoms in this illness," they added.
Regardless of whether the mechanism is high endogenous opioids or downregulation of opioid receptors, the findings predict a poorer response to opioid painkillers for fibromyalgia patients, they concluded.
The study was supported by grants from the Department of Army, the National Institutes of Health. Dr. Harris was supported by a National Center for Complementary and Alternative Medicine grant and another researcher was likewise supported by a National Institutes of Health grant. None of the researchers reported conflicts of interest. Primary source: The Journal of NeuroscienceSource reference: Harris RE, et al "Decreased Central µ-Opioid Receptor Availability in Fibromyalgia" J Neurosci 2007;27:10000-10006.
ANN ARBOR, Mich., Sept. 27 -- The reason that opioids seem to fizzle for fibromyalgia may be because of reduced receptor activity in regions of the brain that process and dampen pain signals, researchers here found.
Reduced µ-opioid receptor-binding potential in fibromyalgia patients was also significantly correlated with depression and emotional components of pain, reported Richard E. Harris, Ph.D., of the University of Michigan, and colleagues, in the Sept. 12 issue of the Journal of Neuroscience.
"Because these receptors are the target of opiate drugs," they wrote, "a profound reduction in the concentration or function of these receptors is consistent with a poor response of fibromyalgia patients to this class of analgesics, observed anecdotally in clinical settings."
The researchers used PET with a selective µ-opioid receptor radiotracer to assess receptor availability differences between fibromyalgia patients and healthy pain-free individuals.
Their study included 17 right-handed women with fibromyalgia (mean age 44.8, mean diagnosis duration 8.4 years) and 17 age- and sex-matched healthy controls who were part of an ongoing study of acupuncture treatment. The analysis was done on PET scans and other data collected at baseline.
No participants were taking opioids or had a history of their use. Of the 17 fibromyalgia patients, 10 were taking antidepressant medication, either serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors.
The women reported "sensory" and "affective" characteristics of their pain on the Short Form of the McGill Pain Questionnaire immediately prior to undergoing the PET scan.
Depressive symptoms were self-reported on the Center for Epidemiological Studies-Depression Scale, which is used to detect major or clinical depression.
The PET scans showed significantly less opioid receptor-binding potential overall in fibromyalgia patients than in controls (P<0.01).
Fibromyalgia patients also had significantly less opioid receptor availability in four specific regions of the brain, the left and right nucleus accumbens, the left amygdala, and the right dorsal anterior cingulate (all P<0.05).
After controlling for global opioid receptor binding potential, the difference was still significant for the left (P<0.001) and right (P<0.05) nucleus accumbens and the amygdala (P<0.005). Activity in the dorsal anterior cingulate showed a similar trend (P<0.07).
"All of these regions have previously been noted to play some role in nociception and pain," Dr. Harris and colleagues said.
But, antidepressant use in the fibromyalgia group did not explain the opioid receptor abnormalities, the researchers said.
Binding potential in these four brain regions was not significantly different in fibromyalgia patients taking serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors than among those not taking drugs in this class (all P>0.35).
Fibromyalgia patients also showed more depressive symptoms (P<0.05) with reduced opioid receptor binding within the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.
Among fibromyalgia patients, reductions in opioid receptor-binding in the left nucleus accumbens was correlated with significant increases in the emotional component of clinical pain (P<0.05)>0.50). Controlling for antidepressant medication use did not change the association.
The relative amount of emotional versus sensory pain varied between patients in correlation with differences in opioid receptor binding in the dorsal anterior cingulate (P<0.05), posterior cingulate (P<0.001), and right ventral putamen (P<0.05) with a trend for the anterior cingulate (P=0.09).
"These results suggest that in fibromyalgia patients the affective quality of pain is associated with reduced µ-opioid receptor availability throughout the cingulate and other brain regions commonly associated with pain modulation," the researchers wrote.
Alterations in central opioid neurotransmission in specific brain regions "suggest that these mechanisms, possibly as a consequence of persistent pain, are involved in the clinical presentation and even the perpetuation of symptoms in this illness," they added.
Regardless of whether the mechanism is high endogenous opioids or downregulation of opioid receptors, the findings predict a poorer response to opioid painkillers for fibromyalgia patients, they concluded.
The study was supported by grants from the Department of Army, the National Institutes of Health. Dr. Harris was supported by a National Center for Complementary and Alternative Medicine grant and another researcher was likewise supported by a National Institutes of Health grant. None of the researchers reported conflicts of interest. Primary source: The Journal of NeuroscienceSource reference: Harris RE, et al "Decreased Central µ-Opioid Receptor Availability in Fibromyalgia" J Neurosci 2007;27:10000-10006.
Genes Tied to Bad Reactions to Antidepressant Drug
By BENEDICT CAREY
Variations in two genes may increase the likelihood that a person will report suicidal thoughts after taking an antidepressant, researchers reported yesterday. The finding could help doctors develop tests to predict which patients will do well on such medications and which will react badly.
The authors of the study, which was released to reporters yesterday and will appear in The American Journal of Psychiatry on Monday, said that the findings were preliminary and would need to be verified by further testing.
The study focused on reactions to only one drug, Celexa from Forest Laboratories, and found no link between the gene variations and dangerous behavior like suicide attempts.
This distinction is critical, because doctors do not know whether people who report thoughts of ending their lives are at increased risk to act on them. The one patient in the study who attempted suicide consistently denied having any suicidal thoughts.
The findings come at a time when psychiatrists, regulators and some former patients are locked in a furious debate about the risks of antidepressant drugs, which include products like Prozac from Eli Lilly and Zoloft from Pfizer. In recent years, health regulators have required that drug makers post strong warnings on antidepressant labels, saying that some young patients may be at increased risk of suicidal thoughts and behavior.
Some psychiatrists say the warnings have scared off patients who would benefit from the drugs — based largely on reports of suicidal thinking, which may not increase the risk of suicide itself.
“What I would say is that this study is a wake-up call, that we may have the opportunity to use genomic tests to guide personalized care for depression,” said Dr. Thomas Insel, director of the National Institute of Mental Health, which helped finance the study.
But Dr. Insel added that the genetic test “is not yet ready for prime time.”
The researchers used data from a large government-financed depression study that included more than 4,000 adult patients. They found that about 6 percent of these patients reported having thoughts of suicide after taking the drug, usually within the first few weeks of starting treatment.
They then analyzed blood samples from 120 of those who reported the suicidal thoughts, looking to see whether variations in certain genes were especially common in them.
The scientists found that 36 percent of the patients who had markers for two gene variations reported suicidal thoughts — a more than 10-fold risk compared with those with neither of the gene markers.
These patients were also far less likely to recover taking the drug. Both markers were in genes that affect how the brain processes a chemical messenger called glutamate, which works to activate neurons.
If genetic tests are developed, “they could add to the whole clinical picture,” said Dr. Francis McMahon, chief of the genetics and mood disorders unit of the National Institute of Mental Health and the senior author of the study.
“If a patient tells me he thinks his life is not worth living, or I know he’s at risk of having that reaction, I’m going to monitor him more closely or treat him differently,” Dr. McMahon said.
The researchers searched for links to 68 genes in the patients’ blood samples that might influence mood states, but these are clearly not the only genes that could be involved in the emergence of suicidal thoughts.
Many of the patients who reported a sudden urge to end their lives did not have either of the gene variations found to put people at high risk.
By BENEDICT CAREY
Variations in two genes may increase the likelihood that a person will report suicidal thoughts after taking an antidepressant, researchers reported yesterday. The finding could help doctors develop tests to predict which patients will do well on such medications and which will react badly.
The authors of the study, which was released to reporters yesterday and will appear in The American Journal of Psychiatry on Monday, said that the findings were preliminary and would need to be verified by further testing.
The study focused on reactions to only one drug, Celexa from Forest Laboratories, and found no link between the gene variations and dangerous behavior like suicide attempts.
This distinction is critical, because doctors do not know whether people who report thoughts of ending their lives are at increased risk to act on them. The one patient in the study who attempted suicide consistently denied having any suicidal thoughts.
The findings come at a time when psychiatrists, regulators and some former patients are locked in a furious debate about the risks of antidepressant drugs, which include products like Prozac from Eli Lilly and Zoloft from Pfizer. In recent years, health regulators have required that drug makers post strong warnings on antidepressant labels, saying that some young patients may be at increased risk of suicidal thoughts and behavior.
Some psychiatrists say the warnings have scared off patients who would benefit from the drugs — based largely on reports of suicidal thinking, which may not increase the risk of suicide itself.
“What I would say is that this study is a wake-up call, that we may have the opportunity to use genomic tests to guide personalized care for depression,” said Dr. Thomas Insel, director of the National Institute of Mental Health, which helped finance the study.
But Dr. Insel added that the genetic test “is not yet ready for prime time.”
The researchers used data from a large government-financed depression study that included more than 4,000 adult patients. They found that about 6 percent of these patients reported having thoughts of suicide after taking the drug, usually within the first few weeks of starting treatment.
They then analyzed blood samples from 120 of those who reported the suicidal thoughts, looking to see whether variations in certain genes were especially common in them.
The scientists found that 36 percent of the patients who had markers for two gene variations reported suicidal thoughts — a more than 10-fold risk compared with those with neither of the gene markers.
These patients were also far less likely to recover taking the drug. Both markers were in genes that affect how the brain processes a chemical messenger called glutamate, which works to activate neurons.
If genetic tests are developed, “they could add to the whole clinical picture,” said Dr. Francis McMahon, chief of the genetics and mood disorders unit of the National Institute of Mental Health and the senior author of the study.
“If a patient tells me he thinks his life is not worth living, or I know he’s at risk of having that reaction, I’m going to monitor him more closely or treat him differently,” Dr. McMahon said.
The researchers searched for links to 68 genes in the patients’ blood samples that might influence mood states, but these are clearly not the only genes that could be involved in the emergence of suicidal thoughts.
Many of the patients who reported a sudden urge to end their lives did not have either of the gene variations found to put people at high risk.
Heart Patients’ Guidelines for Having Other Surgery
By LAWRENCE K. ALTMAN
The nation’s two leading heart groups issued new guidelines yesterday about what should be done for patients with heart disease before they undergo surgery on other parts of the body.
The aim is to reduce a heart patient’s risk of complications during and after an operation. The recommendations were based on a critical review of studies, particularly those published since the two groups’ last guidelines, in 2002.
A panel of experts from the American College of Cardiology and the American Heart Association wrote the guidelines, which affect the quality and cost of care.
The guidelines, 82 pages long, cover a number of wide-ranging medical issues. One is whether to stop taking certain prescribed drugs before an operation. Another is whether to implant stents or perform coronary bypass surgery before conducting other types of elective surgery.
The decisions depend on the urgency of the operation, its type and risk, a patient’s general ability to function, and the hospital where the surgery is performed, the panel said.
Although the safety of surgery for heart patients has improved in recent years, problems affecting the heart and blood vessels are the most common and treatable complications of nonheart operations. For example, patients have a 40 percent to 70 percent increased risk of dying if they have a painful heart attack after surgery, the panelists wrote.
If heart patients need emergency nonheart surgery, doctors should forgo heart testing and send a patient straight to an operating room, said the panel’s chairman, Dr. Lee A. Fleisher, chairman of anesthesiology and critical care at the University of Pennsylvania School of Medicine.
But many people with heart disease can safely undergo non-emergency operations without first undergoing the extensive testing that is common practice.
Doctors often do many screening tests and then repair the heart problem to prepare the patient for noncardiac surgery. For example, doctors often perform an artery-opening procedure and implant a stent or do a coronary bypass operation.
The panel said that such interventions are rarely necessary to lower the risk of nonheart surgery unless a patient needed the intervention in any case.
The guidelines recommend that patients undergo evaluation and treatment before noncardiac surgery only for active heart problems like severe angina, late-stage heart failure, serious heart rhythm abnormalities (arrhythmias) and severe heart valve disease.
The guidelines also say new studies show that patients should not stop taking the cholesterol-lowering drugs called statins before surgery, an issue not addressed in earlier versions.
Another recommendation concerns the use of anticlotting drugs that patients take after they have received a stent. In the past, such patients were advised to stop taking such drugs before surgery because of the risk of bleeding.
Newer information shows that anticlotting drug treatment is important after stent placement, and the guidelines urge patients to stop taking such drugs for as short a time as possible.
The panel said that for many people the need for nonheart surgery is their first chance to receive evaluation for the risk for heart disease.
In analyzing the published studies, the panel found that most were too small to provide meaningful statistical results, increasing the difficulty of making recommendations. “A lot of the studies should never have been started or published,” Dr. Fleisher said in an interview.
The panel also urged researchers to conduct sufficiently large clinical trials to clarify areas where data is lacking. Among them are the safety and effectiveness of starting and stopping drugs like aspirin, statins and beta blockers before surgery.
The guidelines will be published in the Oct. 23 issue of the heart association’s journal, Circulation.
By LAWRENCE K. ALTMAN
The nation’s two leading heart groups issued new guidelines yesterday about what should be done for patients with heart disease before they undergo surgery on other parts of the body.
The aim is to reduce a heart patient’s risk of complications during and after an operation. The recommendations were based on a critical review of studies, particularly those published since the two groups’ last guidelines, in 2002.
A panel of experts from the American College of Cardiology and the American Heart Association wrote the guidelines, which affect the quality and cost of care.
The guidelines, 82 pages long, cover a number of wide-ranging medical issues. One is whether to stop taking certain prescribed drugs before an operation. Another is whether to implant stents or perform coronary bypass surgery before conducting other types of elective surgery.
The decisions depend on the urgency of the operation, its type and risk, a patient’s general ability to function, and the hospital where the surgery is performed, the panel said.
Although the safety of surgery for heart patients has improved in recent years, problems affecting the heart and blood vessels are the most common and treatable complications of nonheart operations. For example, patients have a 40 percent to 70 percent increased risk of dying if they have a painful heart attack after surgery, the panelists wrote.
If heart patients need emergency nonheart surgery, doctors should forgo heart testing and send a patient straight to an operating room, said the panel’s chairman, Dr. Lee A. Fleisher, chairman of anesthesiology and critical care at the University of Pennsylvania School of Medicine.
But many people with heart disease can safely undergo non-emergency operations without first undergoing the extensive testing that is common practice.
Doctors often do many screening tests and then repair the heart problem to prepare the patient for noncardiac surgery. For example, doctors often perform an artery-opening procedure and implant a stent or do a coronary bypass operation.
The panel said that such interventions are rarely necessary to lower the risk of nonheart surgery unless a patient needed the intervention in any case.
The guidelines recommend that patients undergo evaluation and treatment before noncardiac surgery only for active heart problems like severe angina, late-stage heart failure, serious heart rhythm abnormalities (arrhythmias) and severe heart valve disease.
The guidelines also say new studies show that patients should not stop taking the cholesterol-lowering drugs called statins before surgery, an issue not addressed in earlier versions.
Another recommendation concerns the use of anticlotting drugs that patients take after they have received a stent. In the past, such patients were advised to stop taking such drugs before surgery because of the risk of bleeding.
Newer information shows that anticlotting drug treatment is important after stent placement, and the guidelines urge patients to stop taking such drugs for as short a time as possible.
The panel said that for many people the need for nonheart surgery is their first chance to receive evaluation for the risk for heart disease.
In analyzing the published studies, the panel found that most were too small to provide meaningful statistical results, increasing the difficulty of making recommendations. “A lot of the studies should never have been started or published,” Dr. Fleisher said in an interview.
The panel also urged researchers to conduct sufficiently large clinical trials to clarify areas where data is lacking. Among them are the safety and effectiveness of starting and stopping drugs like aspirin, statins and beta blockers before surgery.
The guidelines will be published in the Oct. 23 issue of the heart association’s journal, Circulation.
Thursday, September 27, 2007
New drug makes weight loss safer
Dr. Nir Barak of TAU University has created a new diet drug with fewer side effects
TEL AVIV – More than 60 percent of American women are overweight, with nearly a third falling into the category of obese and at greater risk of cancer, heart disease and diabetes. Until now, there has been no safe, long-term medical remedy that tackles unwanted weight gain.
Dr. Nir Barak of Tel Aviv University’s Sackler School of Medicine has developed what could be a new weight-loss wonder drug. In conjunction with the drug company Obecure, Dr. Barak developed a new formulation called HistaleanTM, based on betahistine, an approved drug marketed worldwide for the treatment of vertigo. Betahistine has been available to health authorities for over 30 years.
Betahistine is believed to block receptors in the brain – the H1 and H3 receptors – which are connected to one’s sense of fullness and desire to eat fatty foods. It has an excellent safety profile and has been used for treatment by more than 100 million patients suffering from vertigo and dizziness in Canada and Europe.
The repurposed pill, Histalean, has been found to quell the desire to consume fatty foods, and the effects have been most pronounced in women.
According to the U.S. Center for Disease Control, about 32% of adult American women under 54 (about 25 million women) suffer from obesity. “Our new results suggest a strong gender-and-age-effect and support the potential of the drug as a breakthrough anti-obesity agent in women 50 years old or less,” confirmed Dr. Yaffa Beck, Obecure’s CEO.
According to some estimates, obesity results in thousands of deaths a year and accounts for $117 billion in U.S. health care expenses annually. Clearly, a breakthrough in this area will not only make women look and feel better, but it could save their lives as well.
A recent Phase II clinical trial of the new drug in the U.S. suggests that women under the age of 50 who took Histalean for 12 weeks lost 7 times the weight of those taking a placebo. What’s most important to the researchers involved is that none of the 281 patients, males and females aged 18-65, complained of any serious side effects.
The trial, completed this August, was supervised by U.S. weight-loss guru Dr. Robert Kushner. The women who took the pill reported, “It wasn't hard.” “I wasn't thinking about food.” “I was content.”
Dr. Barak explains why this is good news, “All the drugs in the diet pill market today have serious side effects. They may help a woman lose weight, but with that weight loss comes all sorts of bad things like depression and even suicide. Safety issues are a real concern for the FDA. But because this new drug has already been proven safe for other indications, we think Histalean has real blockbuster potential.”
The recent results were based on a double-blind, placebo-controlled study on people with a Body Mass Index ranging from 30 to 40. (A BMI of 30 and above indicate obesity.) The study was conducted at 19 investigation sites across the U.S. over a 12 week treatment period. The subgroup of high-dose Histalean-treated women lost an average of 2.91% of their weight versus placebo group which lost only 0.4 %.
Dr. Barak’s drug is also expected to compete for the $28 billion market of cholesterol-reducing drugs such as Lipitor. It could also be used in parallel with anti-psychotic drugs, which have unwanted side effects of extreme weight gain among mental health patients.
Dr. Nir Barak of TAU University has created a new diet drug with fewer side effects
TEL AVIV – More than 60 percent of American women are overweight, with nearly a third falling into the category of obese and at greater risk of cancer, heart disease and diabetes. Until now, there has been no safe, long-term medical remedy that tackles unwanted weight gain.
Dr. Nir Barak of Tel Aviv University’s Sackler School of Medicine has developed what could be a new weight-loss wonder drug. In conjunction with the drug company Obecure, Dr. Barak developed a new formulation called HistaleanTM, based on betahistine, an approved drug marketed worldwide for the treatment of vertigo. Betahistine has been available to health authorities for over 30 years.
Betahistine is believed to block receptors in the brain – the H1 and H3 receptors – which are connected to one’s sense of fullness and desire to eat fatty foods. It has an excellent safety profile and has been used for treatment by more than 100 million patients suffering from vertigo and dizziness in Canada and Europe.
The repurposed pill, Histalean, has been found to quell the desire to consume fatty foods, and the effects have been most pronounced in women.
According to the U.S. Center for Disease Control, about 32% of adult American women under 54 (about 25 million women) suffer from obesity. “Our new results suggest a strong gender-and-age-effect and support the potential of the drug as a breakthrough anti-obesity agent in women 50 years old or less,” confirmed Dr. Yaffa Beck, Obecure’s CEO.
According to some estimates, obesity results in thousands of deaths a year and accounts for $117 billion in U.S. health care expenses annually. Clearly, a breakthrough in this area will not only make women look and feel better, but it could save their lives as well.
A recent Phase II clinical trial of the new drug in the U.S. suggests that women under the age of 50 who took Histalean for 12 weeks lost 7 times the weight of those taking a placebo. What’s most important to the researchers involved is that none of the 281 patients, males and females aged 18-65, complained of any serious side effects.
The trial, completed this August, was supervised by U.S. weight-loss guru Dr. Robert Kushner. The women who took the pill reported, “It wasn't hard.” “I wasn't thinking about food.” “I was content.”
Dr. Barak explains why this is good news, “All the drugs in the diet pill market today have serious side effects. They may help a woman lose weight, but with that weight loss comes all sorts of bad things like depression and even suicide. Safety issues are a real concern for the FDA. But because this new drug has already been proven safe for other indications, we think Histalean has real blockbuster potential.”
The recent results were based on a double-blind, placebo-controlled study on people with a Body Mass Index ranging from 30 to 40. (A BMI of 30 and above indicate obesity.) The study was conducted at 19 investigation sites across the U.S. over a 12 week treatment period. The subgroup of high-dose Histalean-treated women lost an average of 2.91% of their weight versus placebo group which lost only 0.4 %.
Dr. Barak’s drug is also expected to compete for the $28 billion market of cholesterol-reducing drugs such as Lipitor. It could also be used in parallel with anti-psychotic drugs, which have unwanted side effects of extreme weight gain among mental health patients.
Discovery supports theory of Alzheimer's disease as form of diabetes
EVANSTON, Ill. --- Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.
Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)
With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.
The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer’s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)
In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer’s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.
“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”
ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.
In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.
“We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer’s brains,” said Klein, a member of Northwestern’s Cognitive Neurology and Alzheimer's Disease Center. “We’re dealing with a fundamental new connection between two fields, diabetes and Alzheimer’s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.”
Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.
They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.
“In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,” said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein’s lab. “These factors suggest that insulin resistance in the brains of those with Alzheimer’s is a response to ADDLs.”
“With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer’s treatment,” said Klein. “I think such drugs could supercede currently available Alzheimer’s drugs.”
EVANSTON, Ill. --- Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.
Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)
With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.
The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer’s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)
In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer’s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.
“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”
ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.
In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.
“We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer’s brains,” said Klein, a member of Northwestern’s Cognitive Neurology and Alzheimer's Disease Center. “We’re dealing with a fundamental new connection between two fields, diabetes and Alzheimer’s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.”
Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.
They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.
“In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,” said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein’s lab. “These factors suggest that insulin resistance in the brains of those with Alzheimer’s is a response to ADDLs.”
“With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer’s treatment,” said Klein. “I think such drugs could supercede currently available Alzheimer’s drugs.”
A Low LDL Does Not Eliminate the Risk of a Low HDL
SYDNEY, Sept. 26 -- For patients with coronary artery disease, a maximum risk reduction required not only the lowest level of LDLs, but also the highest level of HDLs, found investigators here.
That assessment emerged from a post hoc analysis of the 9,770-patient TNT (Treating to New Targets) trial which found that at five years there were fewer deaths and non-fatal events among patients who achieved an LDL of less than 70 mg/dL and a mean HDL of 61.5 mg/dL (±10.1) after three months of statin therapy (P=0.03).
"In the univariate model, the event rate was reduced by 40% in the highest [HDL] quintile relative to the lowest," Philip Barter, M.D., of the Heart Research Institute in Sydney, and colleagues, reported the finding in the Sept. 27 issue of the New England Journal of Medicine. When the data were adjusted for covariates, in the entire TNT population there was a 25% reduction in risk (HR 0.75, 95% CI 0.60-0.95) for the highest HDL quintile versus the lowest (P=0.04).
Low HDL level was known to be a "powerful predictor of increased cardiovascular risk," but it had been argued that "if the LDL cholesterol level were reduced sufficiently, the level of HDL cholesterol might become irrelevant," they wrote.
"But we knew that even when LDL was aggressively treated, there was still a risk of events," Dr. Barter said in an interview. "This analysis confirms that clearly HDL remains important. If anything I am surprised by the magnitude of its importance. So the real message is that lower [LDL] is better, yes. But that is not enough to get rid of risk associated with low HDL."
The TNT randomized coronary disease patients who had a baseline LDL of 130 mg/dL or lower to 80 mg or 10 mg of atorvastatin (Lipitor). The target LDL was less than 70 mg/dL and patients were followed for five years. Patients in the high dose arm achieved a mean LDL of 77 mg/dL and reduced cardiovascular events by 22%. (See: ACC: LDL Cholesterol of Less than 80 mg/dL Reduces Risk of Heart Attack and Stroke)
In the current study, the investigators analyzed the relationship between HDL at the end of three months of statin therapy and time to first-event risk. The data were also stratified by LDL cholesterol level.
In an interview, Christopher Cannon, M.D., of Brigham and Women's Hospital and Harvard Medical School, agreed that the finding was "important," although he pointed out that it emerged from a post hoc analysis of a trial that was not designed to treat HDL. Nonetheless, when the data were analyzed "a lower risk was seen among this subset of patients with LDL less than 70 mg/dL whose HDL levels were in the highest quintile." Dr. Cannon was not involved in the trial.
The findings, both Drs. Barter and Cannon agreed, come at time when interventions targeting HDL have had mixed results.
Statin therapy in addition to lowering LDL can achieve modest increases in HDL, Dr. Cannon said.
"Losing weight and exercise are effective life style interventions," Dr. Barter said, "and if everybody was lean we wouldn't have the current epidemic of cardiovascular disease. But not every patient can run."
Niacin can increase HDL by 30% to 40%, but the chemical flush associated with its use makes it difficult for many patients to tolerate.
Results have been somewhat better with extended release niacin, as well as with an investigational compound that combines niacin with laropiprant, a potent, highly selective prostaglandin antagonist. (See: ESC: Investigative Niacin Combo Turns Down the Heat on Flushing)
And trials of the most promising HDL-boosting drug, torcetrapib, were halted late last year when researchers discovered excess cardiovascular mortality among patients taking the drug. (See: ACC: Torcetrapib Studies Offer More Questions About HDL Booster)
Dr. Barter said he will be reporting data at the American Heart Association meeting in November that will answer some of the remaining questions about torcetrapib, which boosts HDL by 50% to 100% by inhibiting cholesteryl ester transfer protein (CTEP).
The investigators said the current trial was limited by a number of factors including the fact that patients defined by HDL quintiles were "not similar with respect to other cardiovascular risk factors and there may have been other differences that were not evaluated but that could have influenced the analysis." Two such missing pieces of information were waist circumference and insulin levels.
But for now, Dr. Barter said, "I would recommend HDL modifying regimens such as niacin for any [dyslipidemia] patient who has achieved a low LDL but who has not increased their HDL [to 55 mg/dL or higher]."
The TNT study was supported by Pfizer. Dr. Barter reported receiving financial support including grants, lecture fees, and consulting fees from Pfizer, AstraZeneca, and Merck. Dr. Cannon disclosed financial support from Merck, Schering Plough, Accumetrics, AstraZeneca, GlaxoSmithKline, Sanofi-aventis, and Bristol-Myers Squibb. Primary source: New England Journal of MedicineSource reference: Barter P et al "HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events" N Engl J Med 2007; 357: 1301-10
SYDNEY, Sept. 26 -- For patients with coronary artery disease, a maximum risk reduction required not only the lowest level of LDLs, but also the highest level of HDLs, found investigators here.
That assessment emerged from a post hoc analysis of the 9,770-patient TNT (Treating to New Targets) trial which found that at five years there were fewer deaths and non-fatal events among patients who achieved an LDL of less than 70 mg/dL and a mean HDL of 61.5 mg/dL (±10.1) after three months of statin therapy (P=0.03).
"In the univariate model, the event rate was reduced by 40% in the highest [HDL] quintile relative to the lowest," Philip Barter, M.D., of the Heart Research Institute in Sydney, and colleagues, reported the finding in the Sept. 27 issue of the New England Journal of Medicine. When the data were adjusted for covariates, in the entire TNT population there was a 25% reduction in risk (HR 0.75, 95% CI 0.60-0.95) for the highest HDL quintile versus the lowest (P=0.04).
Low HDL level was known to be a "powerful predictor of increased cardiovascular risk," but it had been argued that "if the LDL cholesterol level were reduced sufficiently, the level of HDL cholesterol might become irrelevant," they wrote.
"But we knew that even when LDL was aggressively treated, there was still a risk of events," Dr. Barter said in an interview. "This analysis confirms that clearly HDL remains important. If anything I am surprised by the magnitude of its importance. So the real message is that lower [LDL] is better, yes. But that is not enough to get rid of risk associated with low HDL."
The TNT randomized coronary disease patients who had a baseline LDL of 130 mg/dL or lower to 80 mg or 10 mg of atorvastatin (Lipitor). The target LDL was less than 70 mg/dL and patients were followed for five years. Patients in the high dose arm achieved a mean LDL of 77 mg/dL and reduced cardiovascular events by 22%. (See: ACC: LDL Cholesterol of Less than 80 mg/dL Reduces Risk of Heart Attack and Stroke)
In the current study, the investigators analyzed the relationship between HDL at the end of three months of statin therapy and time to first-event risk. The data were also stratified by LDL cholesterol level.
In an interview, Christopher Cannon, M.D., of Brigham and Women's Hospital and Harvard Medical School, agreed that the finding was "important," although he pointed out that it emerged from a post hoc analysis of a trial that was not designed to treat HDL. Nonetheless, when the data were analyzed "a lower risk was seen among this subset of patients with LDL less than 70 mg/dL whose HDL levels were in the highest quintile." Dr. Cannon was not involved in the trial.
The findings, both Drs. Barter and Cannon agreed, come at time when interventions targeting HDL have had mixed results.
Statin therapy in addition to lowering LDL can achieve modest increases in HDL, Dr. Cannon said.
"Losing weight and exercise are effective life style interventions," Dr. Barter said, "and if everybody was lean we wouldn't have the current epidemic of cardiovascular disease. But not every patient can run."
Niacin can increase HDL by 30% to 40%, but the chemical flush associated with its use makes it difficult for many patients to tolerate.
Results have been somewhat better with extended release niacin, as well as with an investigational compound that combines niacin with laropiprant, a potent, highly selective prostaglandin antagonist. (See: ESC: Investigative Niacin Combo Turns Down the Heat on Flushing)
And trials of the most promising HDL-boosting drug, torcetrapib, were halted late last year when researchers discovered excess cardiovascular mortality among patients taking the drug. (See: ACC: Torcetrapib Studies Offer More Questions About HDL Booster)
Dr. Barter said he will be reporting data at the American Heart Association meeting in November that will answer some of the remaining questions about torcetrapib, which boosts HDL by 50% to 100% by inhibiting cholesteryl ester transfer protein (CTEP).
The investigators said the current trial was limited by a number of factors including the fact that patients defined by HDL quintiles were "not similar with respect to other cardiovascular risk factors and there may have been other differences that were not evaluated but that could have influenced the analysis." Two such missing pieces of information were waist circumference and insulin levels.
But for now, Dr. Barter said, "I would recommend HDL modifying regimens such as niacin for any [dyslipidemia] patient who has achieved a low LDL but who has not increased their HDL [to 55 mg/dL or higher]."
The TNT study was supported by Pfizer. Dr. Barter reported receiving financial support including grants, lecture fees, and consulting fees from Pfizer, AstraZeneca, and Merck. Dr. Cannon disclosed financial support from Merck, Schering Plough, Accumetrics, AstraZeneca, GlaxoSmithKline, Sanofi-aventis, and Bristol-Myers Squibb. Primary source: New England Journal of MedicineSource reference: Barter P et al "HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events" N Engl J Med 2007; 357: 1301-10
No Link Between Thimerosal in Vaccines and Neuropsychological Harm
ATLANTA, Sept. 26 -- Children who were given thimerosal-containing vaccines or Rh globulins a decade ago showed no causal decline in neuropsychological outcomes by ages seven to 10, CDC researchers here found.
These findings suggested that the early exposure to thimerosal, an ethylmercury-containing preservative in vaccines, does not reduce neuropsychological functioning, William W. Thompson, Ph.D., of the CDC, and colleagues, reported in the Sept. 27 issue of the New England Journal of Medicine.
Among 42 neuropsychological tests assessed, only a few significant associations of any kind were identified, none important, the investigators found. The associations were small. Some were positive and some negative.
The findings came from a study of 1,047 children, seven to 10 years old, from four HMOs that participate in the CDC's Vaccine Safety Datalink.
Birthdates ranged from January 1993 through March 1997. The children were given standardized tests assessing 42 neuropsychological outcomes. However, autism-spectrum disorders were not assessed.
Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews.
The researchers assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first seven months of life.
The sources of prenatal exposure were flu vaccine, tetanus toxoid, hepatitis B vaccine, and thimerosal-containing Rh globulins.
Among the 42 neuropsychological outcomes, only a few significant associations with exposure to mercury-containing thimerosal were detected. These were small and almost equally divided between positive and negative effects, the researchers said.
For example, higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning.
Increasing levels of mercury exposure from birth to seven months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning.
Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination.
Tests of the interactions of mercury exposure from antibiotic use in the first seven months of life showed no consistent results, while tests of an interaction between prenatal and postnatal exposure also revealed no important differences.
Several studies of the effects of prenatal exposure to methyl mercury from fish consumption have shown certain negative associations, the researchers said.
However, they said that using methyl mercury as a referent for assessment of exposure to ethyl mercury from thimerosal is questionable, because the half-life of ethyl mercury in the blood is half that of methyl mercury.
Study limitations included the fact that a majority of the selected families declined to participate or could not be located so that the findings may have been influenced by selection bias.
In addition, they said, they were unable to control for interventions, such as speech therapy. Furthermore, information available for some potential confounding factors, such as family income, was imprecise.
Finally, the researchers wrote that the study did not examine the possible association between autism and exposure to mercury from vaccines and immune globulins.
The overall pattern of this study suggests that any significant associations may have been chance findings stemming from the large number of statistical tests performed, they concluded.
In an accompanying Perspective, Paul A. Offit, M.D., of Children's Hospital in Philadelphia, wrote that by choosing not to vaccinate children, parents elevate a now disproved risk above the real risk of being hospitalized or dying of influenza or other infection.
In recounting earlier thimerosal issues, he wrote that after much wrangling, on July 9, 1999, the CDC and the American Academy of Pediatrics asked pharmaceutical companies to remove thimerosal from vaccines as soon as possible and in the interim asked physicians to delay the birth dose of hepatitis B vaccine for children not at risk.
"The current levels of thimerosal will not hurt children," the Academy said, but "reducing these levels will make safe vaccines even safer." Critics wondered, Dr. Offit said, how removing something that had not been found unsafe could make vaccines safer, while many parents reasoned that thimerosal was targeted because it was harmful.
Clinicians were also confused, and some unprotected children died as a result of overwhelming infection.
Then beginning in 2000, parents founded several advocacy groups based on the belief that thimerosal had caused their children's autism, and a "cottage industry of charlatans offering false hope, partly in the form of mercury-chelating agents, was born," Dr. Offit said.
Despite several years of reassuring studies finding no association with autism or other neuropsychological outcomes, the thimerosal controversy continues to be emotionally charged. Thimerosal will probably be removed from flu vaccines and the controversy will settle down, Dr. Offit wrote.
"But the thimerosal controversy should stand as a cautionary tale of how not to communicate theoretical risks to the public," he wrote. Otherwise, he said, "the lesson inherent in the collateral damage caused by its precipitous removal will remain unlearned."
In a second Perspective, Stephen D. Sugarman, J.D., of the University of California at Berkeley, reviewed the legal battles now being waged over vaccines and autism and did not see an end to the litigation.
Although most experts have concluded that there is no proof of a causal tie between autism and thimerosal or the MMR vaccine, he wrote, some doctors and scientists, some groups representing families with autistic children, and many parents fervently believe there is a connection.
Not only do these families have support groups and organized lawyers behind them, but they also have the backing of several prominent senators and congressional representatives.
Whatever the outcome of the current lawsuits in the U.S. and Britain, it is unlikely that the battles over vaccines and autism will end, he concluded.
The study was supported by the CDC. The conclusions in this study are those of the authors and do not necessarily represent the views of the CDC.
Dr. Thompson reported being a former employee of Merck. Co-authors reported receiving consulting fees, lecture fees, and other forms or remuneration from Merck, Sanofi Pasteur, GlaxoSmithKline, MedImmune, Wyeth, Novartis, Abbott, and Aventis.
Co-author Lisa A. Jackson, M.D., reported serving as a consultant to the FDA Vaccines and Related Biological Products Advisory Committee; Tracy A. Lieu, M.D., reported serving as a consultant to the CDC Advisory Committee on Immunization Practices.
Dr. Offit, author of an accompanying Perspective, reported serving on the scientific advisory board of Merck and being the co-inventor of the bovine-human reassortant rotavirus vaccine RotaTeq, on which he holds a patent.
Mr. Sugarman, author of the other Perspective, reported no financial conflicts.Primary source: New England Journal of MedicineSource reference: Thompson, WW, et al "Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years" N Engl J Med 2007; 357: 1281-1292. Additional source: New England Journal of MedicineSource reference: Offit PA "Thimerosal and Vaccines-A Cautionary Tale" N Engl J Med 2007; 357: 1278-1279. Additional source: New England Journal of MedicineSource reference: Sugarman SD "Cases in Vaccine Court-Legal battles over Vaccines and Autism" N Engl J Med 2007; 357: 1275-1277.
ATLANTA, Sept. 26 -- Children who were given thimerosal-containing vaccines or Rh globulins a decade ago showed no causal decline in neuropsychological outcomes by ages seven to 10, CDC researchers here found.
These findings suggested that the early exposure to thimerosal, an ethylmercury-containing preservative in vaccines, does not reduce neuropsychological functioning, William W. Thompson, Ph.D., of the CDC, and colleagues, reported in the Sept. 27 issue of the New England Journal of Medicine.
Among 42 neuropsychological tests assessed, only a few significant associations of any kind were identified, none important, the investigators found. The associations were small. Some were positive and some negative.
The findings came from a study of 1,047 children, seven to 10 years old, from four HMOs that participate in the CDC's Vaccine Safety Datalink.
Birthdates ranged from January 1993 through March 1997. The children were given standardized tests assessing 42 neuropsychological outcomes. However, autism-spectrum disorders were not assessed.
Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews.
The researchers assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first seven months of life.
The sources of prenatal exposure were flu vaccine, tetanus toxoid, hepatitis B vaccine, and thimerosal-containing Rh globulins.
Among the 42 neuropsychological outcomes, only a few significant associations with exposure to mercury-containing thimerosal were detected. These were small and almost equally divided between positive and negative effects, the researchers said.
For example, higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning.
Increasing levels of mercury exposure from birth to seven months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning.
Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination.
Tests of the interactions of mercury exposure from antibiotic use in the first seven months of life showed no consistent results, while tests of an interaction between prenatal and postnatal exposure also revealed no important differences.
Several studies of the effects of prenatal exposure to methyl mercury from fish consumption have shown certain negative associations, the researchers said.
However, they said that using methyl mercury as a referent for assessment of exposure to ethyl mercury from thimerosal is questionable, because the half-life of ethyl mercury in the blood is half that of methyl mercury.
Study limitations included the fact that a majority of the selected families declined to participate or could not be located so that the findings may have been influenced by selection bias.
In addition, they said, they were unable to control for interventions, such as speech therapy. Furthermore, information available for some potential confounding factors, such as family income, was imprecise.
Finally, the researchers wrote that the study did not examine the possible association between autism and exposure to mercury from vaccines and immune globulins.
The overall pattern of this study suggests that any significant associations may have been chance findings stemming from the large number of statistical tests performed, they concluded.
In an accompanying Perspective, Paul A. Offit, M.D., of Children's Hospital in Philadelphia, wrote that by choosing not to vaccinate children, parents elevate a now disproved risk above the real risk of being hospitalized or dying of influenza or other infection.
In recounting earlier thimerosal issues, he wrote that after much wrangling, on July 9, 1999, the CDC and the American Academy of Pediatrics asked pharmaceutical companies to remove thimerosal from vaccines as soon as possible and in the interim asked physicians to delay the birth dose of hepatitis B vaccine for children not at risk.
"The current levels of thimerosal will not hurt children," the Academy said, but "reducing these levels will make safe vaccines even safer." Critics wondered, Dr. Offit said, how removing something that had not been found unsafe could make vaccines safer, while many parents reasoned that thimerosal was targeted because it was harmful.
Clinicians were also confused, and some unprotected children died as a result of overwhelming infection.
Then beginning in 2000, parents founded several advocacy groups based on the belief that thimerosal had caused their children's autism, and a "cottage industry of charlatans offering false hope, partly in the form of mercury-chelating agents, was born," Dr. Offit said.
Despite several years of reassuring studies finding no association with autism or other neuropsychological outcomes, the thimerosal controversy continues to be emotionally charged. Thimerosal will probably be removed from flu vaccines and the controversy will settle down, Dr. Offit wrote.
"But the thimerosal controversy should stand as a cautionary tale of how not to communicate theoretical risks to the public," he wrote. Otherwise, he said, "the lesson inherent in the collateral damage caused by its precipitous removal will remain unlearned."
In a second Perspective, Stephen D. Sugarman, J.D., of the University of California at Berkeley, reviewed the legal battles now being waged over vaccines and autism and did not see an end to the litigation.
Although most experts have concluded that there is no proof of a causal tie between autism and thimerosal or the MMR vaccine, he wrote, some doctors and scientists, some groups representing families with autistic children, and many parents fervently believe there is a connection.
Not only do these families have support groups and organized lawyers behind them, but they also have the backing of several prominent senators and congressional representatives.
Whatever the outcome of the current lawsuits in the U.S. and Britain, it is unlikely that the battles over vaccines and autism will end, he concluded.
The study was supported by the CDC. The conclusions in this study are those of the authors and do not necessarily represent the views of the CDC.
Dr. Thompson reported being a former employee of Merck. Co-authors reported receiving consulting fees, lecture fees, and other forms or remuneration from Merck, Sanofi Pasteur, GlaxoSmithKline, MedImmune, Wyeth, Novartis, Abbott, and Aventis.
Co-author Lisa A. Jackson, M.D., reported serving as a consultant to the FDA Vaccines and Related Biological Products Advisory Committee; Tracy A. Lieu, M.D., reported serving as a consultant to the CDC Advisory Committee on Immunization Practices.
Dr. Offit, author of an accompanying Perspective, reported serving on the scientific advisory board of Merck and being the co-inventor of the bovine-human reassortant rotavirus vaccine RotaTeq, on which he holds a patent.
Mr. Sugarman, author of the other Perspective, reported no financial conflicts.Primary source: New England Journal of MedicineSource reference: Thompson, WW, et al "Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years" N Engl J Med 2007; 357: 1281-1292. Additional source: New England Journal of MedicineSource reference: Offit PA "Thimerosal and Vaccines-A Cautionary Tale" N Engl J Med 2007; 357: 1278-1279. Additional source: New England Journal of MedicineSource reference: Sugarman SD "Cases in Vaccine Court-Legal battles over Vaccines and Autism" N Engl J Med 2007; 357: 1275-1277.
Increase in Nosocomial S. aureus Infection Documented
CHICAGO, Sept. 26 -- The incidence and economic burden of hospital-acquired Staphylococcus aureus infections have increased significantly in recent years, investigators here have concluded.
From 1998 to 2003 the rate of nosocomial S. aureus infection increased by 7.1% to 11% annually across differ types of hospital stays, Gary Noskin, M.D., of Northwestern University, and colleagues, reported online ahead of the November issue of Clinical Infectious Diseases.
The largest cumulative overall increase in the S. aureus infection rate over the six years was 53.5% among patients hospitalized for invasive orthopedic stays.
The findings emerged from attempt to clarify current trends in nosocomial S. aureus infection by retrospectively reviewing data from the Agency for Healthcare Research and Quality Nationwide Inpatient Sample. With about seven million hospital stays annually, the Nationwide Inpatient Sample is the nation's largest all-payer inpatient database.
During the same 1998 to 2003 period the economic burden of S. aureus infection in hospitals increased from 9.2% to 17.9%, reaching an estimated $14.5 billion in 2003 for all inpatient stays. The findings reflect a pressing need to implement and adhere to CDC guidelines related to nosocomial infections, they asserted.
Despite the increased rate of infection, mortality attributable to S. aureus decreased during the follow-up period.
"The observed decrease in in-hospital mortality risk may be associated with the introduction of more stringent infection-control programs or with appropriate early treatment of [methicillin-resistant S. aureus] infections with vancomycin," the authors said. "There are very limited data on the impact of S. aureus infections on in-hospital mortality with which to compare our results."
The study and findings grew out of a background of growing concern about the increasing rate of MRSA infections. For example, a report from the National Nosocomial Infectious Surveillance System indicated that the rate of antimicrobial resistance among ICU patients with S. aureus infection increased by 40% in 1999 compared with 1994-1998.
A report from the Canadian Nosocomial Infection Surveillance Program indicated that the rate of MRSA infections increased more than 10-fold from 1995 to 2003 (0.46 cases/1,000 admissions versus 5.1 cases/1,000 admissions). Similar disquieting evidence has emerged from studies in Europe and most other regions of the world, the authors noted.
In the current study, the percentage of patients with S. aureus-related infection at discharge increased from 0.74% in 1998 to 1.0% in 2003, representing an annual increase of 7.1% (P=0.004 for trend). The incidence of S. aureus-infection associated with surgical stays increased from 0.90% to 1.3%, a 7.9% annual change (P=0.001). The infection rate associated with invasive orthopedic stays increased from 1.2% to 1.8%, an annual rate of change of 9.3% (P<0.001).
The S. aureus infection rate among patients with invasive neurosurgical stays did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (P=0.034).
The annual economic burden of nosocomial S. aureus infection increased significantly over the six-year period (P<0.05). In 2003 the estimated total economic burden of S. aureus infection associated with surgical stays was $12.3 billion.
Mortality associated with nosocomial S. aureus infection decreased from 7.1% to 5.6%, representing an annual decline of 4.6% (P=0.001). For surgical stays, S. aureus-attributable mortality decreased from 7.1% to 5.5%, an annual decline of 4.6% (P=0.002).
Dr. Noskin and colleagues said that the results highlight the need to implement the Joint Commission's National Hospital Patient Safety Goal No. 7 for 2007: to reduce the risk of health care-associated infection. The Joint Commission recommends "complying with current CDC hand-hygiene guidelines and managing as sentinel events all identified cases of unanticipated death or major permanent loss of function associated with a health-care associated infection."
The study was funded by 3M Medical. Some of the study's coauthors are 3M employees, and several others disclosed received research and grant support from 3M. Primary source: Clinical Infectious DiseasesSource reference: Noskin GA et al. "National trends in Staphylococcus aureus infection rates: impact on economic burden and mortality over a 6-year period (1998-2003). Clin Infect Dis 2007; 45: epub.
CHICAGO, Sept. 26 -- The incidence and economic burden of hospital-acquired Staphylococcus aureus infections have increased significantly in recent years, investigators here have concluded.
From 1998 to 2003 the rate of nosocomial S. aureus infection increased by 7.1% to 11% annually across differ types of hospital stays, Gary Noskin, M.D., of Northwestern University, and colleagues, reported online ahead of the November issue of Clinical Infectious Diseases.
The largest cumulative overall increase in the S. aureus infection rate over the six years was 53.5% among patients hospitalized for invasive orthopedic stays.
The findings emerged from attempt to clarify current trends in nosocomial S. aureus infection by retrospectively reviewing data from the Agency for Healthcare Research and Quality Nationwide Inpatient Sample. With about seven million hospital stays annually, the Nationwide Inpatient Sample is the nation's largest all-payer inpatient database.
During the same 1998 to 2003 period the economic burden of S. aureus infection in hospitals increased from 9.2% to 17.9%, reaching an estimated $14.5 billion in 2003 for all inpatient stays. The findings reflect a pressing need to implement and adhere to CDC guidelines related to nosocomial infections, they asserted.
Despite the increased rate of infection, mortality attributable to S. aureus decreased during the follow-up period.
"The observed decrease in in-hospital mortality risk may be associated with the introduction of more stringent infection-control programs or with appropriate early treatment of [methicillin-resistant S. aureus] infections with vancomycin," the authors said. "There are very limited data on the impact of S. aureus infections on in-hospital mortality with which to compare our results."
The study and findings grew out of a background of growing concern about the increasing rate of MRSA infections. For example, a report from the National Nosocomial Infectious Surveillance System indicated that the rate of antimicrobial resistance among ICU patients with S. aureus infection increased by 40% in 1999 compared with 1994-1998.
A report from the Canadian Nosocomial Infection Surveillance Program indicated that the rate of MRSA infections increased more than 10-fold from 1995 to 2003 (0.46 cases/1,000 admissions versus 5.1 cases/1,000 admissions). Similar disquieting evidence has emerged from studies in Europe and most other regions of the world, the authors noted.
In the current study, the percentage of patients with S. aureus-related infection at discharge increased from 0.74% in 1998 to 1.0% in 2003, representing an annual increase of 7.1% (P=0.004 for trend). The incidence of S. aureus-infection associated with surgical stays increased from 0.90% to 1.3%, a 7.9% annual change (P=0.001). The infection rate associated with invasive orthopedic stays increased from 1.2% to 1.8%, an annual rate of change of 9.3% (P<0.001).
The S. aureus infection rate among patients with invasive neurosurgical stays did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (P=0.034).
The annual economic burden of nosocomial S. aureus infection increased significantly over the six-year period (P<0.05). In 2003 the estimated total economic burden of S. aureus infection associated with surgical stays was $12.3 billion.
Mortality associated with nosocomial S. aureus infection decreased from 7.1% to 5.6%, representing an annual decline of 4.6% (P=0.001). For surgical stays, S. aureus-attributable mortality decreased from 7.1% to 5.5%, an annual decline of 4.6% (P=0.002).
Dr. Noskin and colleagues said that the results highlight the need to implement the Joint Commission's National Hospital Patient Safety Goal No. 7 for 2007: to reduce the risk of health care-associated infection. The Joint Commission recommends "complying with current CDC hand-hygiene guidelines and managing as sentinel events all identified cases of unanticipated death or major permanent loss of function associated with a health-care associated infection."
The study was funded by 3M Medical. Some of the study's coauthors are 3M employees, and several others disclosed received research and grant support from 3M. Primary source: Clinical Infectious DiseasesSource reference: Noskin GA et al. "National trends in Staphylococcus aureus infection rates: impact on economic burden and mortality over a 6-year period (1998-2003). Clin Infect Dis 2007; 45: epub.
Current Chemotherapy Regimens Prolong Colorectal Cancer Survival
September 26, 2007 — Newer chemotherapy regimens are providing patients with advanced colorectal cancer clear, incremental benefits in delaying disease progression and prolonging survival, researchers say. However, the benefits of multidrug combinations come at a cost, researchers warn in the September 20 Online First issue of The Lancet Oncology. Among the drawbacks are increased toxicities.
"More data are needed to balance the benefits of the best newer regimens against their potential toxicity," senior author John Ioannidis, MD, from the University of Ioannina School of Medicine in Greece told Medscape Oncology. "Our meta analysis identifies which regimens are currently the best and which comparisons lack sufficient data," he added. "It can therefore be used in guiding the design of future trials."
Dr. Ioannidis said his research team had expected to see progress in the field and had sought to quantify these advances. "Our results can be used for building recommendations for the treatment of advanced colorectal cancer with a more accurate understanding of how much benefit can be attained with each regimen," he said.
For years, fluorouracil had been the mainstay of systemic treatment of colorectal cancer, though the overall benefit in survival was reportedly small. Attempts to improve survival led to the biochemical modulation of fluorouracil, mainly by leucovorin, which offered an added modest survival advantage. Newer chemotherapy drugs, such as irinotecan and oxaliplatin, and molecular-targeted agents, such as bevacizumab and cetuximab, have also shown effectiveness in trials of patients with advanced colorectal cancer.
Newer Regimens Providing Incremental Benefits
The investigators studied 242 randomized trials to compare systemic treatment regimens conducted during the last 40 years. The team categorized treatment by fluorouracil-based regimens, irinotecan, oxaliplatin, bevacizumab, and cetuximab.
The research team used multiple-treatment meta-analysis methodology to combine information from direct comparisons such as treatments compared within a randomized trial and indirect comparisons such as treatments compared between trials.
The primary endpoint for the study was death, and the secondary endpoint was progression of disease. The researchers used Monte Carlo simulations to establish what regimen offered the most benefit for these endpoints. They conducted analyzes of all trials and studied trials separately that looked at first-line treatments and non–first-line treatments.
The trials included a total of 56,677 patients and involved 137 different chemotherapy regimens. The researchers found that irinotecan, oxaliplatin, and molecular-targeted treatments prolong survival for patients with advanced colorectal cancer by several months vs a few years ago when these treatments were unavailable.
The investigators report that for patients who would be expected to live for 1 year while taking fluorouracil and leucovorin, the estimated absolute survival benefit of additional treatment with irinotecan and bevacizumab was 8 months. Benefits of survival were also noted for the addition of oxaliplatin and bevacizumab or irinotecan and oxaliplatin; they observed a prolongation of 4.7 months for each regimen.
Improving Survival but Increasing Dangerous Adverse Events as Well
The regimen of fluorouracil, leucovorin, irinotecan, and bevacizumab, which has the highest probability to be the best in improving survival according to the analysis, might be complicated by up to 84.9% of grade 3 or 4 adverse events, the study authors warn, including a 1.5% chance of perforation of the gastrointestinal tract.
Dr. Ioannidis pointed out a number of limitations to the study. "The analysis depends on results that have been publicly available," he told Medscape Oncology. "It may therefore be affected by publication bias against negative results for specific regimens."
New drugs are currently being tested, and another limitation of the analysis involves gaps in available data. For example, the study authors include considerable information on bevacizumab, but less on cetuximab. However, they anticipate that additional evidence will become available during the next few years.
Dr. Ioannidis and his team note that at least 2 other trials have presented preliminary data on the combination of cetuximab with oxaliplatin and fluorouracil with leucovorin in abstracts, but no mature survival or progression data are currently available.
They add that a phase 3 trial for panitumumab has shown encouraging results as a second-line treatment against best supportive care, but it was also not eligible for the present meta-analysis, and more evidence for this drug will likely be published soon.
"Our meta-analysis concludes that progress has definitely been made in this area of research," the study authors write, "but the existing uncertainties suggest that more data are needed especially for the newest regimens."
The study authors have disclosed no relevant financial relationships.
Lancet Oncol. Published online September 20, 2007.
September 26, 2007 — Newer chemotherapy regimens are providing patients with advanced colorectal cancer clear, incremental benefits in delaying disease progression and prolonging survival, researchers say. However, the benefits of multidrug combinations come at a cost, researchers warn in the September 20 Online First issue of The Lancet Oncology. Among the drawbacks are increased toxicities.
"More data are needed to balance the benefits of the best newer regimens against their potential toxicity," senior author John Ioannidis, MD, from the University of Ioannina School of Medicine in Greece told Medscape Oncology. "Our meta analysis identifies which regimens are currently the best and which comparisons lack sufficient data," he added. "It can therefore be used in guiding the design of future trials."
Dr. Ioannidis said his research team had expected to see progress in the field and had sought to quantify these advances. "Our results can be used for building recommendations for the treatment of advanced colorectal cancer with a more accurate understanding of how much benefit can be attained with each regimen," he said.
For years, fluorouracil had been the mainstay of systemic treatment of colorectal cancer, though the overall benefit in survival was reportedly small. Attempts to improve survival led to the biochemical modulation of fluorouracil, mainly by leucovorin, which offered an added modest survival advantage. Newer chemotherapy drugs, such as irinotecan and oxaliplatin, and molecular-targeted agents, such as bevacizumab and cetuximab, have also shown effectiveness in trials of patients with advanced colorectal cancer.
Newer Regimens Providing Incremental Benefits
The investigators studied 242 randomized trials to compare systemic treatment regimens conducted during the last 40 years. The team categorized treatment by fluorouracil-based regimens, irinotecan, oxaliplatin, bevacizumab, and cetuximab.
The research team used multiple-treatment meta-analysis methodology to combine information from direct comparisons such as treatments compared within a randomized trial and indirect comparisons such as treatments compared between trials.
The primary endpoint for the study was death, and the secondary endpoint was progression of disease. The researchers used Monte Carlo simulations to establish what regimen offered the most benefit for these endpoints. They conducted analyzes of all trials and studied trials separately that looked at first-line treatments and non–first-line treatments.
The trials included a total of 56,677 patients and involved 137 different chemotherapy regimens. The researchers found that irinotecan, oxaliplatin, and molecular-targeted treatments prolong survival for patients with advanced colorectal cancer by several months vs a few years ago when these treatments were unavailable.
The investigators report that for patients who would be expected to live for 1 year while taking fluorouracil and leucovorin, the estimated absolute survival benefit of additional treatment with irinotecan and bevacizumab was 8 months. Benefits of survival were also noted for the addition of oxaliplatin and bevacizumab or irinotecan and oxaliplatin; they observed a prolongation of 4.7 months for each regimen.
Improving Survival but Increasing Dangerous Adverse Events as Well
The regimen of fluorouracil, leucovorin, irinotecan, and bevacizumab, which has the highest probability to be the best in improving survival according to the analysis, might be complicated by up to 84.9% of grade 3 or 4 adverse events, the study authors warn, including a 1.5% chance of perforation of the gastrointestinal tract.
Dr. Ioannidis pointed out a number of limitations to the study. "The analysis depends on results that have been publicly available," he told Medscape Oncology. "It may therefore be affected by publication bias against negative results for specific regimens."
New drugs are currently being tested, and another limitation of the analysis involves gaps in available data. For example, the study authors include considerable information on bevacizumab, but less on cetuximab. However, they anticipate that additional evidence will become available during the next few years.
Dr. Ioannidis and his team note that at least 2 other trials have presented preliminary data on the combination of cetuximab with oxaliplatin and fluorouracil with leucovorin in abstracts, but no mature survival or progression data are currently available.
They add that a phase 3 trial for panitumumab has shown encouraging results as a second-line treatment against best supportive care, but it was also not eligible for the present meta-analysis, and more evidence for this drug will likely be published soon.
"Our meta-analysis concludes that progress has definitely been made in this area of research," the study authors write, "but the existing uncertainties suggest that more data are needed especially for the newest regimens."
The study authors have disclosed no relevant financial relationships.
Lancet Oncol. Published online September 20, 2007.
FDA Issues Public Health Advisory for Fentora
Yael Waknine
September 26, 2007 — The US Food and Drug Administration has issued a public health advisory today to alert healthcare professionals and consumers regarding reports of life-threatening and sometimes fatal events in patients receiving fentanyl buccal tablets (Fentora, Cephalon, Inc).
These events were associated with improper patient selection (eg, opioid-intolerant patients or patients who did not have cancer), improper dosing (incorrect dose or dose too high), and/or improper product substitution for nonequianalgesic fentanyl-containing products.
Physicians and other healthcare professionals are strongly advised to follow product labeling when prescribing fentanyl buccal tablets to minimize the risk for respiratory depression.
Fentanyl buccal tablets are indicated only for the management of breakthrough pain in opioid-tolerant cancer patients. Patients considered physiologically opioid tolerant are those who have been taking at least 60 mg of oral morphine per day, 25 µg of transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for 1 week or longer.
Opioid-intolerant patients and those with acute pain, postoperative pain, headache/migraine, or sports injuries should not receive this medication.
Patients must be under a physician's care and be closely supervised during treatment. In addition, physicians should make careful dose adjustments for breakthrough pain, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.
Because the buccal tablet formulation results in higher blood levels of fentanyl, conversion from fentanyl citrate transmucosal lozenges (Actiq, Cephalon) must include a dose reduction. Treatment with 200- or 400-µg lozenges is equivalent to a 100-µg fentanyl buccal tablet, a 600- or 800-µg lozenge is equivalent to a 200-µg buccal tablet, and treatment with a 1200- or 1600-µg lozenge is equivalent to a 400-µg buccal tablet.
For opioid-tolerant patients receiving any other around-the-clock opioids for breakthrough cancer pain, the initial dose for fentanyl buccal tablets is 100 µg. During titration and after dose selection, no more than 2 fentanyl buccal tablets should be taken per episode of breakthrough pain and 4 hours must elapse prior to treating the next episode.
Healthcare professionals and patients/caregivers should be aware of symptoms associated with fentanyl overdose that require immediate medical attention, such as trouble breathing or shallow breathing; tiredness; extreme sleepiness or sedation; inability to think, talk, or walk normally; and feeling faint, dizzy, or confused.
Yael Waknine
September 26, 2007 — The US Food and Drug Administration has issued a public health advisory today to alert healthcare professionals and consumers regarding reports of life-threatening and sometimes fatal events in patients receiving fentanyl buccal tablets (Fentora, Cephalon, Inc).
These events were associated with improper patient selection (eg, opioid-intolerant patients or patients who did not have cancer), improper dosing (incorrect dose or dose too high), and/or improper product substitution for nonequianalgesic fentanyl-containing products.
Physicians and other healthcare professionals are strongly advised to follow product labeling when prescribing fentanyl buccal tablets to minimize the risk for respiratory depression.
Fentanyl buccal tablets are indicated only for the management of breakthrough pain in opioid-tolerant cancer patients. Patients considered physiologically opioid tolerant are those who have been taking at least 60 mg of oral morphine per day, 25 µg of transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for 1 week or longer.
Opioid-intolerant patients and those with acute pain, postoperative pain, headache/migraine, or sports injuries should not receive this medication.
Patients must be under a physician's care and be closely supervised during treatment. In addition, physicians should make careful dose adjustments for breakthrough pain, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.
Because the buccal tablet formulation results in higher blood levels of fentanyl, conversion from fentanyl citrate transmucosal lozenges (Actiq, Cephalon) must include a dose reduction. Treatment with 200- or 400-µg lozenges is equivalent to a 100-µg fentanyl buccal tablet, a 600- or 800-µg lozenge is equivalent to a 200-µg buccal tablet, and treatment with a 1200- or 1600-µg lozenge is equivalent to a 400-µg buccal tablet.
For opioid-tolerant patients receiving any other around-the-clock opioids for breakthrough cancer pain, the initial dose for fentanyl buccal tablets is 100 µg. During titration and after dose selection, no more than 2 fentanyl buccal tablets should be taken per episode of breakthrough pain and 4 hours must elapse prior to treating the next episode.
Healthcare professionals and patients/caregivers should be aware of symptoms associated with fentanyl overdose that require immediate medical attention, such as trouble breathing or shallow breathing; tiredness; extreme sleepiness or sedation; inability to think, talk, or walk normally; and feeling faint, dizzy, or confused.
Men who smoke risk erectile dysfunction: study
Wed Sep 26, 2:22 PM ET
Otherwise healthy men who smoke risk developing erectile dysfunction -- and the more cigarettes they smoke, the greater the risk of erectile dysfunction, according to a new study.
Erectile dysfunction is the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. In a study of 4,763 Chinese men aged 35 to 74 years who were free of blood vessel disease and who reported that they had been sexually active within the last 6 months, the researchers found a significant statistical link between the number of cigarettes smoked and the likelihood of erectile dysfunction.
"The association between cigarette smoking and erectile dysfunction was found in earlier studies," said first author Dr. Jiang He of Tulane University School of Public Health, New Orleans. "However, most of those studies were conducted in patients with hypertension (high blood pressure), diabetes and cardiovascular disease. What distinguishes this study is that it is the first to find this association among healthy men."
Overall, men who smoked had a 41-percent greater risk of erectile dysfunction than men who did not, the team reports in the American Journal of Epidemiology.
And there was a clear "dose-response" relationship, meaning that the more the men smoked, the higher was their risk of erectile dysfunction. Compared with non-smokers, men who smoked up to 10 cigarettes per day had a 27-percent greater likelihood of erectile dysfunction ; those who smoked 11 to 20 butts a day had a 45-percent greater likelihood of erectile dysfunction; and those who smoked more than 20 cigarettes daily had a-65 percent greater chance of suffering erectile dysfunction.
The investigators estimate that 22.7 percent of erectile all dysfunction cases among healthy Chinese men - or 11.8 million cases -- might be caused by cigarette smoking.
And even when cigarette smokers quit, their risk of developing erectile dysfunction did not decrease. The risk of erectile dysfunction was statistically about the same for former cigarette smokers as for current cigarette smokers, the authors found.
"This study really has a strong message for young men," He said. "It may get their attention if they know that smoking is associated with erectile dysfunction -- even in the healthy population."
"So the message is: Don't start."
SOURCE: American Journal of Epidemiology, October 1, 2007.
Wed Sep 26, 2:22 PM ET
Otherwise healthy men who smoke risk developing erectile dysfunction -- and the more cigarettes they smoke, the greater the risk of erectile dysfunction, according to a new study.
Erectile dysfunction is the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. In a study of 4,763 Chinese men aged 35 to 74 years who were free of blood vessel disease and who reported that they had been sexually active within the last 6 months, the researchers found a significant statistical link between the number of cigarettes smoked and the likelihood of erectile dysfunction.
"The association between cigarette smoking and erectile dysfunction was found in earlier studies," said first author Dr. Jiang He of Tulane University School of Public Health, New Orleans. "However, most of those studies were conducted in patients with hypertension (high blood pressure), diabetes and cardiovascular disease. What distinguishes this study is that it is the first to find this association among healthy men."
Overall, men who smoked had a 41-percent greater risk of erectile dysfunction than men who did not, the team reports in the American Journal of Epidemiology.
And there was a clear "dose-response" relationship, meaning that the more the men smoked, the higher was their risk of erectile dysfunction. Compared with non-smokers, men who smoked up to 10 cigarettes per day had a 27-percent greater likelihood of erectile dysfunction ; those who smoked 11 to 20 butts a day had a 45-percent greater likelihood of erectile dysfunction; and those who smoked more than 20 cigarettes daily had a-65 percent greater chance of suffering erectile dysfunction.
The investigators estimate that 22.7 percent of erectile all dysfunction cases among healthy Chinese men - or 11.8 million cases -- might be caused by cigarette smoking.
And even when cigarette smokers quit, their risk of developing erectile dysfunction did not decrease. The risk of erectile dysfunction was statistically about the same for former cigarette smokers as for current cigarette smokers, the authors found.
"This study really has a strong message for young men," He said. "It may get their attention if they know that smoking is associated with erectile dysfunction -- even in the healthy population."
"So the message is: Don't start."
SOURCE: American Journal of Epidemiology, October 1, 2007.
Three drinks a day ups breast cancer risk: study
By Michael KahnThu Sep 27, 2:09 AM ET
Three or more drinks a day, whether beer, wine or spirits, boost a woman's risk of breast cancer as much as smoking a pack of cigarettes, U.S. researchers said on Thursday.
The relationship between alcohol and breast cancer is known but there has been little data on whether the choice of drink made a difference, they told a European Cancer Conference.
In what the researchers said was one of the largest studies to investigate links between breast cancer and alcohol -- found that alcohol itself and the amount a person consumed were key rather than the type of drink.
"Studies have consistently linked drinking alcohol to an increased risk of female breast cancer, but until now there has been little data, most of it conflicting, about an independent role played by the choice of beverage type," Arthur Klatsky of Kaiser Permanente in California and one of the researchers said.
Breast cancer is the second most common cancer killer of women, after lung cancer. It will be diagnosed in 1.2 million people globally this year and will kill 500,000.
Other studies have shown that light- to moderate alcohol use can protect against heart attacks, though Klatsky said other mechanisms were probably at work.
The heart protection likely comes from alcohol-induced "good" cholesterol, reduced blood clotting and decreased diabetes risk. But for breast cancer, the ethyl alcohol found in all booze likely ups the risk, the researchers said.
The researchers looked at the drinking habits of more than 70,000 women from a variety of ethnic backgrounds who supplied information during health examinations between 1978 and 1985. By 2004, nearly 3,000 of the women were diagnosed with breast cancer.
Among women who drank, the team examined a preference for a type of alcohol and how much of each drink people consumed. They also compared the total amount consumed and compared it to women who drank less than one drink a day.
Women who drank between one and two alcoholic drinks per day increased their risk of breast cancer by 10 percent compared with people who consumed less than one drink each day, the study found. The risk of breast cancer jumped by 30 percent in women who drank more than three drinks a day.
The results were also similar in different age and ethnic groups, the researchers said.
By Michael KahnThu Sep 27, 2:09 AM ET
Three or more drinks a day, whether beer, wine or spirits, boost a woman's risk of breast cancer as much as smoking a pack of cigarettes, U.S. researchers said on Thursday.
The relationship between alcohol and breast cancer is known but there has been little data on whether the choice of drink made a difference, they told a European Cancer Conference.
In what the researchers said was one of the largest studies to investigate links between breast cancer and alcohol -- found that alcohol itself and the amount a person consumed were key rather than the type of drink.
"Studies have consistently linked drinking alcohol to an increased risk of female breast cancer, but until now there has been little data, most of it conflicting, about an independent role played by the choice of beverage type," Arthur Klatsky of Kaiser Permanente in California and one of the researchers said.
Breast cancer is the second most common cancer killer of women, after lung cancer. It will be diagnosed in 1.2 million people globally this year and will kill 500,000.
Other studies have shown that light- to moderate alcohol use can protect against heart attacks, though Klatsky said other mechanisms were probably at work.
The heart protection likely comes from alcohol-induced "good" cholesterol, reduced blood clotting and decreased diabetes risk. But for breast cancer, the ethyl alcohol found in all booze likely ups the risk, the researchers said.
The researchers looked at the drinking habits of more than 70,000 women from a variety of ethnic backgrounds who supplied information during health examinations between 1978 and 1985. By 2004, nearly 3,000 of the women were diagnosed with breast cancer.
Among women who drank, the team examined a preference for a type of alcohol and how much of each drink people consumed. They also compared the total amount consumed and compared it to women who drank less than one drink a day.
Women who drank between one and two alcoholic drinks per day increased their risk of breast cancer by 10 percent compared with people who consumed less than one drink each day, the study found. The risk of breast cancer jumped by 30 percent in women who drank more than three drinks a day.
The results were also similar in different age and ethnic groups, the researchers said.
Subscribe to:
Posts (Atom)