Low-dose aspirin doesn't protect women against overall cognitive decline, a finding that adds to doubts about whether anti-inflammatory drugs offer any neuroprotective benefit.
Among more than 6,000 healthy women who took low-dose aspirin or placebo for a decade, there were no significant between-group differences in overall cognitive function, rate of cognitive decline, or risk for serious decline, reported Jae Hee Kang, Sc.D., of Brigham and Women's Hospital here, and colleagues.
"In this study, we observed no apparent benefit of low-dose aspirin in slowing cognitive decline over four years," the authors wrote online in BMJ. "Other methods for preserving cognitive function in older people need to be investigated."
Women who took aspirin had a 20% lower risk for decline in category fluency, the authors noted, but the effect seen with this secondary endpoint was not enough to tip the scales in aspirin's favor.
Earlier this week, two other NSAIDs were shown to offer no protective benefit against Alzheimer's, investigators reported online in Neurology. Neither naproxen (Aleve) nor celecoxib (Celebrex) reduced the risk of developing Alzheimer's, at least in the short term, found researchers in the ADAPT (Alzheimer's Disease Anti-inflammatory Prevention Trial) study
According to results of the randomized ADAPT study funded by the National Institute on Aging, there was even a suggestion that both naproxen and celecoxib were associated with a slightly increased risk of dementia.
Interest in the use of NSAIDs for Alzheimer's prevention was sparked by a study, published in Neurology in 1993, indicating that indomethacin in doses of 100 to 150 mg/day appeared to protect mild-to-moderately impaired Alzheimer's patients from the degree of cognitive decline exhibited by well-matched controls.
But results from randomized trials conducted since have been inconclusive or have shown no neuroprotective benefit for the NSAIDs rofecoxib, naproxen, nimesulide, and diclofenac, the ADAPT investigators noted.
Saturday, April 28, 2007
F.D.A. Turns Down Merck Arthritis Drug
The Food and Drug Administration has rejected Merck & Company’s bid to win approval for a successor to Vioxx, the arthritis medication that Merck withdrew from the market more than two years ago, the company said yesterday.
The decision had been widely expected ever since a panel of F.D.A. advisers voted two weeks ago by 20 to 1 against approval of the drug, Arcoxia, because of concerns that it could cause as many as 30,000 heart attacks a year if widely used.
Like Vioxx, whose name has become almost synonymous with drug safety problems, Arcoxia is among a class of anti-inflammatory drugs called cox-2 inhibitors. Such medications were developed in the hope that they would be less likely to cause stomach bleeding than ibuprofen and naproxen.
But while they did prove to safeguard the stomach, they have been linked to heart risks. Merck withdrew Vioxx in September 2004 after research showed that it doubled the risk of heart attacks and strokes.
Despite the safety concerns in the United States, Arcoxia is on sale in 63 other countries. It brought in revenue of $265 million last year.
The decision had been widely expected ever since a panel of F.D.A. advisers voted two weeks ago by 20 to 1 against approval of the drug, Arcoxia, because of concerns that it could cause as many as 30,000 heart attacks a year if widely used.
Like Vioxx, whose name has become almost synonymous with drug safety problems, Arcoxia is among a class of anti-inflammatory drugs called cox-2 inhibitors. Such medications were developed in the hope that they would be less likely to cause stomach bleeding than ibuprofen and naproxen.
But while they did prove to safeguard the stomach, they have been linked to heart risks. Merck withdrew Vioxx in September 2004 after research showed that it doubled the risk of heart attacks and strokes.
Despite the safety concerns in the United States, Arcoxia is on sale in 63 other countries. It brought in revenue of $265 million last year.
Depression May Be Early Sign of Parkinson's Disease
FRIDAY, April 27 (HealthDay News) -- In some cases, depression can be an early manifestation of Parkinson's disease, new research suggests.
Researchers at the Harvard School of Public Health compared antidepressant use among more than 1,000 individuals with Parkinson's disease to more than 6,600 age- and gender-matched individuals without the degenerative neurological illness.
They found that people currently on antidepressants had an 80 percent higher risk of developing Parkinson's disease than those who had never taken antidepressants. This was true for both men and women, regardless of age or the class of antidepressant used.
"We think this is not actually the medication that is causing Parkinson's disease. Instead, we think people who are going to get Parkinson's disease get depression first," said study co-author Dr. Alvaro Alonso, a research associate at Harvard. "It's very important not to say that people taking antidepressants have a higher risk of developing Parkinson's disease," he said.
That's because the effect was only apparent in the year prior to disease diagnosis, and because it was true for two different types of medications, tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), which work via wholly different mechanisms, Alonso explained.
He noted that additional data, not included in the published study, indicated that newer users of antidepressants -- those who had been on the drugs for less than one year -- had a threefold higher risk of developing Parkinson's than people who had never used antidepressants.
Alonso's interpretation: Depressive symptoms could be one of the first manifestations of Parkinson's disease.
The research is scheduled to be presented May 1 at the annual meeting of the American Academy of Neurology, in Boston.
Dr. Rajesh Pahwa, director of the Parkinson Disease and Movement Disorder Center at the University of Kansas Medical Center, in Kansas City, called the observation "interesting."
At the same time, he said, the depression-Parkinson's link is "common knowledge" among neurologists, who have long recognized that depression often occurs alongside Parkinson's disease.
Researchers at the Harvard School of Public Health compared antidepressant use among more than 1,000 individuals with Parkinson's disease to more than 6,600 age- and gender-matched individuals without the degenerative neurological illness.
They found that people currently on antidepressants had an 80 percent higher risk of developing Parkinson's disease than those who had never taken antidepressants. This was true for both men and women, regardless of age or the class of antidepressant used.
"We think this is not actually the medication that is causing Parkinson's disease. Instead, we think people who are going to get Parkinson's disease get depression first," said study co-author Dr. Alvaro Alonso, a research associate at Harvard. "It's very important not to say that people taking antidepressants have a higher risk of developing Parkinson's disease," he said.
That's because the effect was only apparent in the year prior to disease diagnosis, and because it was true for two different types of medications, tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), which work via wholly different mechanisms, Alonso explained.
He noted that additional data, not included in the published study, indicated that newer users of antidepressants -- those who had been on the drugs for less than one year -- had a threefold higher risk of developing Parkinson's than people who had never used antidepressants.
Alonso's interpretation: Depressive symptoms could be one of the first manifestations of Parkinson's disease.
The research is scheduled to be presented May 1 at the annual meeting of the American Academy of Neurology, in Boston.
Dr. Rajesh Pahwa, director of the Parkinson Disease and Movement Disorder Center at the University of Kansas Medical Center, in Kansas City, called the observation "interesting."
At the same time, he said, the depression-Parkinson's link is "common knowledge" among neurologists, who have long recognized that depression often occurs alongside Parkinson's disease.
Friday, April 27, 2007
Depressive Symptoms May Be Linked to Risk for Incident Diabetes in Older Adults
April 26, 2007 — Compared with their peers, older adults who report high levels of depressive symptoms — whether these symptoms occur once, increase, or persist — have a higher risk of developing type 2 diabetes, according to results of a 10-year study. The risk for incident diabetes among the study participants, who were part of the Cardiovascular Health Study (CHS), was independent of other risk factors. The study is published in the April 23 issue of the Archives of Internal Medicine.
Lead author Mercedes R. Carnethon, PhD, from Northwestern University in Chicago, Illinois, told Medscape the main finding was that, in addition to older adults who had a single report of high depressive symptoms, those whose depressive symptoms worsened were more likely to develop diabetes, as were those who had persistently high symptoms of depression.
She explained that most previous studies suggesting that depressive symptoms are linked with risk of developing diabetes looked at younger populations and were based on a single self-report of depression and a single measurement of factors related to depression and diabetes. Because of the episodic nature of depressive symptoms, a single self-report might not fully characterize the relationship between depression and diabetes.
The authors aimed to test the hypothesis that high depressive symptoms were linked with incident diabetes in adults 65 years and older by investigating single and multiple reports of depression and repeated measurements of related factors. They write that to their knowledge, theirs is the only study to look at this relationship in older adults, a population known to have a high prevalence of diabetes and depression.
The study population comprised participants in the CHS, a prospective, population-based, cohort study of cardiovascular disease in adults 65 years and older. The 4681 participants in the current study had complete data and no diabetes at baseline. They were examined yearly from baseline (1989 or 1990) to 1999.
At each annual examination, participants filled in a 10-item Center for Epidemiologic Studies–Depression Scale (CES-D) questionnaire, which measures depressive symptoms during the previous week. The questions deal with mood (5 questions), irritability (1 question), calories/energy (2 questions), concentration (1 question), and sleep (1 question). They are scored from 0 (rarely) to 3 (most of the time) for a maximum of 30 points.
The researchers looked at 3 measures of high depressive symptoms: baseline CES-D of 8 or higher (high score), increase in CES-D of 5 points or higher (increasing score), and 2 consecutive CES-D scores of 8 or higher (persistently high score).
The participants' annual examination also included clinical measures of height and weight (used to calculate body mass index), as well as blood tests to determine levels of C-reactive protein and fasting glucose. New-onset diabetes was defined as the initiation of therapy for diabetes or having a high fasting blood glucose level.
Lead author Mercedes R. Carnethon, PhD, from Northwestern University in Chicago, Illinois, told Medscape the main finding was that, in addition to older adults who had a single report of high depressive symptoms, those whose depressive symptoms worsened were more likely to develop diabetes, as were those who had persistently high symptoms of depression.
She explained that most previous studies suggesting that depressive symptoms are linked with risk of developing diabetes looked at younger populations and were based on a single self-report of depression and a single measurement of factors related to depression and diabetes. Because of the episodic nature of depressive symptoms, a single self-report might not fully characterize the relationship between depression and diabetes.
The authors aimed to test the hypothesis that high depressive symptoms were linked with incident diabetes in adults 65 years and older by investigating single and multiple reports of depression and repeated measurements of related factors. They write that to their knowledge, theirs is the only study to look at this relationship in older adults, a population known to have a high prevalence of diabetes and depression.
The study population comprised participants in the CHS, a prospective, population-based, cohort study of cardiovascular disease in adults 65 years and older. The 4681 participants in the current study had complete data and no diabetes at baseline. They were examined yearly from baseline (1989 or 1990) to 1999.
At each annual examination, participants filled in a 10-item Center for Epidemiologic Studies–Depression Scale (CES-D) questionnaire, which measures depressive symptoms during the previous week. The questions deal with mood (5 questions), irritability (1 question), calories/energy (2 questions), concentration (1 question), and sleep (1 question). They are scored from 0 (rarely) to 3 (most of the time) for a maximum of 30 points.
The researchers looked at 3 measures of high depressive symptoms: baseline CES-D of 8 or higher (high score), increase in CES-D of 5 points or higher (increasing score), and 2 consecutive CES-D scores of 8 or higher (persistently high score).
The participants' annual examination also included clinical measures of height and weight (used to calculate body mass index), as well as blood tests to determine levels of C-reactive protein and fasting glucose. New-onset diabetes was defined as the initiation of therapy for diabetes or having a high fasting blood glucose level.
U.S. PSYCH: Insomnia Treatment Boosts Antidepressant Efficacy
SAN FRANCISCO, April 25 -- A significant number of patients with major depression also suffer from chronic insomnia that hampers recovery, a sleep expert said here.
"Treating the insomnia pharmacologically or behaviorally can improve outcomes in depression," said Christopher L. Drake, Ph.D., of the Henry Ford Hospital Sleep Disorders and Research Center in Detroit.
The prevalence of insomnia comorbid with psychiatric disorders is 40.4%, with major depression accounting for about 15%, he said in a presentation at the U.S. Psychiatric and Mental Health Congress regional extension meeting here.
Depression treatment itself may increase the risk of sleep disturbance. A 2002 study in the Journal of Clinical Psychopharmacology found that 15% to 25% of patients on a selective serotonin reuptake inhibitor antidepressant had insomnia as an adverse event while 15% to 20% reported somnolence during double-blind acute treatment.
"Insomnia is the most common 'residual' symptom in non-remitted depression," Dr. Drake said, so there may be some independence between insomnia and depression. But, residual symptoms such as insomnia predict time to relapse or recurrence of depression among responders.
Poor sleep quality is also predictive of suicidal behavior.
However, most insomniacs do not seek treatment for the condition. In a study by the Gallup Organization, only 6% of individuals with insomnia had seen a physician with sleep problems as the primary reason for consultation while 24% had insomnia as a secondary reason for consultation.
Sleep aids do appear to work for patients with major depression, though. A 1999 study of zolpidem (Ambien) found it improved time to sleep onset and waking after sleep onset among patients with stable SSRI-treated depression.
Furthermore, treating insomnia in patients with major depressive disorder improves antidepressant response, Dr. Drake said.
In a study published in the journal Biological Psychiatry in 2006, patients who took both the sleep aid eszopiclone (Lunesta) and fluoxetine (Prozac) had an antidepressant response about two weeks earlier than patients treated with fluoxetine alone (P=0.0002).
Eszopiclone and fluoxetine together also significantly improved on both the overall Hamilton depression scores and Hamilton scores excluding insomnia-related items compared to fluoxetine alone. Significantly more patients treated for both depression and insomnia reached remission as well (42% versus 32.8%, P=0.03).
While there are few controlled trials of treatment of comorbid insomnia among patients with other psychiatric and medical conditions, there is some evidence of benefit for those with mixed psychiatric conditions, alcoholism, post-traumatic stress disorder, and Alzheimer's disease, according to a study in the journal Sleep Medicine Reviews last year.
"Treating the insomnia pharmacologically or behaviorally can improve outcomes in depression," said Christopher L. Drake, Ph.D., of the Henry Ford Hospital Sleep Disorders and Research Center in Detroit.
The prevalence of insomnia comorbid with psychiatric disorders is 40.4%, with major depression accounting for about 15%, he said in a presentation at the U.S. Psychiatric and Mental Health Congress regional extension meeting here.
Depression treatment itself may increase the risk of sleep disturbance. A 2002 study in the Journal of Clinical Psychopharmacology found that 15% to 25% of patients on a selective serotonin reuptake inhibitor antidepressant had insomnia as an adverse event while 15% to 20% reported somnolence during double-blind acute treatment.
"Insomnia is the most common 'residual' symptom in non-remitted depression," Dr. Drake said, so there may be some independence between insomnia and depression. But, residual symptoms such as insomnia predict time to relapse or recurrence of depression among responders.
Poor sleep quality is also predictive of suicidal behavior.
However, most insomniacs do not seek treatment for the condition. In a study by the Gallup Organization, only 6% of individuals with insomnia had seen a physician with sleep problems as the primary reason for consultation while 24% had insomnia as a secondary reason for consultation.
Sleep aids do appear to work for patients with major depression, though. A 1999 study of zolpidem (Ambien) found it improved time to sleep onset and waking after sleep onset among patients with stable SSRI-treated depression.
Furthermore, treating insomnia in patients with major depressive disorder improves antidepressant response, Dr. Drake said.
In a study published in the journal Biological Psychiatry in 2006, patients who took both the sleep aid eszopiclone (Lunesta) and fluoxetine (Prozac) had an antidepressant response about two weeks earlier than patients treated with fluoxetine alone (P=0.0002).
Eszopiclone and fluoxetine together also significantly improved on both the overall Hamilton depression scores and Hamilton scores excluding insomnia-related items compared to fluoxetine alone. Significantly more patients treated for both depression and insomnia reached remission as well (42% versus 32.8%, P=0.03).
While there are few controlled trials of treatment of comorbid insomnia among patients with other psychiatric and medical conditions, there is some evidence of benefit for those with mixed psychiatric conditions, alcoholism, post-traumatic stress disorder, and Alzheimer's disease, according to a study in the journal Sleep Medicine Reviews last year.
Aspirin Doesn't Prevent Cognitive Decline in Older Women
Low-dose aspirin does not prevent cognitive decline in older women, researchers report in BMJ.
The study included a subset of the participants in the Women's Health Study, a double-blind, placebo-controlled trial of aspirin's role in the primary prevention of cardiovascular disease and cancer. Researchers followed some 6400 women aged 65 or older and in generally good health for a mean of almost 10 years. The women underwent three cognitive assessments via telephone at 2-year intervals, beginning an average of almost 6 years after randomization.
At follow-up, global scores of cognitive function — based on tests of verbal memory, general cognition, and category fluency — did not differ between groups. The only cognitive advantage the aspirin group held over those on placebo occurred in category fluency (in which participants were asked to name as many animals as they could within a minute), a result that the authors say should be interpreted cautiously.
They conclude that "other methods for preserving cognitive function in older people need to be investigated."
The study included a subset of the participants in the Women's Health Study, a double-blind, placebo-controlled trial of aspirin's role in the primary prevention of cardiovascular disease and cancer. Researchers followed some 6400 women aged 65 or older and in generally good health for a mean of almost 10 years. The women underwent three cognitive assessments via telephone at 2-year intervals, beginning an average of almost 6 years after randomization.
At follow-up, global scores of cognitive function — based on tests of verbal memory, general cognition, and category fluency — did not differ between groups. The only cognitive advantage the aspirin group held over those on placebo occurred in category fluency (in which participants were asked to name as many animals as they could within a minute), a result that the authors say should be interpreted cautiously.
They conclude that "other methods for preserving cognitive function in older people need to be investigated."
Thursday, April 26, 2007
Forget NSAIDs for Alzheimer's Prevention
BALTIMORE, April 25 -- Neither naproxen (Aleve) nor celecoxib (Celebrex) reduced the risk of developing Alzheimer's disease, at least in the short term, investigators from the suspended ADAPT trial reported.
According to results of the randomized study funded by the National Institute on Aging, there was even a suggestion that both naproxen and celecoxib were associated with a slightly increased risk of dementia, reported Constantine Lyketsos, M.D., M.H.S., of Johns Hopkins, and colleagues in the ADAPT trial.
The findings run counter to those of earlier observational studies suggesting that chronic use of NSAIDs could help to prevent Alzheimer's and other forms of dementia, the investigators reported in an online release from the May 22 issue of Neurology.
"Although our study was conducted to test the hypothesis that celecoxib or naproxen would reduce the incidence of Alzheimer's disease, these results indicate no such effect, at least within the first few years after treatment begins," said Dr. Lyketsos.
The ADAPT (Alzheimer's Disease Anti-inflammatory Prevention Trial) study was halted in December of 2004, after investigators in a different trial (the Adenoma Prevention with Celecoxib study) announced that the drug was associated with significantly increased cardiovascular risk.
Interest in the use of NSAIDs for Alzheimer's prevention was sparked by a study, published in Neurology in 1993, indicating that indomethacin in doses of 100 to 150 mg/day appeared to protect mild-to-moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by well-matched controls, Dr. Lyketsos and colleagues noted.
"However, several subsequent trials have shown no benefit from treatment of Alzheimer's disease with rofecoxib, naproxen, nimesulide, or diclofenac," they wrote. "A trial of rofecoxib to prevent progression to Alzheimer's disease in those with mild cognitive impairment (often a prodromal phase of Alzheimer's disease) was similarly disappointing."
The ADAPT study was designed to test the hypothesis that NSAIDs might be able to protect cognitively normal people against the depredations of Alzheimer's.
The study was a randomized, placebo-controlled, double-masked clinical trial at six U.S. dementia research clinics. The participants were volunteers 70 and older who were considered cognitively normal, with cognitive screening scores above designated cutoffs, and a family history of Alzheimer's disease.
Beginning in early 2001, the patients were randomized to celecoxib at 200 mg twice daily, naproxen sodium at 220 mg twice daily, or placebo. The main outcome measure was a diagnosis of Alzheimer's after randomization.
Patients with possible cognitive syndromes were identified with the Cognitive Assessment Battery, and returned for a dementia evaluation conducted by physicians, trained study nurses, and psychometrists, who conducted physical, neurologic, and mental status exams, and a detailed psychometric assessment battery.
The authors included in their analysis all events that occurred up to July 17, 2005, six months after the study was halted.
They found that "neither treatment was associated with reduction in the incidence of Alzheimer's disease, all cause-dementia, or the Alzheimer's disease prodromes. Instead, there was a suggestion of increase in the incidence of Alzheimer's disease with both treatments."
According to results of the randomized study funded by the National Institute on Aging, there was even a suggestion that both naproxen and celecoxib were associated with a slightly increased risk of dementia, reported Constantine Lyketsos, M.D., M.H.S., of Johns Hopkins, and colleagues in the ADAPT trial.
The findings run counter to those of earlier observational studies suggesting that chronic use of NSAIDs could help to prevent Alzheimer's and other forms of dementia, the investigators reported in an online release from the May 22 issue of Neurology.
"Although our study was conducted to test the hypothesis that celecoxib or naproxen would reduce the incidence of Alzheimer's disease, these results indicate no such effect, at least within the first few years after treatment begins," said Dr. Lyketsos.
The ADAPT (Alzheimer's Disease Anti-inflammatory Prevention Trial) study was halted in December of 2004, after investigators in a different trial (the Adenoma Prevention with Celecoxib study) announced that the drug was associated with significantly increased cardiovascular risk.
Interest in the use of NSAIDs for Alzheimer's prevention was sparked by a study, published in Neurology in 1993, indicating that indomethacin in doses of 100 to 150 mg/day appeared to protect mild-to-moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by well-matched controls, Dr. Lyketsos and colleagues noted.
"However, several subsequent trials have shown no benefit from treatment of Alzheimer's disease with rofecoxib, naproxen, nimesulide, or diclofenac," they wrote. "A trial of rofecoxib to prevent progression to Alzheimer's disease in those with mild cognitive impairment (often a prodromal phase of Alzheimer's disease) was similarly disappointing."
The ADAPT study was designed to test the hypothesis that NSAIDs might be able to protect cognitively normal people against the depredations of Alzheimer's.
The study was a randomized, placebo-controlled, double-masked clinical trial at six U.S. dementia research clinics. The participants were volunteers 70 and older who were considered cognitively normal, with cognitive screening scores above designated cutoffs, and a family history of Alzheimer's disease.
Beginning in early 2001, the patients were randomized to celecoxib at 200 mg twice daily, naproxen sodium at 220 mg twice daily, or placebo. The main outcome measure was a diagnosis of Alzheimer's after randomization.
Patients with possible cognitive syndromes were identified with the Cognitive Assessment Battery, and returned for a dementia evaluation conducted by physicians, trained study nurses, and psychometrists, who conducted physical, neurologic, and mental status exams, and a detailed psychometric assessment battery.
The authors included in their analysis all events that occurred up to July 17, 2005, six months after the study was halted.
They found that "neither treatment was associated with reduction in the incidence of Alzheimer's disease, all cause-dementia, or the Alzheimer's disease prodromes. Instead, there was a suggestion of increase in the incidence of Alzheimer's disease with both treatments."
1/3 of sexually active older adults with HIV/AIDs has unprotected sex
Findings suggest more prevention efforts may be needed
ATHENS, Ohio (April 24, 2007) -- One out of three sexually active older adults infected with HIV has unprotected sex, according to a study by Ohio University researchers. A survey of 260 HIV-positive older adults found that of those having sex, most were male, took Viagra and were in a relationship.
AIDs cases among the over-50 crowd reached 90,000 in 2003. According to the Centers for Disease Control and Prevention, they will account for half of all HIV/AIDS cases in the United States by 2015 because medical intervention has extended the lifespan of those infected with HIV. Additionally, drugs such as Viagra have made it possible for older adults to remain sexually active longer.
Past studies have shown that up to 65 percent of older adults ages 60 to 71 have sexual intercourse. Among older adults who are HIV-positive, according to the Ohio University findings, 38 percent are sexually active.
“Those who are more likely to engage in riskier behavior – for example, those who are using drugs – are more likely to have unprotected sex,” said graduate student Travis Lovejoy, who led the study along with Ohio University health psychologist Timothy Heckman. “What we don’t know yet is whether these individuals are in a monogamous relationship with someone else who is HIV positive and believe there is no risk of infection.”
The study also found that sexual activity was more prevalent among HIV-positive older adults who were not cognitively impaired, were younger and who considered their overall health to be good.
Because many older adults with HIV are not sexually active, those who do have unprotected sex account for just 13 percent of the overall number of infected people who are aged 50 or older. However, one-third of those who are sexually active have unprotected sex, which suggests that prevention efforts may need to be more highly targeted toward these individuals.
The behavioral information was pulled from a survey of 260 HIV-positive older adults who were participating in a study examining support groups. The study was funded by a three-year, $1.8 million grant from the National Institute of Mental Health and the National Institute of Nursing Research.
Lovejoy presented the findings at the annual conference of the Society of Behavioral Medicine in March.
ATHENS, Ohio (April 24, 2007) -- One out of three sexually active older adults infected with HIV has unprotected sex, according to a study by Ohio University researchers. A survey of 260 HIV-positive older adults found that of those having sex, most were male, took Viagra and were in a relationship.
AIDs cases among the over-50 crowd reached 90,000 in 2003. According to the Centers for Disease Control and Prevention, they will account for half of all HIV/AIDS cases in the United States by 2015 because medical intervention has extended the lifespan of those infected with HIV. Additionally, drugs such as Viagra have made it possible for older adults to remain sexually active longer.
Past studies have shown that up to 65 percent of older adults ages 60 to 71 have sexual intercourse. Among older adults who are HIV-positive, according to the Ohio University findings, 38 percent are sexually active.
“Those who are more likely to engage in riskier behavior – for example, those who are using drugs – are more likely to have unprotected sex,” said graduate student Travis Lovejoy, who led the study along with Ohio University health psychologist Timothy Heckman. “What we don’t know yet is whether these individuals are in a monogamous relationship with someone else who is HIV positive and believe there is no risk of infection.”
The study also found that sexual activity was more prevalent among HIV-positive older adults who were not cognitively impaired, were younger and who considered their overall health to be good.
Because many older adults with HIV are not sexually active, those who do have unprotected sex account for just 13 percent of the overall number of infected people who are aged 50 or older. However, one-third of those who are sexually active have unprotected sex, which suggests that prevention efforts may need to be more highly targeted toward these individuals.
The behavioral information was pulled from a survey of 260 HIV-positive older adults who were participating in a study examining support groups. The study was funded by a three-year, $1.8 million grant from the National Institute of Mental Health and the National Institute of Nursing Research.
Lovejoy presented the findings at the annual conference of the Society of Behavioral Medicine in March.
New hereditary breast cancer gene discovered
A new hereditary breast cancer gene has been discovered by scientists at the Lundberg Laboratory for Cancer Research and the Plastic Surgery Clinic at the Sahlgrenska Academy in Sweden. The researchers found that women with a certain hereditary deformity syndrome run a nearly twenty times higher risk of contracting breast cancer than expected.
Several research teams around the world have long been searching for new hereditary breast cancer genes, but thus far few have been found.
"Our findings are extremely important, providing new knowledge of hereditary cancer genes and how they can cause breast cancer. The discovery also makes it possible to uncover breast cancer in women who have a predisposition for Saethre-Chotzen malformation syndrome," says Göran Stenman.
By detailed mapping of families with Saethre-Chotzen syndrome, the Göteborg scientists have now found that women with this syndrome have an elevated risk of contracting breast cancer. Saethre-Chotzen is a syndrome that primarily involves malformations of the skull, face, hands, and feet. The syndrome is caused by mutations in a gene called TWIST1.
"Our findings show that women with this syndrome run a nearly twenty times greater risk of contracting breast cancer than expected. Moreover, many of the women were young when they were affected by breast cancer," says Göran Stenman.
The findings of the study show that women with this syndrome should be receive early mammograms in order to discover breast cancer at an early stage.
"We have already started to use this new knowledge in our work with patients and now recommend regular mammograms for young women with this syndrome. Several early cases of breast cancer have already been uncovered with mammography," says Pelle Sahlin, chief physician at the Plastic Surgery Clinic.
The scientists are now going to perform various experiments to chart the mechanism of how TWIST1 increases the risk of breast cancer. Studies are also under way to find out what proportion of cases of hereditary breast cancer are caused by mutations in the TWIST1 gene.
Several research teams around the world have long been searching for new hereditary breast cancer genes, but thus far few have been found.
"Our findings are extremely important, providing new knowledge of hereditary cancer genes and how they can cause breast cancer. The discovery also makes it possible to uncover breast cancer in women who have a predisposition for Saethre-Chotzen malformation syndrome," says Göran Stenman.
By detailed mapping of families with Saethre-Chotzen syndrome, the Göteborg scientists have now found that women with this syndrome have an elevated risk of contracting breast cancer. Saethre-Chotzen is a syndrome that primarily involves malformations of the skull, face, hands, and feet. The syndrome is caused by mutations in a gene called TWIST1.
"Our findings show that women with this syndrome run a nearly twenty times greater risk of contracting breast cancer than expected. Moreover, many of the women were young when they were affected by breast cancer," says Göran Stenman.
The findings of the study show that women with this syndrome should be receive early mammograms in order to discover breast cancer at an early stage.
"We have already started to use this new knowledge in our work with patients and now recommend regular mammograms for young women with this syndrome. Several early cases of breast cancer have already been uncovered with mammography," says Pelle Sahlin, chief physician at the Plastic Surgery Clinic.
The scientists are now going to perform various experiments to chart the mechanism of how TWIST1 increases the risk of breast cancer. Studies are also under way to find out what proportion of cases of hereditary breast cancer are caused by mutations in the TWIST1 gene.
Wednesday, April 25, 2007
Oats Cut Cholesterol, But Evidence for Whole Grains Lags
Whole-grain oats can carry the lipid-lowering banner higher than other whole grains -- but not too high.
So found a Cochrane review by Sarah Kelly, Ph.D., of the University of Teesside here, and colleagues. They reported that observational studies have made the case for the beneficial effects of whole grains against coronary heart disease risk factors, but clinical trials have lagged behind.
The trials have provided evidence for LDL reduction only by whole-grain oats, and even then only in the short term, the Cochrane group found in a meta-analysis.
Whole-grain oats significantly lowered total (-0.20 mmol/L, P=0.0001) and low-density lipoprotein cholesterol (-0.18 mmol/L, P<0.0001) over four to eight weeks, the investigators said.
"There is enough evidence for whole grain oats to suggest that healthcare professionals could recommend oats as part of cholesterol-reduction programs," they wrote.
However, they cautioned that despite the consistency of the whole grain oats findings, the 10 trials were short, of poor quality, underpowered, and funded by companies that stood to gain from the results.
"There is a need for well-designed, adequately powered, longer term randomized controlled studies in this area," they wrote. "In particular there is a need for randomized controlled trials on wholegrain foods and diets other than oats."
The authors acknowledged several epidemiological studies that have examined the association between the intake of wholegrain foods and the risk for coronary heart disease: The Iowa Women's Health study, reported in 1999, found greater intake of whole grains associated with reduced risk of death from coronary heart disease. In the same year, the Nurses' Health Study indicated wholegrain intake lowered risk of developing coronary heart disease.
In 2003 the Atherosclerosis Risk in Communities (ARIC) study showed whole grain consumption reduced risk of overall mortality and coronary artery disease incidence. And in 2002, the Framingham Offspring Study found diets rich in whole grains inversely associated with total cholesterol, LDL cholesterol and body mass index.
So found a Cochrane review by Sarah Kelly, Ph.D., of the University of Teesside here, and colleagues. They reported that observational studies have made the case for the beneficial effects of whole grains against coronary heart disease risk factors, but clinical trials have lagged behind.
The trials have provided evidence for LDL reduction only by whole-grain oats, and even then only in the short term, the Cochrane group found in a meta-analysis.
Whole-grain oats significantly lowered total (-0.20 mmol/L, P=0.0001) and low-density lipoprotein cholesterol (-0.18 mmol/L, P<0.0001) over four to eight weeks, the investigators said.
"There is enough evidence for whole grain oats to suggest that healthcare professionals could recommend oats as part of cholesterol-reduction programs," they wrote.
However, they cautioned that despite the consistency of the whole grain oats findings, the 10 trials were short, of poor quality, underpowered, and funded by companies that stood to gain from the results.
"There is a need for well-designed, adequately powered, longer term randomized controlled studies in this area," they wrote. "In particular there is a need for randomized controlled trials on wholegrain foods and diets other than oats."
The authors acknowledged several epidemiological studies that have examined the association between the intake of wholegrain foods and the risk for coronary heart disease: The Iowa Women's Health study, reported in 1999, found greater intake of whole grains associated with reduced risk of death from coronary heart disease. In the same year, the Nurses' Health Study indicated wholegrain intake lowered risk of developing coronary heart disease.
In 2003 the Atherosclerosis Risk in Communities (ARIC) study showed whole grain consumption reduced risk of overall mortality and coronary artery disease incidence. And in 2002, the Framingham Offspring Study found diets rich in whole grains inversely associated with total cholesterol, LDL cholesterol and body mass index.
Study shows food preparation may play a bigger role in chronic disease than was previously thought
How your food is cooked may be as important to your health as the food itself. Researchers now know more about a new class of toxins that might soon become as important a risk factor for heart disease and metabolic disorders as trans fats.
This class of toxins, called advanced glycation end products (AGEs), are absorbed into the body through the consumption of grilled, fried, or broiled animal products, such as meats and cheeses. AGEs, which are also produced when food products are sterilized and pasteurized, have been linked to inflammation, insulin resistance, diabetes, vascular and kidney disease, and Alzheimer’s disease.
A new study at Mount Sinai School of Medicine reveals that AGE levels are elevated in the blood of healthy people, and even more so in older individuals than in younger people. Of particular interest was the finding that a major determinant of the blood levels of AGEs is the amount of AGEs in the diet, not dietary calories, sugar, or fat. The study, which was done in collaboration with, and supported by, the National Institute on Aging (NIA), is published in the April issue of the Journal of Gerontology: Medical Sciences.
"AGEs are quite deceptive, since they also give our food desirable tastes and smells," says Helen Vlassara, MD, senior study author, Director of the Division of Experimental Diabetes and Aging, and Professor of Medicine and Geriatrics at Mount Sinai School of Medicine. "So, consuming high amounts of grilled, broiled, or fried food means consuming significant amounts of AGEs, and AGEs in excess are toxic. People should be given information about their AGE intake and be advised to consider their intake in the same way they would think about their trans fats and salt intake. They should be warned about their AGE levels the way they are about their cholesterol levels or cigarette smoking."
Inflammation and oxidative stress are more common in older age, so the goal of the study was to assess whether AGEs played a significant role in age-related inflammation and oxidative stress by measuring AGE levels in both young and older individuals. The study involved 172 healthy men and women who were divided into two age groups—those between the ages of 18 and 45 and those between the ages of 60 and 80. Dr. Vlassara and her team also wanted to assess whether AGE levels correlated with dietary intake. To do this, her team recorded the patient’s body weight, body fat, three-day dietary information, and collected blood samples to measure biomarkers of inflammation, such as C-reactive protein (CRP). Blood samples were used to test for two common AGEs, called carboxymethyllysine (CML) and methylglyoxal (MG), which latch on to proteins and fats.
This class of toxins, called advanced glycation end products (AGEs), are absorbed into the body through the consumption of grilled, fried, or broiled animal products, such as meats and cheeses. AGEs, which are also produced when food products are sterilized and pasteurized, have been linked to inflammation, insulin resistance, diabetes, vascular and kidney disease, and Alzheimer’s disease.
A new study at Mount Sinai School of Medicine reveals that AGE levels are elevated in the blood of healthy people, and even more so in older individuals than in younger people. Of particular interest was the finding that a major determinant of the blood levels of AGEs is the amount of AGEs in the diet, not dietary calories, sugar, or fat. The study, which was done in collaboration with, and supported by, the National Institute on Aging (NIA), is published in the April issue of the Journal of Gerontology: Medical Sciences.
"AGEs are quite deceptive, since they also give our food desirable tastes and smells," says Helen Vlassara, MD, senior study author, Director of the Division of Experimental Diabetes and Aging, and Professor of Medicine and Geriatrics at Mount Sinai School of Medicine. "So, consuming high amounts of grilled, broiled, or fried food means consuming significant amounts of AGEs, and AGEs in excess are toxic. People should be given information about their AGE intake and be advised to consider their intake in the same way they would think about their trans fats and salt intake. They should be warned about their AGE levels the way they are about their cholesterol levels or cigarette smoking."
Inflammation and oxidative stress are more common in older age, so the goal of the study was to assess whether AGEs played a significant role in age-related inflammation and oxidative stress by measuring AGE levels in both young and older individuals. The study involved 172 healthy men and women who were divided into two age groups—those between the ages of 18 and 45 and those between the ages of 60 and 80. Dr. Vlassara and her team also wanted to assess whether AGE levels correlated with dietary intake. To do this, her team recorded the patient’s body weight, body fat, three-day dietary information, and collected blood samples to measure biomarkers of inflammation, such as C-reactive protein (CRP). Blood samples were used to test for two common AGEs, called carboxymethyllysine (CML) and methylglyoxal (MG), which latch on to proteins and fats.
Tuesday, April 24, 2007
AHA-ATVB: No Early Benefit Seen to Drug-Eluting Stents Over CABG
Drug-eluting stents may not offer the early advantage over coronary artery bypass grafts (CABG) seen with bare-metal devices, researchers reported here.
In a single-center observational study, drug-eluting stents and CABG had similar 30-day and three-year outcomes for coronary patients, said James M. Wilson, M.D., of the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston, and colleagues.
The study, presented at the American Heart Association's Conference on Arteriosclerosis, Thrombosis, and Vascular Biology here, represented one of the first reports on outcomes of drug-eluting stents versus bypass grafting.
In previous studies, bare-metal stents had better outcomes at one year that then eroded to equivalence at three years and disadvantage compared with CABG at long-term follow-up, Dr. Wilson said.
"It's a little worrisome that we don't have that early advantage we had with the bare-metal stents," he said. "This surprised us."
Dr. Wilson and colleagues looked at in-hospital and three-year follow-up data from 1,598 unselected coronary-artery patients who underwent isolated primary revascularization by drug-eluting stents or CABG.
Patients were case matched by procedure propensity score to ensure similar patient characteristics between groups. For both, the average age was 64, about 7% had an urgent procedure, about 30% had diabetes, and about 75% had more than one diseased vessel.
Early, 30-day major adverse cardiac and cerebrovascular event findings were:
Similar overall (3.78% CABG versus 5.01% DES, P=NS).
Not significantly different for myocardial infarction between groups (1.67% versus 2.22%, P=NS).
Significantly lower stroke rate with drug eluting stents (1.11% versus 0.11%, P<0.01).
Similar for 30-day mortality (1.67% versus 2.22%, P=NS).
Identical target vessel and target lesion revascularization rates by CABG (0.11% versus 0.11%, P=NS).
Significantly different target vessel and target lesion revascularization rates by drug eluting stents between groups (0.00% versus 1.78%, P<0.01).
For mid-term outcomes, the researchers looked at mortality at three years post-revascularization. They found no statistically significant difference between CABG and drug eluting stents (6.6% versus 9.0%, P=NS).
While drug-eluting stents were expected to offer advantages over bare-metal stents, overconfidence in patient selection appears to have erased any advantage, Dr. Wilson concluded.
"With drug-eluting stents, the data from randomized trials was so exciting I think we began to treat the more difficult lesions with hopes of long-term success," he said.
An FDA advisory panel concluded late last year that drug-eluting stents are safe and effective when used as indicated in stable patients with single-vessel disease. An estimated 60% of the six-million drug-eluting stents implanted worldwide are used off-label in complex lesions and high-risk patients.
"We have a stent that has a reduced likelihood of failure long term but the patients we've chosen to put them in have given away the early advantage," Dr. Wilson said. "If we were to use our patient selection criteria that we used for bare metal stents our outcomes might be more favorable."
Continued follow-up in this and other studies are needed to show how drug-eluting stents stack up to surgery long term, he added.
"What I think is going to be most interesting is when we extend our survival curves out to five to 7.5 years, and maybe those curves start to separate," Dr. Wilson said. "Right now all we can say is they are close enough to each other that we can't make any predictions."
"This is the type of study that will be very helpful," commented Sidney Smith, M.D., of the University of South Florida in Tampa and a past president of the American Heart Association, who was not involved in the study.
In a single-center observational study, drug-eluting stents and CABG had similar 30-day and three-year outcomes for coronary patients, said James M. Wilson, M.D., of the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston, and colleagues.
The study, presented at the American Heart Association's Conference on Arteriosclerosis, Thrombosis, and Vascular Biology here, represented one of the first reports on outcomes of drug-eluting stents versus bypass grafting.
In previous studies, bare-metal stents had better outcomes at one year that then eroded to equivalence at three years and disadvantage compared with CABG at long-term follow-up, Dr. Wilson said.
"It's a little worrisome that we don't have that early advantage we had with the bare-metal stents," he said. "This surprised us."
Dr. Wilson and colleagues looked at in-hospital and three-year follow-up data from 1,598 unselected coronary-artery patients who underwent isolated primary revascularization by drug-eluting stents or CABG.
Patients were case matched by procedure propensity score to ensure similar patient characteristics between groups. For both, the average age was 64, about 7% had an urgent procedure, about 30% had diabetes, and about 75% had more than one diseased vessel.
Early, 30-day major adverse cardiac and cerebrovascular event findings were:
Similar overall (3.78% CABG versus 5.01% DES, P=NS).
Not significantly different for myocardial infarction between groups (1.67% versus 2.22%, P=NS).
Significantly lower stroke rate with drug eluting stents (1.11% versus 0.11%, P<0.01).
Similar for 30-day mortality (1.67% versus 2.22%, P=NS).
Identical target vessel and target lesion revascularization rates by CABG (0.11% versus 0.11%, P=NS).
Significantly different target vessel and target lesion revascularization rates by drug eluting stents between groups (0.00% versus 1.78%, P<0.01).
For mid-term outcomes, the researchers looked at mortality at three years post-revascularization. They found no statistically significant difference between CABG and drug eluting stents (6.6% versus 9.0%, P=NS).
While drug-eluting stents were expected to offer advantages over bare-metal stents, overconfidence in patient selection appears to have erased any advantage, Dr. Wilson concluded.
"With drug-eluting stents, the data from randomized trials was so exciting I think we began to treat the more difficult lesions with hopes of long-term success," he said.
An FDA advisory panel concluded late last year that drug-eluting stents are safe and effective when used as indicated in stable patients with single-vessel disease. An estimated 60% of the six-million drug-eluting stents implanted worldwide are used off-label in complex lesions and high-risk patients.
"We have a stent that has a reduced likelihood of failure long term but the patients we've chosen to put them in have given away the early advantage," Dr. Wilson said. "If we were to use our patient selection criteria that we used for bare metal stents our outcomes might be more favorable."
Continued follow-up in this and other studies are needed to show how drug-eluting stents stack up to surgery long term, he added.
"What I think is going to be most interesting is when we extend our survival curves out to five to 7.5 years, and maybe those curves start to separate," Dr. Wilson said. "Right now all we can say is they are close enough to each other that we can't make any predictions."
"This is the type of study that will be very helpful," commented Sidney Smith, M.D., of the University of South Florida in Tampa and a past president of the American Heart Association, who was not involved in the study.
Above-Optimal CVD Risk Factors Measured Early in Life Predictive of Future Disease
Above-normal levels of modifiable risk factors for cardiovascular disease for young adults between the ages of 18 and 30 years significantly increases the risk for later developing coronary calcification. The early levels of risk factors were equally or more informative than concurrent risk factor levels, average 15-year levels, or changes in risk factor levels during 15 years, investigators report.
"Thus, early adult levels of modifiable cardiovascular risk factors, albeit relatively low, may be more informative than generally recognized by young adults and their clinicians," writes Catherine Loria, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and colleagues in the April 17 online issue of the Journal of the American College of Cardiology. "Young adults with above-optimal risk factor levels at baseline, who were 2 or 3 times more likely to have coronary artery calcium (CAC), and those with a family history of cardiovascular disease, which predicted CAC independently of established risk factors in the CARDIA [Coronary Artery Risk Development in Young Adults] study, could be targeted for preventive efforts."
In an interview with heartwire, Dr. Loria said that while young adults often have their weight and height recorded, fewer are screened for high blood pressure or abnormal lipid levels.
"Even young adults don't visit their physician as frequently as older adults do," said Dr. Loria. "We're trying to urge young adults and physicians to pay more attention because, while their risk factor levels are generally low, and they might think we don't need to measure these risk factors because they feel they're not at risk, we probably do."
Results From the CARDIA Study
The CARDIA study initially measured risk factor levels in 1985 in 5115 African American and white adults aged 18 to 30 years. These subjects were then followed up for 15 years, and because the study involved young adults, investigators were able to examine the development of cardiovascular disease, as well as the development of risk factors for cardiovascular disease.
Of the more than 3000 participants who were scanned at year 15, when the participants were aged between 33 and 45 years, 9.6% had coronary calcification as assessed by 2 computed tomography (CT) scans. The presence of coronary artery calcium was defined as having a positive non-zero Agatston score using the average of the 2 scans.
For those with blood glucose greater than 110 mg/dL at baseline, there was a 3-fold risk in developing coronary calcium, a 2-fold risk for those with low-density lipoprotein (LDL) cholesterol greater than 130 mg/dL at baseline, and 1.5-fold risk for those with systolic blood pressures above 120/80 mm Hg at baseline. Multivariate-adjusted odds ratios of having coronary artery calcium by ages 33 to 45 years were 1.5 per 10 cigarettes smoked, 1.5 per 30 mg/dL of LDL cholesterol, 1.3 per 10-mmHg systolic blood pressure, and 1.2 per 15 mg/dL glucose, all measured at baseline.
"Thus, early adult levels of modifiable cardiovascular risk factors, albeit relatively low, may be more informative than generally recognized by young adults and their clinicians," writes Catherine Loria, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and colleagues in the April 17 online issue of the Journal of the American College of Cardiology. "Young adults with above-optimal risk factor levels at baseline, who were 2 or 3 times more likely to have coronary artery calcium (CAC), and those with a family history of cardiovascular disease, which predicted CAC independently of established risk factors in the CARDIA [Coronary Artery Risk Development in Young Adults] study, could be targeted for preventive efforts."
In an interview with heartwire, Dr. Loria said that while young adults often have their weight and height recorded, fewer are screened for high blood pressure or abnormal lipid levels.
"Even young adults don't visit their physician as frequently as older adults do," said Dr. Loria. "We're trying to urge young adults and physicians to pay more attention because, while their risk factor levels are generally low, and they might think we don't need to measure these risk factors because they feel they're not at risk, we probably do."
Results From the CARDIA Study
The CARDIA study initially measured risk factor levels in 1985 in 5115 African American and white adults aged 18 to 30 years. These subjects were then followed up for 15 years, and because the study involved young adults, investigators were able to examine the development of cardiovascular disease, as well as the development of risk factors for cardiovascular disease.
Of the more than 3000 participants who were scanned at year 15, when the participants were aged between 33 and 45 years, 9.6% had coronary calcification as assessed by 2 computed tomography (CT) scans. The presence of coronary artery calcium was defined as having a positive non-zero Agatston score using the average of the 2 scans.
For those with blood glucose greater than 110 mg/dL at baseline, there was a 3-fold risk in developing coronary calcium, a 2-fold risk for those with low-density lipoprotein (LDL) cholesterol greater than 130 mg/dL at baseline, and 1.5-fold risk for those with systolic blood pressures above 120/80 mm Hg at baseline. Multivariate-adjusted odds ratios of having coronary artery calcium by ages 33 to 45 years were 1.5 per 10 cigarettes smoked, 1.5 per 30 mg/dL of LDL cholesterol, 1.3 per 10-mmHg systolic blood pressure, and 1.2 per 15 mg/dL glucose, all measured at baseline.
New Strategies for Pulmonary Arterial Hypertension: Evaluation and Management
The availability of newer drugs for pulmonary arterial hypertension (PAH) has radically changed its management and significantly improved both quality of life and mortality for patients, according to a review published in the April issue of the Southern Medical Journal. This review highlights the presentation of PAH, the diagnostic approach, and treatment options.
"Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary vascular circuit, is defined as an elevation in pulmonary arterial pressures and is characterized by symptoms of dyspnea, chest pain, and syncope," write Anne V. LaRaia, MD, and Aaron B. Waxman, MD, PhD, from Massachusetts General Hospital, Harvard Medical School, in Boston, Massachusetts. "If left untreated, the disease carries a high mortality rate, with the most common cause of death being decompensated right-sided heart failure. Over the past 5 years, there have been significant advances in this field in regards to understanding the pathogenesis, diagnosis, and classification of PAH."
PAH is a progressive disease causing narrowing and occlusion of pulmonary blood vessels, and has an estimated median survival of approximately 2.8 years. Despite the development of newer medical therapies, therapeutic options remain limited, and treatment is aimed at improving quality of life and survival.
According to the National Institutes of Health Registry on Primary Pulmonary Hypertension, the definition of PAH is a mean pulmonary arterial pressure of 25 mm Hg or greater at rest, with pulmonary capillary wedge pressure of 15 mm Hg or less, and mean pulmonary arterial pressure greater than 30 mm Hg with exercise.
In 2003, the World Health Organization revised the classification of PAH into 5 categories based in part on etiology: pulmonary arterial hypertension, pulmonary venous hypertension, pulmonary hypertension associated with hypoxemia, pulmonary hypertension resulting from chronic thrombotic or embolic disease, and miscellaneous.
Pulmonary arterial hypertension includes idiopathic PAH; familial PAH; disease associated with collagen vascular disease, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs and toxins, or other diseases (glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); and PAH associated with significant venous or capillary involvement (pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension).
Pulmonary venous hypertension associated with left-sided heart disease includes left-sided atrial or ventricular heart disease and left-sided valvular heart disease.
Pulmonary hypertension associated with hypoxemia includes chronic obstructive pulmonary disease, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation disorders, long-term exposure to high altitude, and developmental abnormalities.
Pulmonary hypertension resulting from chronic thrombotic and/or embolic disease includes thromboembolic obstruction of proximal or distal pulmonary arteries, thromboembolic obstruction of distal pulmonary arteries, and pulmonary embolism caused by tumor, parasites, or foreign material.
The miscellaneous group of PAH includes sarcoidosis, histiocytosis X, lymphangiomatosis, and compression of pulmonary vessels by adenopathy, tumor, or fibrosing mediastinitis.
Whatever the cause, the common end result of processes leading to PAH is elevation of pulmonary artery pressures and vascular resistance, with resultant right-sided heart failure. Progressive dyspnea is almost a cardinal feature of PAH, sometimes accompanied by fatigue, syncope, or chest pain.
Diagnostic workup for PAH includes history focusing on the above features and physical examination findings of paradoxical splitting of the second heart sound, the murmur of pulmonic regurgitation and tricuspid regurgitation, right ventricle heave, increased jugular venous pressure with prominent V waves, hepatomegaly with pulsations of the liver, and lower extremity edema associated with right-sided heart failure.
Electrocardiographic changes may include right ventricular hypertrophy, right atrial enlargement, and right axis deviation. Pulmonary function testing, chest radiography including contrast computed tomography and ventilation perfusion scanning, and transthoracic echocardiography also may be helpful. The gold standard is right-sided heart catheterization.
Current wisdom concerning the endothelial dysfunction underlying PAH includes a decrease in nitric oxide and prostacyclin synthesis, and an increase in thromboxane and enthothelin-1 synthesis, resulting in the typical pathology of small vessel smooth muscle hypertrophy, adventitial and intimal proliferation, and plexiform vascular lesions resulting in vascular thrombosis. This physiological basis provides the rationale for many of the new treatment options.
"The availability of newer drugs has resulted in a radical change in the management of this disease with significant improvement in both quality of life and mortality," the authors write. "Ongoing research promises to lead to a more comprehensive understanding of the genetics, etiology, and pathogenesis of pulmonary arterial hypertension, which may ultimately translate into more effective therapeutic options."
"Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary vascular circuit, is defined as an elevation in pulmonary arterial pressures and is characterized by symptoms of dyspnea, chest pain, and syncope," write Anne V. LaRaia, MD, and Aaron B. Waxman, MD, PhD, from Massachusetts General Hospital, Harvard Medical School, in Boston, Massachusetts. "If left untreated, the disease carries a high mortality rate, with the most common cause of death being decompensated right-sided heart failure. Over the past 5 years, there have been significant advances in this field in regards to understanding the pathogenesis, diagnosis, and classification of PAH."
PAH is a progressive disease causing narrowing and occlusion of pulmonary blood vessels, and has an estimated median survival of approximately 2.8 years. Despite the development of newer medical therapies, therapeutic options remain limited, and treatment is aimed at improving quality of life and survival.
According to the National Institutes of Health Registry on Primary Pulmonary Hypertension, the definition of PAH is a mean pulmonary arterial pressure of 25 mm Hg or greater at rest, with pulmonary capillary wedge pressure of 15 mm Hg or less, and mean pulmonary arterial pressure greater than 30 mm Hg with exercise.
In 2003, the World Health Organization revised the classification of PAH into 5 categories based in part on etiology: pulmonary arterial hypertension, pulmonary venous hypertension, pulmonary hypertension associated with hypoxemia, pulmonary hypertension resulting from chronic thrombotic or embolic disease, and miscellaneous.
Pulmonary arterial hypertension includes idiopathic PAH; familial PAH; disease associated with collagen vascular disease, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs and toxins, or other diseases (glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); and PAH associated with significant venous or capillary involvement (pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension).
Pulmonary venous hypertension associated with left-sided heart disease includes left-sided atrial or ventricular heart disease and left-sided valvular heart disease.
Pulmonary hypertension associated with hypoxemia includes chronic obstructive pulmonary disease, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation disorders, long-term exposure to high altitude, and developmental abnormalities.
Pulmonary hypertension resulting from chronic thrombotic and/or embolic disease includes thromboembolic obstruction of proximal or distal pulmonary arteries, thromboembolic obstruction of distal pulmonary arteries, and pulmonary embolism caused by tumor, parasites, or foreign material.
The miscellaneous group of PAH includes sarcoidosis, histiocytosis X, lymphangiomatosis, and compression of pulmonary vessels by adenopathy, tumor, or fibrosing mediastinitis.
Whatever the cause, the common end result of processes leading to PAH is elevation of pulmonary artery pressures and vascular resistance, with resultant right-sided heart failure. Progressive dyspnea is almost a cardinal feature of PAH, sometimes accompanied by fatigue, syncope, or chest pain.
Diagnostic workup for PAH includes history focusing on the above features and physical examination findings of paradoxical splitting of the second heart sound, the murmur of pulmonic regurgitation and tricuspid regurgitation, right ventricle heave, increased jugular venous pressure with prominent V waves, hepatomegaly with pulsations of the liver, and lower extremity edema associated with right-sided heart failure.
Electrocardiographic changes may include right ventricular hypertrophy, right atrial enlargement, and right axis deviation. Pulmonary function testing, chest radiography including contrast computed tomography and ventilation perfusion scanning, and transthoracic echocardiography also may be helpful. The gold standard is right-sided heart catheterization.
Current wisdom concerning the endothelial dysfunction underlying PAH includes a decrease in nitric oxide and prostacyclin synthesis, and an increase in thromboxane and enthothelin-1 synthesis, resulting in the typical pathology of small vessel smooth muscle hypertrophy, adventitial and intimal proliferation, and plexiform vascular lesions resulting in vascular thrombosis. This physiological basis provides the rationale for many of the new treatment options.
"The availability of newer drugs has resulted in a radical change in the management of this disease with significant improvement in both quality of life and mortality," the authors write. "Ongoing research promises to lead to a more comprehensive understanding of the genetics, etiology, and pathogenesis of pulmonary arterial hypertension, which may ultimately translate into more effective therapeutic options."
Understanding Empathy: Can You Feel My Pain?
Richard A. Friedman
“Can I ask you a question?” the young woman ventured. “Have you ever been depressed? Do you have any idea how bad it feels?”
The patient, a married woman in her late 20s, had been tearfully describing her symptoms of depression during a consultation when she suddenly popped this question.
How could I possibly understand or help her, she seemed to be asking, if I had not personally experienced her pain?
Her question caught me by surprise and made me pause. O.K., I’ll admit it. I’m a cheerful guy who’s never really tasted clinical depression. But along the way I think I’ve successfully treated many severely depressed patients.
Is shared experience really necessary for a physician to understand or treat a patient? I wonder. After all, who would argue that a cardiologist would be more competent if he had had his own heart attack, or an oncologist more effective if he had had a brush with cancer?
Of course, a patient might feel more comfortable with a physician who has had personal experience with his medical illness, but that alone wouldn’t guarantee understanding, much less good treatment.
Still, many patients want their doctor to be someone with whom they can identify, not just a technically competent professional who can alleviate their pain.
As a psychiatrist, I’ve met many patients who have made requests for a specific type of therapist: African-Americans who want a black psychiatrist, Orthodox Jews who insist on a Jewish psychotherapist, women who ask for a feminist therapist and so on.
Not long ago, a gay man in his 30s called me to ask for a referral to a gay therapist. He was adamant about seeing only a gay clinician. “I can’t take the chance of getting a homophobic shrink,” he said.
His assumption was that if a therapist shared his sexual orientation or ethnic group, there would be a kind of guaranteed basis for understanding or acceptance.
I did, in fact, refer him to an excellent colleague who happens to be gay, but the brief conversation left me troubled. All these patients who were searching for understanding had a misconception, I think, of what empathy is all about.
What is critical to understanding someone is not necessarily having had his or her experience; it is being able to imagine what it would be like to have it. Thus, I do not have to be black to empathize with the toxic effects of racial prejudice, or be a woman to know how I would feel about being denied promotion on the basis of sex.
Contrary to what many people believe, being empathic is not the same thing as being nice. In fact, empathy can sometimes be put to a very dark purpose.
When the Nazis were bombing Rotterdam in World War II, for example, they put sirens on the Stuka dive-bombers knowing full well that the sound would terrify and disorganize the Dutch. The Nazis imagined perfectly how the Dutch would feel and react. Fiendish, but the very essence of empathy.
In the right hands, empathy has tremendous positive therapeutic force and can narrow what looks like an unbridgeable gap between patients and therapists.
A few years back, I saw an elderly woman who had just lost her husband to cancer. “Oh, I hadn’t realized you were so young!” she exclaimed. “No offense, but maybe I need to see someone who’s a bit older.”
I asked her, “Are you worried that I can’t know what it feels like to lose someone you love and face life without him?”
True, I had never lost a partner, but it wasn’t hard to imagine her grief and anxiety about her future. That must have done the trick, because she stayed in treatment and never again mentioned my age.
Sometimes, though, patients should get exactly what they ask for in a therapist. One of my residents once saw a young woman from Africa who had survived hideous torture and rape and said that she didn’t think she could see a male therapist.
That struck me as entirely appropriate. Given her trauma, she simply could not have put her trust in a male therapist, no matter how empathic he might actually be.
What about patients whose demand for a particular therapist springs from nothing more than everyday prejudice? I remember a patient who once stormed into my office and demanded a white therapist to replace his therapist, who was black.
That’s a request I turned down, even knowing that this patient’s biased beliefs were an appropriate target for treatment. To do otherwise would have vindicated his prejudice and fundamentally compromised the therapy from the start.
In the end, empathy is what makes it possible for us to read each other. And it is the reason your doctor can understand your problem without actually having to live it.
Richard A. Friedman is director of the psychopharmacology clinic at the Weill Medical College of Cornell University.
“Can I ask you a question?” the young woman ventured. “Have you ever been depressed? Do you have any idea how bad it feels?”
The patient, a married woman in her late 20s, had been tearfully describing her symptoms of depression during a consultation when she suddenly popped this question.
How could I possibly understand or help her, she seemed to be asking, if I had not personally experienced her pain?
Her question caught me by surprise and made me pause. O.K., I’ll admit it. I’m a cheerful guy who’s never really tasted clinical depression. But along the way I think I’ve successfully treated many severely depressed patients.
Is shared experience really necessary for a physician to understand or treat a patient? I wonder. After all, who would argue that a cardiologist would be more competent if he had had his own heart attack, or an oncologist more effective if he had had a brush with cancer?
Of course, a patient might feel more comfortable with a physician who has had personal experience with his medical illness, but that alone wouldn’t guarantee understanding, much less good treatment.
Still, many patients want their doctor to be someone with whom they can identify, not just a technically competent professional who can alleviate their pain.
As a psychiatrist, I’ve met many patients who have made requests for a specific type of therapist: African-Americans who want a black psychiatrist, Orthodox Jews who insist on a Jewish psychotherapist, women who ask for a feminist therapist and so on.
Not long ago, a gay man in his 30s called me to ask for a referral to a gay therapist. He was adamant about seeing only a gay clinician. “I can’t take the chance of getting a homophobic shrink,” he said.
His assumption was that if a therapist shared his sexual orientation or ethnic group, there would be a kind of guaranteed basis for understanding or acceptance.
I did, in fact, refer him to an excellent colleague who happens to be gay, but the brief conversation left me troubled. All these patients who were searching for understanding had a misconception, I think, of what empathy is all about.
What is critical to understanding someone is not necessarily having had his or her experience; it is being able to imagine what it would be like to have it. Thus, I do not have to be black to empathize with the toxic effects of racial prejudice, or be a woman to know how I would feel about being denied promotion on the basis of sex.
Contrary to what many people believe, being empathic is not the same thing as being nice. In fact, empathy can sometimes be put to a very dark purpose.
When the Nazis were bombing Rotterdam in World War II, for example, they put sirens on the Stuka dive-bombers knowing full well that the sound would terrify and disorganize the Dutch. The Nazis imagined perfectly how the Dutch would feel and react. Fiendish, but the very essence of empathy.
In the right hands, empathy has tremendous positive therapeutic force and can narrow what looks like an unbridgeable gap between patients and therapists.
A few years back, I saw an elderly woman who had just lost her husband to cancer. “Oh, I hadn’t realized you were so young!” she exclaimed. “No offense, but maybe I need to see someone who’s a bit older.”
I asked her, “Are you worried that I can’t know what it feels like to lose someone you love and face life without him?”
True, I had never lost a partner, but it wasn’t hard to imagine her grief and anxiety about her future. That must have done the trick, because she stayed in treatment and never again mentioned my age.
Sometimes, though, patients should get exactly what they ask for in a therapist. One of my residents once saw a young woman from Africa who had survived hideous torture and rape and said that she didn’t think she could see a male therapist.
That struck me as entirely appropriate. Given her trauma, she simply could not have put her trust in a male therapist, no matter how empathic he might actually be.
What about patients whose demand for a particular therapist springs from nothing more than everyday prejudice? I remember a patient who once stormed into my office and demanded a white therapist to replace his therapist, who was black.
That’s a request I turned down, even knowing that this patient’s biased beliefs were an appropriate target for treatment. To do otherwise would have vindicated his prejudice and fundamentally compromised the therapy from the start.
In the end, empathy is what makes it possible for us to read each other. And it is the reason your doctor can understand your problem without actually having to live it.
Richard A. Friedman is director of the psychopharmacology clinic at the Weill Medical College of Cornell University.
Medicine and the Drug Industry, a Morality Tale
Abigail Zuger
It was in 1949 that Elvin Stakman, president of the American Association for the Advancement of Science, issued the membership their marching orders: “Science cannot stop while ethics catches up.”
And sure enough, from bombs to clones, the ethicists have generally kept to the rear of the scientific parade: they are the ones with the big brooms trying to restore order after the floats and the elephants go by.
Those brooms sweep slowly. Often, by the time the ethicists finish laying out facts and weighing relevant moral values, the worst of any given crisis has passed. But recently, those who work in medicine have moved closer to the fray: they staff acute-care hospitals and monitor events in real time, aiming for a little less retrospective philosophy and a little more damage control.
In this proactive spirit Howard Brody, a medical ethicist, has brought his discipline’s tools to the relationship between the medical profession and the pharmaceutical industry. This problematic tangle of moral compromise (or triumphant health-promoting collaboration, depending on your point of view) has inspired several polemics by physicians in recent years, all of them straightforward indictments of the pharmaceutical industry and its for-profit webs.
Dr. Brody is also a physician, but he aims for the measured cadences of the ethicist instead, calmly laying out the relevant facts and then reasoning from basic principles to determine whether the medicine-pharmaceutical relationship, as it stands now, is an ethical one or not.
That Dr. Brody manages to deliver a hundred-odd pages of determinedly objective analysis before he, too, lets the righteous indignation roll should not really be called a failure of methodology: even as he carefully lays out the facts in this impressively comprehensive book, those facts begin to speak damningly for themselves.
The small-time operations that grew up into modern medicine and Big Pharma joined together back in the late 19th century, allied in the name of scientific medicine against a variety of dubious health-care entrepreneurs. The A.M.A. actually called the early pharmaceutical companies the “ethical” drug makers, to distinguish them from unscrupulous patent-medicine peddlers.
Over time, this casual alliance has been reinforced with such complex and often invisible bonds that, in Dr. Brody’s title metaphor, medicine and pharma are now “hooked” like two pieces of Velcro, tethered by a million barbs and as dependent on each other as any addicts are on their substance of choice.
Dr. Brody systematically analyzes the levels of connection, from the lowly drug salesman buying lunch for a roomful of medical students (future customers all) to the lucrative contracts and patents that simultaneously fuel medical research, fill corporate coffers and give us, as the industry doggedly and quite correctly points out, dozens of truly miraculous life-saving drugs.
Many of these interactions are probably now familiar to most readers: the omnipresent logo-bearing trinkets festooning medical offices, the free samples of the latest, most expensive drugs, the “ask your doctor” television ads.
Less familiar may be some of industry’s other friendly overtures: the lavish junkets and cash rewards for some “high-prescribing” doctors; the subtle manipulations of research data; the way-too-generous financing of postgraduate medical education; the very cozy relationship with the Food and Drug Administration and its physician consultants; and a casually Orwellian interference with the average physician’s prescription pad.
A drug salesman recalls for Dr. Brody the time his company asked a local doctor to evaluate various sales presentations for a particular drug: “He’d been selected because our data showed that he was a relatively low prescriber. ...Basically, the company was willing to bet $500 or $750 that if he heard the same drug pitch all day, by the end of the day he’d be so brainwashed that he could not possibly prescribe any other drug but ours.”
All this mutual back-scratching would be fine if patients’ interests were indeed being served. But ample data indicates quite the reverse. Patients, after all, are the ones who pay for expensive drugs when cheaper would do as well, and the ones who swallow dangerous drugs nudged to market by their manufacturers.
Many individual problematic drugs make an appearance here. Chloromycetin, a toxic antibiotic from the 1950s, was relentlessly promoted by its manufacturer for routine use until the day its patent expired. (Still available in generic form, it is now used only as a last resort.) Thalidomide never caused an epidemic of birth defects in this country, as it did in Germany, only because a single stubborn F.D.A. officer was dissatisfied with the drug’s safety profile, despite the manufacturer’s repeated assurances that everything was fine.
The epitaph of the recently withdrawn painkiller Vioxx, whose virtues were subtly spun to the medical community in prestigious research journals, is still being written in litigation around the country.
“Research that is driven by marketing rather than by scientific aims would seem, in the end, to be low-quality research,” Dr. Brody comments mildly about the Vioxx fiasco.
His overall conclusion is similarly low-key: “A profession is not just a way of making money; it’s a form of public trust. ...Medicine has for many decades now been betraying this public trust.”
It is not a particularly surprising conclusion, and, in fact, there is relatively little in this book to surprise anyone familiar with the territory. Rather than new material, it provides a meticulously referenced compendium of all the relevant history and commentary (including, for full disclosure, excerpts from one of this reviewer’s columns in this newspaper).
Its breadth translates into a lack of depth in some areas, especially the final section, in which Dr. Brody tries to outline a feasible solution to the mess. His suggestions are cogent but a little skimpy, given that absent an act of God, it will probably take an act of Congress to pry medicine and industry apart someday, preferably as part of thoroughgoing health care reform.
Still, for a detailed overview of this very jagged terrain, if not for a map of the pathway out, a better general guide than this one is hard to imagine.
It was in 1949 that Elvin Stakman, president of the American Association for the Advancement of Science, issued the membership their marching orders: “Science cannot stop while ethics catches up.”
And sure enough, from bombs to clones, the ethicists have generally kept to the rear of the scientific parade: they are the ones with the big brooms trying to restore order after the floats and the elephants go by.
Those brooms sweep slowly. Often, by the time the ethicists finish laying out facts and weighing relevant moral values, the worst of any given crisis has passed. But recently, those who work in medicine have moved closer to the fray: they staff acute-care hospitals and monitor events in real time, aiming for a little less retrospective philosophy and a little more damage control.
In this proactive spirit Howard Brody, a medical ethicist, has brought his discipline’s tools to the relationship between the medical profession and the pharmaceutical industry. This problematic tangle of moral compromise (or triumphant health-promoting collaboration, depending on your point of view) has inspired several polemics by physicians in recent years, all of them straightforward indictments of the pharmaceutical industry and its for-profit webs.
Dr. Brody is also a physician, but he aims for the measured cadences of the ethicist instead, calmly laying out the relevant facts and then reasoning from basic principles to determine whether the medicine-pharmaceutical relationship, as it stands now, is an ethical one or not.
That Dr. Brody manages to deliver a hundred-odd pages of determinedly objective analysis before he, too, lets the righteous indignation roll should not really be called a failure of methodology: even as he carefully lays out the facts in this impressively comprehensive book, those facts begin to speak damningly for themselves.
The small-time operations that grew up into modern medicine and Big Pharma joined together back in the late 19th century, allied in the name of scientific medicine against a variety of dubious health-care entrepreneurs. The A.M.A. actually called the early pharmaceutical companies the “ethical” drug makers, to distinguish them from unscrupulous patent-medicine peddlers.
Over time, this casual alliance has been reinforced with such complex and often invisible bonds that, in Dr. Brody’s title metaphor, medicine and pharma are now “hooked” like two pieces of Velcro, tethered by a million barbs and as dependent on each other as any addicts are on their substance of choice.
Dr. Brody systematically analyzes the levels of connection, from the lowly drug salesman buying lunch for a roomful of medical students (future customers all) to the lucrative contracts and patents that simultaneously fuel medical research, fill corporate coffers and give us, as the industry doggedly and quite correctly points out, dozens of truly miraculous life-saving drugs.
Many of these interactions are probably now familiar to most readers: the omnipresent logo-bearing trinkets festooning medical offices, the free samples of the latest, most expensive drugs, the “ask your doctor” television ads.
Less familiar may be some of industry’s other friendly overtures: the lavish junkets and cash rewards for some “high-prescribing” doctors; the subtle manipulations of research data; the way-too-generous financing of postgraduate medical education; the very cozy relationship with the Food and Drug Administration and its physician consultants; and a casually Orwellian interference with the average physician’s prescription pad.
A drug salesman recalls for Dr. Brody the time his company asked a local doctor to evaluate various sales presentations for a particular drug: “He’d been selected because our data showed that he was a relatively low prescriber. ...Basically, the company was willing to bet $500 or $750 that if he heard the same drug pitch all day, by the end of the day he’d be so brainwashed that he could not possibly prescribe any other drug but ours.”
All this mutual back-scratching would be fine if patients’ interests were indeed being served. But ample data indicates quite the reverse. Patients, after all, are the ones who pay for expensive drugs when cheaper would do as well, and the ones who swallow dangerous drugs nudged to market by their manufacturers.
Many individual problematic drugs make an appearance here. Chloromycetin, a toxic antibiotic from the 1950s, was relentlessly promoted by its manufacturer for routine use until the day its patent expired. (Still available in generic form, it is now used only as a last resort.) Thalidomide never caused an epidemic of birth defects in this country, as it did in Germany, only because a single stubborn F.D.A. officer was dissatisfied with the drug’s safety profile, despite the manufacturer’s repeated assurances that everything was fine.
The epitaph of the recently withdrawn painkiller Vioxx, whose virtues were subtly spun to the medical community in prestigious research journals, is still being written in litigation around the country.
“Research that is driven by marketing rather than by scientific aims would seem, in the end, to be low-quality research,” Dr. Brody comments mildly about the Vioxx fiasco.
His overall conclusion is similarly low-key: “A profession is not just a way of making money; it’s a form of public trust. ...Medicine has for many decades now been betraying this public trust.”
It is not a particularly surprising conclusion, and, in fact, there is relatively little in this book to surprise anyone familiar with the territory. Rather than new material, it provides a meticulously referenced compendium of all the relevant history and commentary (including, for full disclosure, excerpts from one of this reviewer’s columns in this newspaper).
Its breadth translates into a lack of depth in some areas, especially the final section, in which Dr. Brody tries to outline a feasible solution to the mess. His suggestions are cogent but a little skimpy, given that absent an act of God, it will probably take an act of Congress to pry medicine and industry apart someday, preferably as part of thoroughgoing health care reform.
Still, for a detailed overview of this very jagged terrain, if not for a map of the pathway out, a better general guide than this one is hard to imagine.
Migraine may protect against cognitive decline
Women with a lifetime history of migraine have less cognitive decline over time than women without migraine. It's possible, researchers suggest, that antimigraine medications, as well as diet and behavior changes, play a role in the apparent protective effect of migraine on cognition.
Dr. Amanda Kalaydjian of Johns Hopkins Bloomberg School of Public Health, Baltimore and colleagues examined the relationship between migraine headaches and cognitive functioning in 1,448 women participating in the Baltimore Epidemiologic Catchment Area Study.
They compared scores on immediate and delayed recall tests and on the Mini-Mental State Examination (MMSE) administered between 1993 and 1996 and again in 2004 and 2005. A total of 204 migraineurs and 1,244 nonmigraineurs participated.
According to the team's report in the current issue of Neurology, migraineurs scored lower on tests of immediate and delayed memory at the beginning of the study, but their performance declined significantly less over time compared with that of the nonmigraineurs.
These associations were observed specifically in migraineurs with aura who, over 12 years, had a 26-percent and 47-percent lower word decline on the immediate and delayed recall tests, respectively, the authors report.
The effects of migraine with aura on the MMSE were restricted to individuals older than age 50. Among those younger than 50 years, migraineurs with aura declined at the same rate as those without migraine.
In a statement issued by the American Academy of Neurology, Kalaydjian said: "Some medications for migraine headaches, such as ibuprofen, which may have a protective effect on memory, may be partially responsible for our findings, but it's unlikely to explain this association given we adjusted for this possibility in our study and the medications showed no indication of a significant protective effect."
Another factor that needs to be explored is the possibility that migraineurs may alte
Dr. Amanda Kalaydjian of Johns Hopkins Bloomberg School of Public Health, Baltimore and colleagues examined the relationship between migraine headaches and cognitive functioning in 1,448 women participating in the Baltimore Epidemiologic Catchment Area Study.
They compared scores on immediate and delayed recall tests and on the Mini-Mental State Examination (MMSE) administered between 1993 and 1996 and again in 2004 and 2005. A total of 204 migraineurs and 1,244 nonmigraineurs participated.
According to the team's report in the current issue of Neurology, migraineurs scored lower on tests of immediate and delayed memory at the beginning of the study, but their performance declined significantly less over time compared with that of the nonmigraineurs.
These associations were observed specifically in migraineurs with aura who, over 12 years, had a 26-percent and 47-percent lower word decline on the immediate and delayed recall tests, respectively, the authors report.
The effects of migraine with aura on the MMSE were restricted to individuals older than age 50. Among those younger than 50 years, migraineurs with aura declined at the same rate as those without migraine.
In a statement issued by the American Academy of Neurology, Kalaydjian said: "Some medications for migraine headaches, such as ibuprofen, which may have a protective effect on memory, may be partially responsible for our findings, but it's unlikely to explain this association given we adjusted for this possibility in our study and the medications showed no indication of a significant protective effect."
Another factor that needs to be explored is the possibility that migraineurs may alte
UCLA study finds prostate cancer treatments impact on quality of life
3 most common treatments affect men in different ways
A rigorous, long-term study of quality of life in patients who underwent one of the three most common treatments for prostate cancer found that each affected men's lives in different ways. The findings provide invaluable information for men with prostate cancer who are facing vital treatment decisions.
Researchers studied quality of life in men who either underwent radical prostatectomy, implantation of radioactive seeds in their prostate gland or had external beam radiation therapy. The three treatment options rank about equally in survival outcomes for most men, so specific impacts on quality of life become paramount in making treatment decisions, said Dr. Mark Litwin, the study's lead author and a researcher at UCLA's Jonsson Cancer Center.
"The good news is that overall mental and physical well-being were not profoundly affected by any of the three treatment choices," Litwin said. "That's good news for men with the sword of prostate cancer hanging over their heads. In general, they'll be OK no matter which of the three options they choose."
However, each of the three options did negatively affect quality of life, at least temporarily, with problems ranging from erectile dysfunction and minor incontinence to urinary and bowel irritation.
The study tracked 580 men for five years. The study results, published in the June 1, 2007 issue of the peer-reviewed journal CANCER, represent data from the first two years of the study. Those years, Litwin said, are when most of the negative impacts surface and resolve.
Seed implantation, also known as brachytherapy, has been touted in marketing campaigns as the best of the three options with the shortest recovery time and the fewest sexual dysfunction side effects, Litwin said.
"These campaigns say 'Get your seed implants on Monday, play golf on Tuesday' and that's just not true," said Litwin, a professor of urology and health services. "Men need to have the most accurate information when making vital decisions about what type to treatment they'll get.. They need facts, not hype."
A rigorous, long-term study of quality of life in patients who underwent one of the three most common treatments for prostate cancer found that each affected men's lives in different ways. The findings provide invaluable information for men with prostate cancer who are facing vital treatment decisions.
Researchers studied quality of life in men who either underwent radical prostatectomy, implantation of radioactive seeds in their prostate gland or had external beam radiation therapy. The three treatment options rank about equally in survival outcomes for most men, so specific impacts on quality of life become paramount in making treatment decisions, said Dr. Mark Litwin, the study's lead author and a researcher at UCLA's Jonsson Cancer Center.
"The good news is that overall mental and physical well-being were not profoundly affected by any of the three treatment choices," Litwin said. "That's good news for men with the sword of prostate cancer hanging over their heads. In general, they'll be OK no matter which of the three options they choose."
However, each of the three options did negatively affect quality of life, at least temporarily, with problems ranging from erectile dysfunction and minor incontinence to urinary and bowel irritation.
The study tracked 580 men for five years. The study results, published in the June 1, 2007 issue of the peer-reviewed journal CANCER, represent data from the first two years of the study. Those years, Litwin said, are when most of the negative impacts surface and resolve.
Seed implantation, also known as brachytherapy, has been touted in marketing campaigns as the best of the three options with the shortest recovery time and the fewest sexual dysfunction side effects, Litwin said.
"These campaigns say 'Get your seed implants on Monday, play golf on Tuesday' and that's just not true," said Litwin, a professor of urology and health services. "Men need to have the most accurate information when making vital decisions about what type to treatment they'll get.. They need facts, not hype."
Antioxidant found in many foods and red wine is potent and selective killer of leukemia cells
University of Pittsburgh researchers show compound kills leukemia cells while sparing normal, healthy cells
PITTSBURGH, April 23 -- A naturally occurring compound found in many fruits and vegetables as well as red wine, selectively kills leukemia cells in culture while showing no discernible toxicity against healthy cells, according to a study by researchers at the University of Pittsburgh School of Medicine. These findings, which were published online March 20 in the Journal of Biological Chemistry and will be in press on May 4, offer hope for a more selective, less toxic therapy for leukemia.
“Current treatments for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for many years afterward. So, there is an intensive search for more targeted therapies for leukemia worldwide,” said corresponding author Xiao-Ming Yin, M.D., Ph.D., associate professor of pathology, University of Pittsburgh School of Medicine.
Leukemia is not a single disease but a number of related cancers that start in the blood-forming cells of the bone marrow. Meaning literally “white blood” in Greek, leukemia occurs when there is an excess of abnormal white blood cells. There are both acute and chronic forms of leukemia, each with many subtypes that vary in their response to treatment. According to the National Cancer Institute, about 44,000 new leukemia cases will be diagnosed in the United States in 2007, and there will be about 22,000 leukemia-related deaths.
Based on previous reports that anthocyanidins, a group of naturally occurring compounds widely available in fruits and vegetables as well as red wine, have chemopreventive properties, Dr. Yin and his collaborators studied the effects and the mechanisms of the most common type of a naturally modified anthocyanidin, known as cyanidin-3-rutinoside, or C-3-R, which was extracted and purified from black raspberries, in several leukemia and lymphoma cell lines.
They found that C-3-R caused about 50 percent of a human leukemia cell line known as HL-60 to undergo programmed cell death, or apoptosis, within about 18 hours of treatment at low doses. When they more than doubled the concentration of C-3-R, virtually all of the leukemia cells became apoptotic and died. C-3-R also induced apoptosis in other human leukemia and lymphoma cell lines.
PITTSBURGH, April 23 -- A naturally occurring compound found in many fruits and vegetables as well as red wine, selectively kills leukemia cells in culture while showing no discernible toxicity against healthy cells, according to a study by researchers at the University of Pittsburgh School of Medicine. These findings, which were published online March 20 in the Journal of Biological Chemistry and will be in press on May 4, offer hope for a more selective, less toxic therapy for leukemia.
“Current treatments for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for many years afterward. So, there is an intensive search for more targeted therapies for leukemia worldwide,” said corresponding author Xiao-Ming Yin, M.D., Ph.D., associate professor of pathology, University of Pittsburgh School of Medicine.
Leukemia is not a single disease but a number of related cancers that start in the blood-forming cells of the bone marrow. Meaning literally “white blood” in Greek, leukemia occurs when there is an excess of abnormal white blood cells. There are both acute and chronic forms of leukemia, each with many subtypes that vary in their response to treatment. According to the National Cancer Institute, about 44,000 new leukemia cases will be diagnosed in the United States in 2007, and there will be about 22,000 leukemia-related deaths.
Based on previous reports that anthocyanidins, a group of naturally occurring compounds widely available in fruits and vegetables as well as red wine, have chemopreventive properties, Dr. Yin and his collaborators studied the effects and the mechanisms of the most common type of a naturally modified anthocyanidin, known as cyanidin-3-rutinoside, or C-3-R, which was extracted and purified from black raspberries, in several leukemia and lymphoma cell lines.
They found that C-3-R caused about 50 percent of a human leukemia cell line known as HL-60 to undergo programmed cell death, or apoptosis, within about 18 hours of treatment at low doses. When they more than doubled the concentration of C-3-R, virtually all of the leukemia cells became apoptotic and died. C-3-R also induced apoptosis in other human leukemia and lymphoma cell lines.
Monday, April 23, 2007
Flu Epidemics Linked to Surge in Coronary Heart Disease Deaths
HOUSTON, April 20 -- A large percentage of influenza deaths are the result of disease-triggered acute myocardial infarctions, researchers here reported on the basis of autopsy-proven data.
In a week during a flu epidemic, the chances of dying of a heart attack increased by 30% and of dying of chronic ischemic heart disease by 10%, reported Mohammad Madjid, M.D., of the University of Texas here, and colleagues, online in the European Heart Journal.
Influenza causes up to an estimated 92,000 U.S. deaths a year as a result of myocardial infarction alone, they reported on the basis of their clinical observations and analyses of published trials.
Many of these deaths could be prevented if every high-risk patient had an annual flu shot. Dr. Madjid and colleagues wrote.
Working with Russian colleagues at the St. Petersburg Medical Academy, the researchers studied the impact of influenza on coronary deaths (acute myocardial infarction and chronic ischemic heart disease) in autopsies conducted from 1993 to 2000 in St. Petersburg.
St. Petersburg was chosen because unlike previous studies that relied on death certificates, a high rate of autopsy-proven fatal cases was available (autopsy rate was almost 70%), the researchers said.
Doctors often neglect to list flu on death certificates if their patient died of a heart attack, and, conversely, heart attack symptoms can be missed in patients with flu and pneumonia, they said.
Furthermore at the time of the study, only a small minority (<3%) of patients in St. Petersburg were receiving flu shots and statin drugs, providing a snapshot of the natural history of these coronary deaths.
In an eight-year review of 34,892 autopsies, there were 11,892 deaths of an acute MI and 23,000 of chronic ischemic heart disease. The median age was 75 for women and 65 for men.
In every year, there was a peak of deaths from MI and chronic ischemic heart disease, and these deaths coincided with an influenza epidemic and winter peaks of acute respiratory disease.
A similar pattern was seen for each subgroup of men and women, for those 50 or older, and for those 70 or older, the researchers said.
When comparing the average influenza epidemic weeks to average off-season weeks, the odds for deaths from MI and from chronic ischemic heart disease increased by 1.30 (95% confidence interval, 1.08-1.56) and 1.10 (CI: 0.97-1.26), respectively, the investigators reported.
Cross-correlation analysis found that coronary mortality echoed acute respiratory disease activity during peak seasonal times and across multiple years, the researchers reported.
Among study limitations, the researchers cited the lack of access to person-specific data on medications and risk factors, or other autopsy diagnoses. Meteorological data to assess impact on influenza and cardiac mortality were lacking and were out of the scope of this study. However, they said, other groups have shown that influenza remains a major determinant of winter's excess mortality.
Influenza and other upper respiratory infections may trigger cardiovascular events by causing an acute and severe inflammatory state in the body, which can lead to destabilization and rupture of atherosclerotic plaques and cause heart attacks, the researchers said.
Recent published reports show that deaths attributed to influenza are increasing in the U.S., and the disease is now the fourth major cause of mortality in the U.S, Dr. Madjid said. Accordingly, he said, it has been noted that during influenza epidemics (except for the 1918 Spanish flu epidemic) roughly twice as many persons die of cardiac causes as from influenza.
Recognition of influenza as a trigger for acute coronary events calls for more intensive efforts to increase the vaccination rate in those at risk for coronary heart disease. This may be especially important in influenza pandemics when a high mortality rate may be expected among the elderly and those with heart disease, the researchers wrote.
Vigorous use of heart-protective medications such as statins during pandemics may also prevent may deaths, they added.
The benefits of influenza vaccination for cardiac patients have been recognized by the American Heart Association and the American College of Cardiology.
In a week during a flu epidemic, the chances of dying of a heart attack increased by 30% and of dying of chronic ischemic heart disease by 10%, reported Mohammad Madjid, M.D., of the University of Texas here, and colleagues, online in the European Heart Journal.
Influenza causes up to an estimated 92,000 U.S. deaths a year as a result of myocardial infarction alone, they reported on the basis of their clinical observations and analyses of published trials.
Many of these deaths could be prevented if every high-risk patient had an annual flu shot. Dr. Madjid and colleagues wrote.
Working with Russian colleagues at the St. Petersburg Medical Academy, the researchers studied the impact of influenza on coronary deaths (acute myocardial infarction and chronic ischemic heart disease) in autopsies conducted from 1993 to 2000 in St. Petersburg.
St. Petersburg was chosen because unlike previous studies that relied on death certificates, a high rate of autopsy-proven fatal cases was available (autopsy rate was almost 70%), the researchers said.
Doctors often neglect to list flu on death certificates if their patient died of a heart attack, and, conversely, heart attack symptoms can be missed in patients with flu and pneumonia, they said.
Furthermore at the time of the study, only a small minority (<3%) of patients in St. Petersburg were receiving flu shots and statin drugs, providing a snapshot of the natural history of these coronary deaths.
In an eight-year review of 34,892 autopsies, there were 11,892 deaths of an acute MI and 23,000 of chronic ischemic heart disease. The median age was 75 for women and 65 for men.
In every year, there was a peak of deaths from MI and chronic ischemic heart disease, and these deaths coincided with an influenza epidemic and winter peaks of acute respiratory disease.
A similar pattern was seen for each subgroup of men and women, for those 50 or older, and for those 70 or older, the researchers said.
When comparing the average influenza epidemic weeks to average off-season weeks, the odds for deaths from MI and from chronic ischemic heart disease increased by 1.30 (95% confidence interval, 1.08-1.56) and 1.10 (CI: 0.97-1.26), respectively, the investigators reported.
Cross-correlation analysis found that coronary mortality echoed acute respiratory disease activity during peak seasonal times and across multiple years, the researchers reported.
Among study limitations, the researchers cited the lack of access to person-specific data on medications and risk factors, or other autopsy diagnoses. Meteorological data to assess impact on influenza and cardiac mortality were lacking and were out of the scope of this study. However, they said, other groups have shown that influenza remains a major determinant of winter's excess mortality.
Influenza and other upper respiratory infections may trigger cardiovascular events by causing an acute and severe inflammatory state in the body, which can lead to destabilization and rupture of atherosclerotic plaques and cause heart attacks, the researchers said.
Recent published reports show that deaths attributed to influenza are increasing in the U.S., and the disease is now the fourth major cause of mortality in the U.S, Dr. Madjid said. Accordingly, he said, it has been noted that during influenza epidemics (except for the 1918 Spanish flu epidemic) roughly twice as many persons die of cardiac causes as from influenza.
Recognition of influenza as a trigger for acute coronary events calls for more intensive efforts to increase the vaccination rate in those at risk for coronary heart disease. This may be especially important in influenza pandemics when a high mortality rate may be expected among the elderly and those with heart disease, the researchers wrote.
Vigorous use of heart-protective medications such as statins during pandemics may also prevent may deaths, they added.
The benefits of influenza vaccination for cardiac patients have been recognized by the American Heart Association and the American College of Cardiology.
Reduced Sodium Intake May Lower Cardiovascular Disease Risk
Reduction in dietary sodium may lower the risk for cardiovascular disease among prehypertensive patients, according to a study published early online in the British Medical Journal.
Researchers evaluated long-term follow-up data on some 2400 prehypertensive adults who had been randomized to reduced sodium intake or usual care in the two Trials of Hypertension Prevention (TOHP). Ten to fifteen years after the trials ended, the risk for cardiovascular disease was significantly lower in the intervention group than in the control group (adjusted relative risk, 0.70). Results of a final follow-up questionnaire suggested that intervention patients had maintained lower sodium intake than controls.
The authors conclude that "sodium reduction, previously shown to lower blood pressure and prevent hypertension, also seems to prevent cardiovascular disease." They add that their findings provide "strong support for population-wide reduction in dietary sodium intake to prevent cardiovascular disease."
Link: BMJ article (Free PDF)
Researchers evaluated long-term follow-up data on some 2400 prehypertensive adults who had been randomized to reduced sodium intake or usual care in the two Trials of Hypertension Prevention (TOHP). Ten to fifteen years after the trials ended, the risk for cardiovascular disease was significantly lower in the intervention group than in the control group (adjusted relative risk, 0.70). Results of a final follow-up questionnaire suggested that intervention patients had maintained lower sodium intake than controls.
The authors conclude that "sodium reduction, previously shown to lower blood pressure and prevent hypertension, also seems to prevent cardiovascular disease." They add that their findings provide "strong support for population-wide reduction in dietary sodium intake to prevent cardiovascular disease."
Link: BMJ article (Free PDF)
Sunday, April 22, 2007
Missed Signals
1. Symptoms
The emergency technicians burst through the doors, pushing a stretcher into the crowded E.R. Their walkie-talkies dangled from their shoulders, squawking and hissing like demented parrots. The triage nurse directed them straight into a room as the E.M.T.’s barked out what they knew. “Sixty-four-year-old man . . . history of a stroke . . . complaints of weakness and belly pain.” His heart was slow, they reported; his blood pressure so low that it was immeasurable. The monitor showed a heart rate in the 20s — normal is over 60. Dr. Bernd Woerner strode in and quickly assessed the situation. “Get me an amp of atropine,” he snapped, calling for the medicine used to speed up the heart.
The doctor watched as the monitor screen continued its flat yellow line, broken only occasionally by the spike indicating another heartbeat. Slowly the patient’s heart rate and blood pressure began to rise.
Throughout all this the patient was alert, Woerner told me later. He explained to the patient, “Your heart is pumping too slowly.” The medicine would keep his heart rate up until the cardiologist arrived in an hour or so to insert a pacemaker. In the meantime, they had to begin to figure out what was wrong with his heart.
I knew this patient. I was his internist and had been seeing him for the past year, since he had his stroke. Before that, he hadn’t been to a doctor for decades. He came to me when the massive stroke rendered his right leg and arm nearly motionless, his face crooked and his speech slurred. Still, his beautiful cockeyed smile and gallant manner made him a favorite at our office. He often brought us gifts — candy or some of the pecans sent from his family in North Carolina. He was doing well, so I was shocked when I got word from the E.R. that my patient was dying. And the doctors there weren’t sure why.
With the usual chaos of the emergency room boiling around them, Woerner forced himself to sit quietly as the patient described his symptoms. The man spoke in an unnaturally deliberate drawl, as if in slow motion: “I — can’t — walk.” It started the night before. He felt weak, could barely move. Any chest pain? Woerner broke in. Shortness of breath? Fever or chills? Vomiting? The patient shook his head no. He was taking medications to lower his blood pressure and cholesterol. He had not smoked or drunk alcohol since his stroke. Examining him, Woerner saw the results of the stroke but little more.
2. Investigation
Why was his heart beating so slowly? the doctor wondered. Had he taken too much of one of his medications? Had he suffered a heart attack that affected the natural pacemaker in his heart?
Part of the answer came less than an hour later. The lab called to report that the patient’s kidneys weren’t working. And his potassium — an essential element in body chemistry, regulated by the kidneys — was dangerously high. Potassium controls how easily a cell responds to the body’s commands. Too little potassium, and the cells overreact to any stimulation; too much, and the body slows down. The patient was given a medicine to get the potassium out of his system and then transferred to the I.C.U. for monitoring.
If the potassium was high because of his kidney failure, what had caused his kidneys to fail? Dr. Perry Smith, the intern on call in the I.C.U., gnawed at this question as he reviewed the chart and examined the patient. It wasn’t a drug error. The patient’s medication box showed the correct number of pills. And it hadn’t been a heart attack; a blood test proved that. Smith looked for the results of the urinalysis to see if there was any clue there. Somehow no one had sent any urine to the lab. Were his kidneys too damaged to produce urine? That would be important to know. Smith asked the nurse to get some urine from the patient.
She returned empty-handed. The patient couldn’t urinate, and she hadn’t been able to insert a Foley catheter, a rubber tube that is passed through the urethra into the bladder to collect urine. Was something blocking the urethra? A urology resident finally managed to get a catheter into the bladder. Urine gushed out — nearly half a gallon of it. A full bladder normally holds only a quarter of that. The urology resident looked at the intern: “I guess now we know why his kidneys weren’t working.”
3. Resolution
The urethra was blocked — by the prostate gland. The prostate surrounds the urethra, and when it enlarges, as it often does with age, it impinges on the narrow outlet, obstructing and ultimately blocking it so that no urine can pass. As the trapped liquid filled the bladder, the pressure shut down the patient’s kidneys.
Just hours after the obstruction was relieved, his potassium began to drop as the kidneys went back to work. Four hours later, the patient’s heart rate was up over 60. By the next morning, the abdominal pain, probably caused by his hugely distended bladder, had eased. When he left the hospital three days later, his potassium and heart rate were normal and his kidneys, nearly so. He would have to keep the tube in his bladder until his prostate could be removed.
I was out of town that first day and had to follow my patient’s progress by telephone. When I heard that the prostate was the cause of the life-threatening bradycardia, I felt as if I had been punched in the chest. This was something I should have caught and didn’t. An internist’s job is to diagnose and treat acute illness and screen for and prevent additional disease. I joke with the residents I teach that it is our responsibility to keep our patients healthy and out of the hospital. If so, I had failed.
Screening for disease has two parts: usually a physical exam and what is known as a review of systems, a set of questions used to elicit symptoms of a disease the patient is at risk for. This patient, with his high blood pressure, high cholesterol and stroke, would be at risk for a heart attack, another stroke and, like many men his age, prostate problems. I should have asked about these at every visit and once a year done a rectal exam to assess prostate size and look for cancer. From reviewing the patient’s chart, it appeared I had limited my attention and my exam to his immediate problems — overlooking some of the other risks he faced.
I had asked him if he had problems urinating, and he had said no. I don’t think he was lying; I think he assumed that his bathroom difficulty was just one more skill stolen from him by his stroke. So much of the damage from that cerebral vascular accident was clearly visible and public. I suspect he felt that this disability, at least, could remain private.
And when he didn’t acknowledge any difficulties, I was happy to allow our visits to focus on getting his blood pressure and cholesterol under control, educating him on his medical problems, managing his meds and arranging his transportation and rehab. Everything else I treated as a long-term goal, to be attended to once these very pressing short-term needs were managed. Understandable perhaps, but it almost killed him. Practicing medicine is a balancing act — weighing immediate and long-term good. His case was a vivid reminder of what can happen when that balance is lost.
I didn’t visit my patient in the hospital. Normally I would have, but I was worried that he would be as angry with me as I was with myself. I saw him the following week. “I’m so sorry,” I started. He smiled his magnificent smile and squeezed my hand. “No matter,” he said, his words still slurred but back to their normal rhythm. He reached into his pocket, produced a few of his pecans from North Carolina and offered them to me. I took them gratefully. Perhaps I could be forgiven.
The emergency technicians burst through the doors, pushing a stretcher into the crowded E.R. Their walkie-talkies dangled from their shoulders, squawking and hissing like demented parrots. The triage nurse directed them straight into a room as the E.M.T.’s barked out what they knew. “Sixty-four-year-old man . . . history of a stroke . . . complaints of weakness and belly pain.” His heart was slow, they reported; his blood pressure so low that it was immeasurable. The monitor showed a heart rate in the 20s — normal is over 60. Dr. Bernd Woerner strode in and quickly assessed the situation. “Get me an amp of atropine,” he snapped, calling for the medicine used to speed up the heart.
The doctor watched as the monitor screen continued its flat yellow line, broken only occasionally by the spike indicating another heartbeat. Slowly the patient’s heart rate and blood pressure began to rise.
Throughout all this the patient was alert, Woerner told me later. He explained to the patient, “Your heart is pumping too slowly.” The medicine would keep his heart rate up until the cardiologist arrived in an hour or so to insert a pacemaker. In the meantime, they had to begin to figure out what was wrong with his heart.
I knew this patient. I was his internist and had been seeing him for the past year, since he had his stroke. Before that, he hadn’t been to a doctor for decades. He came to me when the massive stroke rendered his right leg and arm nearly motionless, his face crooked and his speech slurred. Still, his beautiful cockeyed smile and gallant manner made him a favorite at our office. He often brought us gifts — candy or some of the pecans sent from his family in North Carolina. He was doing well, so I was shocked when I got word from the E.R. that my patient was dying. And the doctors there weren’t sure why.
With the usual chaos of the emergency room boiling around them, Woerner forced himself to sit quietly as the patient described his symptoms. The man spoke in an unnaturally deliberate drawl, as if in slow motion: “I — can’t — walk.” It started the night before. He felt weak, could barely move. Any chest pain? Woerner broke in. Shortness of breath? Fever or chills? Vomiting? The patient shook his head no. He was taking medications to lower his blood pressure and cholesterol. He had not smoked or drunk alcohol since his stroke. Examining him, Woerner saw the results of the stroke but little more.
2. Investigation
Why was his heart beating so slowly? the doctor wondered. Had he taken too much of one of his medications? Had he suffered a heart attack that affected the natural pacemaker in his heart?
Part of the answer came less than an hour later. The lab called to report that the patient’s kidneys weren’t working. And his potassium — an essential element in body chemistry, regulated by the kidneys — was dangerously high. Potassium controls how easily a cell responds to the body’s commands. Too little potassium, and the cells overreact to any stimulation; too much, and the body slows down. The patient was given a medicine to get the potassium out of his system and then transferred to the I.C.U. for monitoring.
If the potassium was high because of his kidney failure, what had caused his kidneys to fail? Dr. Perry Smith, the intern on call in the I.C.U., gnawed at this question as he reviewed the chart and examined the patient. It wasn’t a drug error. The patient’s medication box showed the correct number of pills. And it hadn’t been a heart attack; a blood test proved that. Smith looked for the results of the urinalysis to see if there was any clue there. Somehow no one had sent any urine to the lab. Were his kidneys too damaged to produce urine? That would be important to know. Smith asked the nurse to get some urine from the patient.
She returned empty-handed. The patient couldn’t urinate, and she hadn’t been able to insert a Foley catheter, a rubber tube that is passed through the urethra into the bladder to collect urine. Was something blocking the urethra? A urology resident finally managed to get a catheter into the bladder. Urine gushed out — nearly half a gallon of it. A full bladder normally holds only a quarter of that. The urology resident looked at the intern: “I guess now we know why his kidneys weren’t working.”
3. Resolution
The urethra was blocked — by the prostate gland. The prostate surrounds the urethra, and when it enlarges, as it often does with age, it impinges on the narrow outlet, obstructing and ultimately blocking it so that no urine can pass. As the trapped liquid filled the bladder, the pressure shut down the patient’s kidneys.
Just hours after the obstruction was relieved, his potassium began to drop as the kidneys went back to work. Four hours later, the patient’s heart rate was up over 60. By the next morning, the abdominal pain, probably caused by his hugely distended bladder, had eased. When he left the hospital three days later, his potassium and heart rate were normal and his kidneys, nearly so. He would have to keep the tube in his bladder until his prostate could be removed.
I was out of town that first day and had to follow my patient’s progress by telephone. When I heard that the prostate was the cause of the life-threatening bradycardia, I felt as if I had been punched in the chest. This was something I should have caught and didn’t. An internist’s job is to diagnose and treat acute illness and screen for and prevent additional disease. I joke with the residents I teach that it is our responsibility to keep our patients healthy and out of the hospital. If so, I had failed.
Screening for disease has two parts: usually a physical exam and what is known as a review of systems, a set of questions used to elicit symptoms of a disease the patient is at risk for. This patient, with his high blood pressure, high cholesterol and stroke, would be at risk for a heart attack, another stroke and, like many men his age, prostate problems. I should have asked about these at every visit and once a year done a rectal exam to assess prostate size and look for cancer. From reviewing the patient’s chart, it appeared I had limited my attention and my exam to his immediate problems — overlooking some of the other risks he faced.
I had asked him if he had problems urinating, and he had said no. I don’t think he was lying; I think he assumed that his bathroom difficulty was just one more skill stolen from him by his stroke. So much of the damage from that cerebral vascular accident was clearly visible and public. I suspect he felt that this disability, at least, could remain private.
And when he didn’t acknowledge any difficulties, I was happy to allow our visits to focus on getting his blood pressure and cholesterol under control, educating him on his medical problems, managing his meds and arranging his transportation and rehab. Everything else I treated as a long-term goal, to be attended to once these very pressing short-term needs were managed. Understandable perhaps, but it almost killed him. Practicing medicine is a balancing act — weighing immediate and long-term good. His case was a vivid reminder of what can happen when that balance is lost.
I didn’t visit my patient in the hospital. Normally I would have, but I was worried that he would be as angry with me as I was with myself. I saw him the following week. “I’m so sorry,” I started. He smiled his magnificent smile and squeezed my hand. “No matter,” he said, his words still slurred but back to their normal rhythm. He reached into his pocket, produced a few of his pecans from North Carolina and offered them to me. I took them gratefully. Perhaps I could be forgiven.
Saturday, April 21, 2007
FDA: No evidence aspartame causes cancer
A federal review of a 2005 Italian study found no data to support the conclusion the sugar substitute aspartame causes cancer, a health official said Friday.
The Food and Drug Administration has not seen scientific information that would support a change in its conclusions about the safety of aspartame, said Laura Tarantino, director of the agency's Office of Food Additive Safety. In 1981, the FDA determined that aspartame was safe for use in food.
The Italian study concluded aspartame led to higher rates of lymphoma and leukemia in rats. However, the European Food Safety Authority reviewed the data and said it did not support the study's conclusions. The European agency reiterated its previously held position that the low-calorie sweetener is safe.
The FDA then conducted its own review of the study, despite not receiving additional data it had requested.
"Our conclusion, based on a comprehensive review of all data we had, is there is no evidence that aspartame is a carcinogen or any evidence to change our previous conclusion: that aspartame, the way it is used, is safe," Tarantino said. The agency plans to release its review shortly, she said.
Meanwhile, the Italian team is expected to release Monday the results of a further study of the sweetener.
Aspartame has been sold for 25 years. It's found in thousands of products, including sodas, chewing gum, dairy products and even some medicines. NutraSweet and Equal are popular brands.
The Food and Drug Administration has not seen scientific information that would support a change in its conclusions about the safety of aspartame, said Laura Tarantino, director of the agency's Office of Food Additive Safety. In 1981, the FDA determined that aspartame was safe for use in food.
The Italian study concluded aspartame led to higher rates of lymphoma and leukemia in rats. However, the European Food Safety Authority reviewed the data and said it did not support the study's conclusions. The European agency reiterated its previously held position that the low-calorie sweetener is safe.
The FDA then conducted its own review of the study, despite not receiving additional data it had requested.
"Our conclusion, based on a comprehensive review of all data we had, is there is no evidence that aspartame is a carcinogen or any evidence to change our previous conclusion: that aspartame, the way it is used, is safe," Tarantino said. The agency plans to release its review shortly, she said.
Meanwhile, the Italian team is expected to release Monday the results of a further study of the sweetener.
Aspartame has been sold for 25 years. It's found in thousands of products, including sodas, chewing gum, dairy products and even some medicines. NutraSweet and Equal are popular brands.
Enoxaparin Outdoes Heparin for Post-Stroke Venous Thromboembolism
SAN ANTONIO, Tex., April 20 -- Enoxaparin (Lovenox), a low molecular-weight heparin, proved more effective than unfractionated heparin for preventing potentially fatal leg and lung clots after acute ischemic stroke, researchers reported.
In a head-to-head study of 1,762 stroke patients unable to walk unassisted, enoxaparin was 43% more effective at preventing venous thromboembolism than unfractionated heparin, David G. Sherman, M.D., of the University of Texas here, and colleagues reported in the Apil 21 issue of The Lancet.
The results of this study, Dr. Sherman concluded, suggest that for patients with acute ischemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits-to-risk ratio and convenience of once daily administration.
Venous thrombembolism with either low-molecular-weight heparin or unfractionated heparin is recommended for acute ischemic stroke, but because large studies are lacking, it has been uncertain which is the better regimen, Dr. Sherman said.
To compare the efficacy and safety of the drugs, the researchers undertook a large, 15-nation multinational randomized study (PREVAIL), sponsored by Sanofi-Aventis, maker of enoxaparin.
Within 48 hours of symptoms, 666 patients were given enoxaparin (40 mg subcutaneously) once daily for 10 days, while 669 got unfractionated heparin (5,000 U subcutaneously) every 12 hours, for 10 days (range for all, six to 14 days).
The patients were stratified by the National Institutes of Health Stroke Scale (NIHSS) (severe stroke ≥14, less severe stroke <14).
Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] versus 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, P=0.0001; difference -7.9%, -11.6 to -4.2).
The greater reduction with enoxaparin was consistent for patients with an NIHSS score of 14 or more (26 [16%] versus 52 [30%]; P=0.0036) or less than 14 (42 [8%] versus 69 [14%]; P=0.0044).
In a head-to-head study of 1,762 stroke patients unable to walk unassisted, enoxaparin was 43% more effective at preventing venous thromboembolism than unfractionated heparin, David G. Sherman, M.D., of the University of Texas here, and colleagues reported in the Apil 21 issue of The Lancet.
The results of this study, Dr. Sherman concluded, suggest that for patients with acute ischemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits-to-risk ratio and convenience of once daily administration.
Venous thrombembolism with either low-molecular-weight heparin or unfractionated heparin is recommended for acute ischemic stroke, but because large studies are lacking, it has been uncertain which is the better regimen, Dr. Sherman said.
To compare the efficacy and safety of the drugs, the researchers undertook a large, 15-nation multinational randomized study (PREVAIL), sponsored by Sanofi-Aventis, maker of enoxaparin.
Within 48 hours of symptoms, 666 patients were given enoxaparin (40 mg subcutaneously) once daily for 10 days, while 669 got unfractionated heparin (5,000 U subcutaneously) every 12 hours, for 10 days (range for all, six to 14 days).
The patients were stratified by the National Institutes of Health Stroke Scale (NIHSS) (severe stroke ≥14, less severe stroke <14).
Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] versus 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, P=0.0001; difference -7.9%, -11.6 to -4.2).
The greater reduction with enoxaparin was consistent for patients with an NIHSS score of 14 or more (26 [16%] versus 52 [30%]; P=0.0036) or less than 14 (42 [8%] versus 69 [14%]; P=0.0044).
Flu Epidemics Linked to Surge in Coronary Heart Disease Deaths
HOUSTON, April 20 -- A large percentage of influenza deaths are the result of disease-triggered acute myocardial infarctions, researchers here reported on the basis of autopsy-proven data.
In a week during a flu epidemic, the chances of dying of a heart attack increased by 30% and of dying of chronic ischemic heart disease by 10%, reported Mohammad Madjid, M.D., of the University of Texas here, and colleagues, online in the European Heart Journal.
Influenza causes up to an estimated 92,000 U.S. deaths a year as a result of myocardial infarction alone, they reported on the basis of their clinical observations and analyses of published trials.
Many of these deaths could be prevented if every high-risk patient had an annual flu shot. Dr. Madjid and colleagues wrote.
Working with Russian colleagues at the St. Petersburg Medical Academy, the researchers studied the impact of influenza on coronary deaths (acute myocardial infarction and chronic ischemic heart disease) in autopsies conducted from 1993 to 2000 in St. Petersburg.
In a week during a flu epidemic, the chances of dying of a heart attack increased by 30% and of dying of chronic ischemic heart disease by 10%, reported Mohammad Madjid, M.D., of the University of Texas here, and colleagues, online in the European Heart Journal.
Influenza causes up to an estimated 92,000 U.S. deaths a year as a result of myocardial infarction alone, they reported on the basis of their clinical observations and analyses of published trials.
Many of these deaths could be prevented if every high-risk patient had an annual flu shot. Dr. Madjid and colleagues wrote.
Working with Russian colleagues at the St. Petersburg Medical Academy, the researchers studied the impact of influenza on coronary deaths (acute myocardial infarction and chronic ischemic heart disease) in autopsies conducted from 1993 to 2000 in St. Petersburg.
Scientists find one reason why bladder cancer hits more men
Scientists have discovered one of the reasons why bladder cancer is so much more prevalent in men than women: A molecular receptor or protein that is much more active in men than women plays a role in the development of the disease. The finding could open the door to new types of treatment with the disease.
In an article in the April 4 issue of the Journal of the National Cancer Institute, Chawnshang Chang, Ph.D., of the University of Rochester Medical Center and colleagues show that the androgen receptor, which is central to the action of testosterone and other hormones that are much more plentiful in men than women, appears to play a key role in the disease.
In experiments reported in the journal, mice without the receptor had dramatically lower rates of bladder cancer compared to normal mice with the receptor, and human cancer cells with the receptor were much more aggressive than those without it. Mice develop bladder cancer for many of the same reasons people do, and the molecular signals that control cancer development in mice mirror those in humans.
The disease hits about three times as many men as women, including estimates of 50,000 men and 17,000 women in the United States in 2007, according to the American Cancer Society. Some scientists have suspected that male hormones working in concert with the androgen receptor might play a role, but hard evidence has been minimal until now, said Edward Messing, M.D., a bladder cancer expert and chair of Urology. Instead, scientists have suspected that factors like greater exposure of men to cigarettes and industrial chemicals has been responsible.
In an article in the April 4 issue of the Journal of the National Cancer Institute, Chawnshang Chang, Ph.D., of the University of Rochester Medical Center and colleagues show that the androgen receptor, which is central to the action of testosterone and other hormones that are much more plentiful in men than women, appears to play a key role in the disease.
In experiments reported in the journal, mice without the receptor had dramatically lower rates of bladder cancer compared to normal mice with the receptor, and human cancer cells with the receptor were much more aggressive than those without it. Mice develop bladder cancer for many of the same reasons people do, and the molecular signals that control cancer development in mice mirror those in humans.
The disease hits about three times as many men as women, including estimates of 50,000 men and 17,000 women in the United States in 2007, according to the American Cancer Society. Some scientists have suspected that male hormones working in concert with the androgen receptor might play a role, but hard evidence has been minimal until now, said Edward Messing, M.D., a bladder cancer expert and chair of Urology. Instead, scientists have suspected that factors like greater exposure of men to cigarettes and industrial chemicals has been responsible.
Susceptibility to Crohn's disease -- an important new clue
Press release from PLoS Genetics
Crohn’s disease is a chronic relapsing inflammatory disorder of the intestinal tract that affects an estimated 0.15% of people in the developed world. Common symptoms include abdominal pain and diarrhea, but the disorder is often associated with debilitating clinical complications. Researchers from the University of Liège, Belgium, have now uncovered an important clue to the susceptibility of individuals to this disease.
In a genome-wide association study with more than 300,000 single nucleotide polymorphisms (SNPs) – DNA sequence variations occurring when a single nucleotide in the genome differs between members of a species – Cécile Libioulle et al. identified a new susceptibility locus for Crohn’s disease. Their results are published online in the open-access journal PLoS Genetics.
Recent advances in SNP genotyping technology have allowed systematic association scanning of the entire genome for the detection of novel susceptibility loci – fixed positions on a chromosome, such as the position of a gene. Libioulle and colleagues applied this approach to Crohn’s disease and identified the key locus on chromosome 5.
Individual susceptibility to many common diseases, including Crohn’s disease, is determined by a combination of environmental and genetic factors and identifying these genetic risk factors is one of the most important objectives of modern medical genetics, potentially paving the way towards personalized medicine and drug target identification.
Crohn’s disease is a chronic relapsing inflammatory disorder of the intestinal tract that affects an estimated 0.15% of people in the developed world. Common symptoms include abdominal pain and diarrhea, but the disorder is often associated with debilitating clinical complications. Researchers from the University of Liège, Belgium, have now uncovered an important clue to the susceptibility of individuals to this disease.
In a genome-wide association study with more than 300,000 single nucleotide polymorphisms (SNPs) – DNA sequence variations occurring when a single nucleotide in the genome differs between members of a species – Cécile Libioulle et al. identified a new susceptibility locus for Crohn’s disease. Their results are published online in the open-access journal PLoS Genetics.
Recent advances in SNP genotyping technology have allowed systematic association scanning of the entire genome for the detection of novel susceptibility loci – fixed positions on a chromosome, such as the position of a gene. Libioulle and colleagues applied this approach to Crohn’s disease and identified the key locus on chromosome 5.
Individual susceptibility to many common diseases, including Crohn’s disease, is determined by a combination of environmental and genetic factors and identifying these genetic risk factors is one of the most important objectives of modern medical genetics, potentially paving the way towards personalized medicine and drug target identification.
Friday, April 20, 2007
Shooting shows gaps in mental health safety net
CHICAGO (Reuters) - Mental health professionals complain their hands are tied in two ways when they try to help people like Virginia Tech gunman Cho Seung-Hui -- a lack of funding for mental health services in general, and laws that makes it tough to treat people against their will.
They say the 23-year-old student's shooting rampage sheds new light on flaws in the U.S. mental health system.
"Our mental health system failed this young man," said Jill Bolte Taylor, a brain researcher at Indiana University School of Medicine in Bloomington, Indiana.
Cho drew the attention of campus police in late 2005 amid complaints that he was annoying women students. He spent some time in a psychiatric hospital because of worries he was suicidal.
"Funding for mental health services in the United States has dropped in half over the past 25 years," Dr. Christopher Flynn, director of Virginia Tech's Thomas Cook Counseling Center, told a news conference.
"We have seen, every time there's a cut in public health funding, the first people that are cut are mental health providers, and we do our entire system a disservice by continuing to do that."
Dr. Steven Sharfstein, past president of the American Psychiatric Association, said the problems are both financial and legal.
"What was a red flag for me is that he was seen in a mental health facility and held for one day. That is a symptom of the dysfunction of our mental health system," said Sharfstein, who is president of Sheppard Pratt Health System in Baltimore.
"If someone isn't readily seen as imminently dangerous, there is no time and money set aside to do a more in-depth and effective diagnosis. He may have been hiding a paranoid psychosis that with a few days of observation might have come out."
They say the 23-year-old student's shooting rampage sheds new light on flaws in the U.S. mental health system.
"Our mental health system failed this young man," said Jill Bolte Taylor, a brain researcher at Indiana University School of Medicine in Bloomington, Indiana.
Cho drew the attention of campus police in late 2005 amid complaints that he was annoying women students. He spent some time in a psychiatric hospital because of worries he was suicidal.
"Funding for mental health services in the United States has dropped in half over the past 25 years," Dr. Christopher Flynn, director of Virginia Tech's Thomas Cook Counseling Center, told a news conference.
"We have seen, every time there's a cut in public health funding, the first people that are cut are mental health providers, and we do our entire system a disservice by continuing to do that."
Dr. Steven Sharfstein, past president of the American Psychiatric Association, said the problems are both financial and legal.
"What was a red flag for me is that he was seen in a mental health facility and held for one day. That is a symptom of the dysfunction of our mental health system," said Sharfstein, who is president of Sheppard Pratt Health System in Baltimore.
"If someone isn't readily seen as imminently dangerous, there is no time and money set aside to do a more in-depth and effective diagnosis. He may have been hiding a paranoid psychosis that with a few days of observation might have come out."
Doctors Try New Surgery for Gallbladder Removal
Doctors in New York have removed a woman’s gallbladder with instruments passed through her vagina, a technique they hope will cause less pain and scarring than the usual operation, and allow a quicker recovery. The technique can eliminate the need to cut through abdominal muscles, a major source of pain after surgery.
The operation was experimental, part of a study that is being done to find out whether people will fare better if abdominal surgery is performed through natural openings in the body rather than cuts in the belly. The surgery still requires cutting, through the wall of the vagina, stomach or colon, but doctors say it should hurt less because those tissues are far less sensitive than the abdominal muscles.
Interest in this idea heightened after doctors from India made a video in 2004 showing an appendix being taken out through a patient’s mouth. The patient had abdominal scars that would have made conventional surgery difficult.
The New York patient, 66, had her gallbladder removed on March 21 and is recovering well, said her surgeon, Dr. Marc Bessler, the director of laparoscopic surgery at Columbia University Medical Center. Dr. Bessler said he thought it was the first time the operation had been performed in the United States, and he plans to show a video of the operation at a gastroenterology meeting in Las Vegas on Sunday.
“Going through a natural orifice, the mouth or rectum or vagina, to get into the abdomen and do an operation, is being excitedly worked on by a whole lot of people,” Dr. Bessler said, adding that companies were beginning to make special surgical tools for the operations and that doctors had formed an organization called Noscar (www.Noscar.org), which stands for Natural Orifice Surgery Consortium for Assessment and Research.
The idea is part of a broader trend to make surgery less and less invasive. In the late 1980s and early ’90s, surgeons began removing gallbladders with laparoscopic surgery, performed through a few small slits in the belly for a camera and surgical tools instead of the 10-inch incision needed for the original, open operation. Although some doctors were skeptical at first about the laparoscopic approach, it soon caught on, and now accounts for 90 percent of gallbladder operations.
“But patients still have pain, recovery time and scars,” Dr. Bessler said. “The next phase to make it better is to eliminate the remaining causes of pain — incisions and instruments that have to go through the muscles of the abdominal wall.”
The operation was experimental, part of a study that is being done to find out whether people will fare better if abdominal surgery is performed through natural openings in the body rather than cuts in the belly. The surgery still requires cutting, through the wall of the vagina, stomach or colon, but doctors say it should hurt less because those tissues are far less sensitive than the abdominal muscles.
Interest in this idea heightened after doctors from India made a video in 2004 showing an appendix being taken out through a patient’s mouth. The patient had abdominal scars that would have made conventional surgery difficult.
The New York patient, 66, had her gallbladder removed on March 21 and is recovering well, said her surgeon, Dr. Marc Bessler, the director of laparoscopic surgery at Columbia University Medical Center. Dr. Bessler said he thought it was the first time the operation had been performed in the United States, and he plans to show a video of the operation at a gastroenterology meeting in Las Vegas on Sunday.
“Going through a natural orifice, the mouth or rectum or vagina, to get into the abdomen and do an operation, is being excitedly worked on by a whole lot of people,” Dr. Bessler said, adding that companies were beginning to make special surgical tools for the operations and that doctors had formed an organization called Noscar (www.Noscar.org), which stands for Natural Orifice Surgery Consortium for Assessment and Research.
The idea is part of a broader trend to make surgery less and less invasive. In the late 1980s and early ’90s, surgeons began removing gallbladders with laparoscopic surgery, performed through a few small slits in the belly for a camera and surgical tools instead of the 10-inch incision needed for the original, open operation. Although some doctors were skeptical at first about the laparoscopic approach, it soon caught on, and now accounts for 90 percent of gallbladder operations.
“But patients still have pain, recovery time and scars,” Dr. Bessler said. “The next phase to make it better is to eliminate the remaining causes of pain — incisions and instruments that have to go through the muscles of the abdominal wall.”
Full-Strength Aspirin Over Time Has Ambiguous Effect on Cancer Risk
ATLANTA, April 10 -- Five years or more of daily adult-strength aspirin is associated with modest protection against colorectal, prostate, and breast cancers, investigators here reported.
However, daily low-dose aspirin (81 mg) used for cardiovascular protection is not associated with any additional protection against cancer, in keeping with other studies, reported Eric J. Jacobs, Ph.D., of the American Cancer Society, and colleagues, in the April 18 issue of the Journal of the National Cancer Institute.
The five-year findings emerged from a huge observational survey. But the investigators cautioned that a decade or longer will be needed to determine whether the association they found matters. At the moment, they wrote, "our results do not have immediate clinical implications."
In an accompanying editorial, María Elena Martínez, M.P.H., Ph.D., of the University of Arizona in Tucson, and E. Robert Greenberg, M.D., of Dartmouth Medical College in Hanover, N.H., pointed out that chronic use of full-strength aspirin (325 mg) may also have GI and hematologic consequences that obviate any potential anticancer benefit that may emerge in a long-term trial.
"Although such a trial merits careful consideration, it might be difficult to conduct it among average-risk individuals, given the toxicity of aspirin at doses greater than 80 mg/day," they wrote. "Thus, the authors appear justified in concluding that their results do not have immediate clinical implications, but they clearly illustrate the potential future importance of aspirin and other anti-inflammatory interventions as cancer control strategies."
However, daily low-dose aspirin (81 mg) used for cardiovascular protection is not associated with any additional protection against cancer, in keeping with other studies, reported Eric J. Jacobs, Ph.D., of the American Cancer Society, and colleagues, in the April 18 issue of the Journal of the National Cancer Institute.
The five-year findings emerged from a huge observational survey. But the investigators cautioned that a decade or longer will be needed to determine whether the association they found matters. At the moment, they wrote, "our results do not have immediate clinical implications."
In an accompanying editorial, María Elena Martínez, M.P.H., Ph.D., of the University of Arizona in Tucson, and E. Robert Greenberg, M.D., of Dartmouth Medical College in Hanover, N.H., pointed out that chronic use of full-strength aspirin (325 mg) may also have GI and hematologic consequences that obviate any potential anticancer benefit that may emerge in a long-term trial.
"Although such a trial merits careful consideration, it might be difficult to conduct it among average-risk individuals, given the toxicity of aspirin at doses greater than 80 mg/day," they wrote. "Thus, the authors appear justified in concluding that their results do not have immediate clinical implications, but they clearly illustrate the potential future importance of aspirin and other anti-inflammatory interventions as cancer control strategies."
Why cisplatin kills breast cancer cells when other drugs fail
The cancerous cells of some individuals with breast cancer lack expression of two cell surface proteins, the estrogen and progesterone receptors, and do not express increased amounts of HER2. Individuals with such breast cancer (known as triple-negative breast cancer) do not respond to treatment with commonly used chemotherapeutic drugs and their prognosis is relatively poor. But now, a new study from researchers at Massachusetts General Hospital Cancer Center, Boston, has indicated that triple-negative breast cancer cell lines are sensitive to exposure to the chemotherapeutic cisplatin.
In the study, which appears online on April 19 in advance of publication in the May print issue of the Journal of Clinical Investigation, Leif Ellisen and colleagues show that triple-negative breast cancer specimens express increased amounts of two proteins, delta-Np63 and TAp73. Delta-Np63 was shown to bind TAp73 and prevent it from killing the cancerous cells. Importantly, the chemotherapeutic drug cisplatin, but not other commonly used chemotherapeutic drugs, was found to release TAp73 from delta-Np63, causing the cells to be killed. This study indicates that individuals with triple-negative breast cancer might benefit from early treatment with cisplatin if their cancerous cells express increased amounts of delta-Np63 and TAp73.
In the study, which appears online on April 19 in advance of publication in the May print issue of the Journal of Clinical Investigation, Leif Ellisen and colleagues show that triple-negative breast cancer specimens express increased amounts of two proteins, delta-Np63 and TAp73. Delta-Np63 was shown to bind TAp73 and prevent it from killing the cancerous cells. Importantly, the chemotherapeutic drug cisplatin, but not other commonly used chemotherapeutic drugs, was found to release TAp73 from delta-Np63, causing the cells to be killed. This study indicates that individuals with triple-negative breast cancer might benefit from early treatment with cisplatin if their cancerous cells express increased amounts of delta-Np63 and TAp73.
Drinking heavily in college may lead to heart disease later in life
American Heart Association meeting report
College-age students who drink heavily may increase their risk for future heart disease, researchers reported at the American Heart Association's 8th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology.
In a small study, Minnesota researchers found that a group of college students who drank heavily had higher levels of C-reactive protein (CRP), a blood marker for inflammation that can increase the risk for heart disease. Increased CRP placed heavy drinkers at moderate risk for cardiovascular disease in early adulthood. Moderate drinkers had the lowest CRP levels.
"These students may be setting themselves up for an increased risk for cardiovascular disease," said Elizabeth Donovan, lead researcher of the study and an undergraduate student at the College of Saint Benedict in St. Joseph, Minn. "This highlights an additional reason to be concerned about heavy drinking in college-age individuals." While most studies of alcohol and CRP levels have focused on older people, this small study examined individuals in early adulthood.
"If high CRP levels are recognized at an early age, the person has a chance to make healthier lifestyle choices," Donovan said.
Twenty-five college-age individuals completed surveys that assessed factors that can affect CRP levels such as alcohol consumption patterns, medication use, smoking habits and recent weight loss. Researchers assigned the students to one of three groups:
non-drinkers, meaning they consumed one or less drinks one day a week;
moderate drinkers, who consumed two to five drinks of alcohol on a typical drinking day, one to two days a week; and
heavy drinkers, who consumed three or more drinks at least three or more days a week or consumed five or more drinks in one sitting at least two or more days a week.
One drink was equal to 12 ounces of beer, five ounces of wine or 1.5 ounces of hard alcohol.
Students on oral contraceptives, hormone therapy, cholesterol-lowering therapy or who had a significant recent weight loss were excluded from the study.
The average CRP for students in the study was 0.9 milligrams per liter (mg/L), placing the group as a whole at low risk. CRP levels less than 1 mg/L are associated with low risk for cardiovascular disease. CRP levels between 1 and 3 mg/L are associated with moderate risk and CRP levels above 3 mg/L are associated with high risk for future cardiovascular disease.
College-age students who drink heavily may increase their risk for future heart disease, researchers reported at the American Heart Association's 8th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology.
In a small study, Minnesota researchers found that a group of college students who drank heavily had higher levels of C-reactive protein (CRP), a blood marker for inflammation that can increase the risk for heart disease. Increased CRP placed heavy drinkers at moderate risk for cardiovascular disease in early adulthood. Moderate drinkers had the lowest CRP levels.
"These students may be setting themselves up for an increased risk for cardiovascular disease," said Elizabeth Donovan, lead researcher of the study and an undergraduate student at the College of Saint Benedict in St. Joseph, Minn. "This highlights an additional reason to be concerned about heavy drinking in college-age individuals." While most studies of alcohol and CRP levels have focused on older people, this small study examined individuals in early adulthood.
"If high CRP levels are recognized at an early age, the person has a chance to make healthier lifestyle choices," Donovan said.
Twenty-five college-age individuals completed surveys that assessed factors that can affect CRP levels such as alcohol consumption patterns, medication use, smoking habits and recent weight loss. Researchers assigned the students to one of three groups:
non-drinkers, meaning they consumed one or less drinks one day a week;
moderate drinkers, who consumed two to five drinks of alcohol on a typical drinking day, one to two days a week; and
heavy drinkers, who consumed three or more drinks at least three or more days a week or consumed five or more drinks in one sitting at least two or more days a week.
One drink was equal to 12 ounces of beer, five ounces of wine or 1.5 ounces of hard alcohol.
Students on oral contraceptives, hormone therapy, cholesterol-lowering therapy or who had a significant recent weight loss were excluded from the study.
The average CRP for students in the study was 0.9 milligrams per liter (mg/L), placing the group as a whole at low risk. CRP levels less than 1 mg/L are associated with low risk for cardiovascular disease. CRP levels between 1 and 3 mg/L are associated with moderate risk and CRP levels above 3 mg/L are associated with high risk for future cardiovascular disease.
Green tea may help prevent autoimmune diseases
Green tea may help protect against autoimmune disease, Medical College of Georgia researchers say.
Researchers studied an animal model for type I diabetes and primary Sjogren's Syndrome, which damages the glands that produce tears and saliva.
They found significantly less salivary gland damage in a group treated with green tea extract, suggesting a reduction of the Sjogren's symptom commonly referred to as dry mouth. Dry mouth can also be caused by certain drugs, radiation and other diseases.
Approximately 30 percent of elderly Americans suffer from degrees of dry mouth, says Dr. Stephen Hsu, a researcher in the MCG School of Dentistry and lead investigator on the study. Only 5 percent of the elderly in China, where green tea is widely consumed, suffer from the problem.
"Since it is an autoimmune disease, Sjogren's Syndrome causes the body to attack itself and produce extra antibodies that mistakenly target the salivary and lacrimal glands," he says.
Researchers studied an animal model for type I diabetes and primary Sjogren's Syndrome, which damages the glands that produce tears and saliva.
They found significantly less salivary gland damage in a group treated with green tea extract, suggesting a reduction of the Sjogren's symptom commonly referred to as dry mouth. Dry mouth can also be caused by certain drugs, radiation and other diseases.
Approximately 30 percent of elderly Americans suffer from degrees of dry mouth, says Dr. Stephen Hsu, a researcher in the MCG School of Dentistry and lead investigator on the study. Only 5 percent of the elderly in China, where green tea is widely consumed, suffer from the problem.
"Since it is an autoimmune disease, Sjogren's Syndrome causes the body to attack itself and produce extra antibodies that mistakenly target the salivary and lacrimal glands," he says.
New method predicts hip joint decay from chemotherapy
St. Jude study shows that the extent of hip decay is key to predicting which survivors of leukemia/lymphoma who develop osteonecrosis of the femoral head will suffer hip joint collapse requiring surgical repair
Investigators at St. Jude Children's Research Hospital say they have found the best way for predicting when patients will need future surgery to repair hip joints that have deteriorated because of pediatric leukemia or lymphoma treatment.
The investigators found that if more than 30 percent of the head of the bone fitting into the hip socket is deteriorated, it is at high risk of collapsing and requiring reconstructive surgery within two years.
The study is significant because the intensive use of corticosteroid drugs that have been implicated in development of osteonecrosis, or bone deterioration, is a major component of chemotherapy for pediatric leukemia and lymphoma. The drugs have been key to raising the survival rates of children with these cancers, and currently there is no adequate substitute for their use. Therefore, it is important for clinicians to monitor patients during treatment and identify those at highest risk for this complication. Eventually, genetic or other tests may be developed to help predict these patients. This is a subject of ongoing study.
A report on this work appears in the April 20 issue of "Journal of Clinical Oncology."
Hip collapse occurs following deterioration of the ball-like top part of the upper leg bone, or femur, which fits into the hip socket. Degeneration of this area, called osteonecrosis of the capital femoral epiphysis, is a common problem among children undergoing chemotherapy for leukemia or lymphoma.
"Being able to predict which children are likely to experience serious bone deterioration in the future will help investigators identify and monitor survivors who are at particularly high risk for developing this problem," said Sue Kaste, D.O., a member of the Radiological Sciences department at St. Jude. Kaste is the paper's senior author.
Investigators at St. Jude Children's Research Hospital say they have found the best way for predicting when patients will need future surgery to repair hip joints that have deteriorated because of pediatric leukemia or lymphoma treatment.
The investigators found that if more than 30 percent of the head of the bone fitting into the hip socket is deteriorated, it is at high risk of collapsing and requiring reconstructive surgery within two years.
The study is significant because the intensive use of corticosteroid drugs that have been implicated in development of osteonecrosis, or bone deterioration, is a major component of chemotherapy for pediatric leukemia and lymphoma. The drugs have been key to raising the survival rates of children with these cancers, and currently there is no adequate substitute for their use. Therefore, it is important for clinicians to monitor patients during treatment and identify those at highest risk for this complication. Eventually, genetic or other tests may be developed to help predict these patients. This is a subject of ongoing study.
A report on this work appears in the April 20 issue of "Journal of Clinical Oncology."
Hip collapse occurs following deterioration of the ball-like top part of the upper leg bone, or femur, which fits into the hip socket. Degeneration of this area, called osteonecrosis of the capital femoral epiphysis, is a common problem among children undergoing chemotherapy for leukemia or lymphoma.
"Being able to predict which children are likely to experience serious bone deterioration in the future will help investigators identify and monitor survivors who are at particularly high risk for developing this problem," said Sue Kaste, D.O., a member of the Radiological Sciences department at St. Jude. Kaste is the paper's senior author.
Thursday, April 19, 2007
Cancer stresses partners as well as survivors
Wed Apr 18, 2007 1:27PM EDT
NEW YORK (Reuters Health) - The spouses and partners of cancer survivors experience emotional stress comparable to that seen in the patients themselves, and the long-term social costs may actually be greater, new research suggests.
"These findings highlight the importance of addressing the needs of family members who care for cancer patients, and who may be suffering in silence," lead author Dr. Michelle M. Bishop, from the University of Florida in Gainesville, said in a statement. "We need to acknowledge that cancer occurs in the context of a family that is profoundly affected by the experience, and that needs intervention for their own well-being."
The findings, which appear in the Journal of Clinical Oncology, are based on a study of 177 survivor-partner pairs and 133 partner pairs unaffected by cancer. All of the cancer survivors had undergone stem cell transplants. Emotional and physical health was assessed using standard measures an average of 6.7 years after transplantation.
As anticipated, physical health was better in the partners of the cancer survivors, and it was similar to that reported by the control subjects, the findings indicate.
Cancer survivors also had worse mental functioning than their partners and the control subjects. However, partners of the survivors had worse mental functioning compared with the control subjects. The same pattern was seen for levels of fatigue, often a sign of depression. Depressive symptoms, sleep problems and sexual difficulties were also more common in partners of cancer survivors than in the control subjects.
Depression was more likely to be addressed in survivors than in their partners, the authors note. Moreover, compared with the cancer survivors and controls, partners of survivors reported they had less social support, lower levels of spiritual well-being, and greater loneliness. Partners of survivors also experienced little psychological benefit or "post-traumatic growth" for having overcome a stressful experience.
NEW YORK (Reuters Health) - The spouses and partners of cancer survivors experience emotional stress comparable to that seen in the patients themselves, and the long-term social costs may actually be greater, new research suggests.
"These findings highlight the importance of addressing the needs of family members who care for cancer patients, and who may be suffering in silence," lead author Dr. Michelle M. Bishop, from the University of Florida in Gainesville, said in a statement. "We need to acknowledge that cancer occurs in the context of a family that is profoundly affected by the experience, and that needs intervention for their own well-being."
The findings, which appear in the Journal of Clinical Oncology, are based on a study of 177 survivor-partner pairs and 133 partner pairs unaffected by cancer. All of the cancer survivors had undergone stem cell transplants. Emotional and physical health was assessed using standard measures an average of 6.7 years after transplantation.
As anticipated, physical health was better in the partners of the cancer survivors, and it was similar to that reported by the control subjects, the findings indicate.
Cancer survivors also had worse mental functioning than their partners and the control subjects. However, partners of the survivors had worse mental functioning compared with the control subjects. The same pattern was seen for levels of fatigue, often a sign of depression. Depressive symptoms, sleep problems and sexual difficulties were also more common in partners of cancer survivors than in the control subjects.
Depression was more likely to be addressed in survivors than in their partners, the authors note. Moreover, compared with the cancer survivors and controls, partners of survivors reported they had less social support, lower levels of spiritual well-being, and greater loneliness. Partners of survivors also experienced little psychological benefit or "post-traumatic growth" for having overcome a stressful experience.
Flu triggers heart attacks, study shows
Wed Apr 18, 2007 2:07PM EDT
WASHINGTON (Reuters) - Influenza can trigger deadly heart attacks, researchers said on Wednesday in a study that supports what experts have long believed -- flu can kill people even if they do not die directly from the flu.
Their report shows that the seasonal virus can worsen heart disease and that deaths from heart attacks and heart disease are far more common during flu season.
This can add up to 90,000 extra deaths a year in the United States alone, said Dr. Mohammad Madjid of the University of Texas-Houston, who led the study.
Writing in the European Heart Journal, the researchers said their findings add to a growing list of reasons why people should get annual flu shots. They also said people with heart disease should stick to their medications religiously.
"Our research has shown that influenza epidemics are associated with a rise in coronary deaths," Madjid said in a statement. "This calls for more intensive efforts to increase the vaccination rate in people at risk of coronary heart disease.
"This may be especially important in an influenza pandemic when we would expect to see high mortality among the elderly and those suffering from heart problems or who have multiple coronary risk factors," he said.
WASHINGTON (Reuters) - Influenza can trigger deadly heart attacks, researchers said on Wednesday in a study that supports what experts have long believed -- flu can kill people even if they do not die directly from the flu.
Their report shows that the seasonal virus can worsen heart disease and that deaths from heart attacks and heart disease are far more common during flu season.
This can add up to 90,000 extra deaths a year in the United States alone, said Dr. Mohammad Madjid of the University of Texas-Houston, who led the study.
Writing in the European Heart Journal, the researchers said their findings add to a growing list of reasons why people should get annual flu shots. They also said people with heart disease should stick to their medications religiously.
"Our research has shown that influenza epidemics are associated with a rise in coronary deaths," Madjid said in a statement. "This calls for more intensive efforts to increase the vaccination rate in people at risk of coronary heart disease.
"This may be especially important in an influenza pandemic when we would expect to see high mortality among the elderly and those suffering from heart problems or who have multiple coronary risk factors," he said.
Oral Lichen Planus Responds to Methotrexate, Pimecrolimus
April 18, 2007 — Oral lichen planus (OLP) and oral erosive lichen planus (OELP) may respond to methotrexate or pimecrolimus, respectively, according to the results of 2 studies reported in the April issue of the Archives of Dermatology. For OLP, a laddered therapeutic approach is effective; for OELP, 1% pimecrolimus cream is effective and well tolerated but requires long-term application.
"Oral lichen planus (OLP) is a chronic inflammatory disorder that can cause local irritation and discomfort with attendant poor dentition and nutrition," write Dorothea C. Torti, BA, from Wake Forest University Health Sciences in Winston Salem, North Carolina, and colleagues. "Although a range of therapeutic options is available, data on the long-term efficacy of treatments for this chronic disease are limited. To identify agents that might be effective in OLP treatment over a longer term, and to explore their sequential use in treatment-refractory patients, we studied patients who received multiple OLP therapies and who were followed up for an average of more than 2 years."
Torti and colleagues performed a retrospective medical record review of 50 treatment-refractory patients (35 women; age range, 41 - 80 years) with histologically confirmed, erosive OLP seen in a university dermatology clinic between January 1, 1997, and December 31, 2005.
"Oral lichen planus (OLP) is a chronic inflammatory disorder that can cause local irritation and discomfort with attendant poor dentition and nutrition," write Dorothea C. Torti, BA, from Wake Forest University Health Sciences in Winston Salem, North Carolina, and colleagues. "Although a range of therapeutic options is available, data on the long-term efficacy of treatments for this chronic disease are limited. To identify agents that might be effective in OLP treatment over a longer term, and to explore their sequential use in treatment-refractory patients, we studied patients who received multiple OLP therapies and who were followed up for an average of more than 2 years."
Torti and colleagues performed a retrospective medical record review of 50 treatment-refractory patients (35 women; age range, 41 - 80 years) with histologically confirmed, erosive OLP seen in a university dermatology clinic between January 1, 1997, and December 31, 2005.
Screening for Aortic Aneurysms in Older Men Decreases Mortality
April 18, 2007 — Ultrasound screening for aortic aneurysms in men, but not in women, aged 65 to 79 years is effective in decreasing mortality, according to the results of a review published in the April 18 issue of the Cochrane Database of Systematic Reviews.
Abdominal aortic aneurysm (AAA) is found in 5% to 10% of men aged 65 to 79 years, with the major complication being rupture that presents as a surgical emergency.
"The mortality after rupture is high, 80% for patients reaching hospital and 50% for those undergoing surgery for emergency repair," write P.A. Cosford and G.C. Leng, from the Cochrane Collaboration. "Currently elective surgical repair is recommended for aneurysms discovered to be larger than 5.5 cm to prevent rupture. There is interest in population screening to detect, monitor and repair abdominal aortic aneurysms before rupture."
To determine the effects of screening asymptomatic individuals for AAA on mortality, subsequent treatment, quality of life, and cost effectiveness of screening, the Cochrane Peripheral Vascular Diseases Group searched their Trials Register through January 26, 2007, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library through Issue 1, 2007.
Two authors independently evaluated randomized controlled trials of population screening for AAA and extracted data from 4 studies enrolling 127,891 men and 9342 women. Two of the studies were conducted in the United Kingdom, 1 in Denmark, and 1 in Australia. Only 1 trial included women; results for men and women were analyzed separately.
Abdominal aortic aneurysm (AAA) is found in 5% to 10% of men aged 65 to 79 years, with the major complication being rupture that presents as a surgical emergency.
"The mortality after rupture is high, 80% for patients reaching hospital and 50% for those undergoing surgery for emergency repair," write P.A. Cosford and G.C. Leng, from the Cochrane Collaboration. "Currently elective surgical repair is recommended for aneurysms discovered to be larger than 5.5 cm to prevent rupture. There is interest in population screening to detect, monitor and repair abdominal aortic aneurysms before rupture."
To determine the effects of screening asymptomatic individuals for AAA on mortality, subsequent treatment, quality of life, and cost effectiveness of screening, the Cochrane Peripheral Vascular Diseases Group searched their Trials Register through January 26, 2007, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library through Issue 1, 2007.
Two authors independently evaluated randomized controlled trials of population screening for AAA and extracted data from 4 studies enrolling 127,891 men and 9342 women. Two of the studies were conducted in the United Kingdom, 1 in Denmark, and 1 in Australia. Only 1 trial included women; results for men and women were analyzed separately.
Dermatologists Superior to Other Physicians at Flagging Early Melanoma
ATLANTA, April 18 -- When melanomas are diagnosed by a dermatologist, patients are likelier to have early-stage disease and longer survival than those whose lesion was diagnosed by a non-dermatologist, researchers reported.Patients diagnosed by a dermatologist had a preponderance of thin melanoma at stages zero, or I or II, with higher survival rates at two and five years than those diagnosed by a non-dermatologist, Suephy C. Chen, M.D., of Emory University here, and colleagues reported in the April 16 issue of the Archives of Dermatology.
Melanoma is the fifth most common malignancy for men and the sixth most common for women, with a sharp increase since the 1930s. Patients diagnosed early have a 90% cure rate, compared with five-year survival rates of less than 20% for metastatic disease, the researchers wrote.
Non-dermatologists included family practitioners, internists, ob-gyns, plastic surgeons, and oncologists.
The data emerged from a retrospective analysis using Medicare claims (codes for different kinds of physician visits), and the National Cancer Institute's SEER database (cancer diagnoses and outcomes) from 1991 to 1996. The registries came from 12 U.S. sites. However, those diagnosed by a dermatologist were more likely to live in an urban area.
Of 2,020 participants in the study sample, 1,467 (73%) were diagnosed by a dermatologist and 553 (27%) were diagnosed by a non-dermatologist. Tumor detection by a dermatologist versus a non-dermatologist was associated with an earlier stage melanoma (stage 0, stage I, and stage II versus stage III and stage IV; x2 test, P<0.01) and a thinner tumor (Breslow thickness, 0.86 mm vs. 1.00 mm; P<0.05).
Melanoma is the fifth most common malignancy for men and the sixth most common for women, with a sharp increase since the 1930s. Patients diagnosed early have a 90% cure rate, compared with five-year survival rates of less than 20% for metastatic disease, the researchers wrote.
Non-dermatologists included family practitioners, internists, ob-gyns, plastic surgeons, and oncologists.
The data emerged from a retrospective analysis using Medicare claims (codes for different kinds of physician visits), and the National Cancer Institute's SEER database (cancer diagnoses and outcomes) from 1991 to 1996. The registries came from 12 U.S. sites. However, those diagnosed by a dermatologist were more likely to live in an urban area.
Of 2,020 participants in the study sample, 1,467 (73%) were diagnosed by a dermatologist and 553 (27%) were diagnosed by a non-dermatologist. Tumor detection by a dermatologist versus a non-dermatologist was associated with an earlier stage melanoma (stage 0, stage I, and stage II versus stage III and stage IV; x2 test, P<0.01) and a thinner tumor (Breslow thickness, 0.86 mm vs. 1.00 mm; P<0.05).
Anemia After Kidney Transplant Worsens Outcomes
TORONTO, April 18 -- Anemia after kidney transplantation nearly doubles mortality and graft failure risk over four years, according to international researchers.
Among 938 Hungarian kidney transplant patients, anemia raised the mortality risk 69% and graft failure risk 2.5-fold, reported Istvan Mucsi, M.D., of the University of Toronto and Semmelweis University in Budapest, and colleagues, in the April issue of the American Journal of Transplantation.
The results suggested that post-renal transplant anemia should be treated according to National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for chronic kidney disease-related anemia, Dr. Mucsi said.
However, the treatment of anemia as a complication of chronic kidney disease is itself undergoing changes that suggest caution in use of erythropoiesis-stimulating agents, said Matthew R. Weir, M.D., of the University of Maryland in Baltimore, in an accompanying editorial.
Last month, the FDA issued a black box warning for erythropoiesis-stimulating agents, including darbepoetin alfa (Aranesp) and epoetin alfa (Epogen, Procrit), that pointed out aggressively raising hemoglobin to a target of 12 g/dL or higher was associated with "serious and life-threatening side-effects and/or death."
Two of the studies that sparked the warning -- CREATE and CHOIR -- were testing higher hemoglobin targets for chronic kidney disease patients not on dialysis.
Among 938 Hungarian kidney transplant patients, anemia raised the mortality risk 69% and graft failure risk 2.5-fold, reported Istvan Mucsi, M.D., of the University of Toronto and Semmelweis University in Budapest, and colleagues, in the April issue of the American Journal of Transplantation.
The results suggested that post-renal transplant anemia should be treated according to National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for chronic kidney disease-related anemia, Dr. Mucsi said.
However, the treatment of anemia as a complication of chronic kidney disease is itself undergoing changes that suggest caution in use of erythropoiesis-stimulating agents, said Matthew R. Weir, M.D., of the University of Maryland in Baltimore, in an accompanying editorial.
Last month, the FDA issued a black box warning for erythropoiesis-stimulating agents, including darbepoetin alfa (Aranesp) and epoetin alfa (Epogen, Procrit), that pointed out aggressively raising hemoglobin to a target of 12 g/dL or higher was associated with "serious and life-threatening side-effects and/or death."
Two of the studies that sparked the warning -- CREATE and CHOIR -- were testing higher hemoglobin targets for chronic kidney disease patients not on dialysis.
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