AIDS Patients Face Downside of Living Longer
By JANE GROSS
CHICAGO — John Holloway received a diagnosis of AIDS nearly two decades ago, when the disease was a speedy death sentence and treatment a distant dream.
Yet at 59 he is alive, thanks to a cocktail of drugs that changed the course of an epidemic. But with longevity has come a host of unexpected medical conditions, which challenge the prevailing view of AIDS as a manageable, chronic disease.
Mr. Holloway, who lives in a housing complex designed for the frail elderly, suffers from complex health problems usually associated with advanced age: chronic obstructive pulmonary disease, diabetes, kidney failure, a bleeding ulcer, severe depression, rectal cancer and the lingering effects of a broken hip.
Those illnesses, more severe than his 84-year-old father’s, are not what Mr. Holloway expected when lifesaving antiretroviral drugs became the standard of care in the mid-1990s.
The drugs gave Mr. Holloway back his future.
But at what cost?
That is the question, heretical to some, that is now being voiced by scientists, doctors and patients encountering a constellation of ailments showing up prematurely or in disproportionate numbers among the first wave of AIDS survivors to reach late middle age.
There have been only small, inconclusive studies on the causes of aging-related health problems among AIDS patients.
Without definitive research, which has just begun, that second wave of suffering could be a coincidence, although it is hard to find anyone who thinks so.
Instead, experts are coming to believe that the immune system and organs of long-term survivors took an irreversible beating before the advent of lifesaving drugs and that those very drugs then produced additional complications because of their toxicity — a one-two punch.
“The sum total of illnesses can become overwhelming,” said Charles A. Emlet, an associate professor at the University of Washington at Tacoma and a leading H.I.V. and aging researcher, who sees new collaborations between specialists that will improve care.
“AIDS is a very serious disease, but longtime survivors have come to grips with it,” Dr. Emlet continued, explaining that while some patients experienced unpleasant side effects from the antiretrovirals, a vast majority found a cocktail they could tolerate. “Then all of a sudden they are bombarded with a whole new round of insults, which complicate their medical regime and have the potential of being life threatening. That undermines their sense of stability and makes it much more difficult to adjust.”
The graying of the AIDS epidemic has increased interest in the connection between AIDS and cardiovascular disease, certain cancers, diabetes, osteoporosis and depression. The number of people 50 and older living with H.I.V., the virus that causes AIDS, has increased 77 percent from 2001 to 2005, according to the federal Centers for Disease Control, and they now represent more than a quarter of all cases in the United States.
The most comprehensive research has come from the AIDS Community Research Initiative of America, which has studied 1,000 long-term survivors in New York City, and the Multi-Site AIDS Cohort Study, financed by the National Institutes of Health, which has followed 2,000 subjects nationwide for the past 25 years.
The Acria study, published in 2006, examined psychological, not medical, issues and found unusual rates of depression and isolation among older people with AIDS.
The Multi-Site AIDS Cohort Study, or MACS, will directly examine the intersection of AIDS and aging over the next five years. Dr. John Phair, a principal investigator for the study, which has health data from both infected and uninfected men, said “prolonged survival” coupled with the “naturally occurring health issues” of old age raised pressing research questions: “Which health issues are a direct result of aging, which are a direct result of H.I.V. and what role do H.I.V. meds play?”
The MACS investigators, and other researchers, defend the slow pace of research as a function of numbers. The first generation of AIDS patients, in the mid-1980s, had no effective treatments for a decade, and died in overwhelming numbers, leaving few survivors to study.
Those survivors, like Mr. Holloway, gaunt from chemotherapy and radiation and mostly housebound, lurch from crisis to crisis. Mr. Holloway says his adjustment strategy is simple: “Deal with it.” Still he notes, ruefully, that his father has no medical complaints other than arthritis, failing eyesight and slight hearing loss.
“I look at how gracefully he’s aged, and I wish I understood what was happening to my body,” Mr. Holloway said during a recent home visit from his case manager at the Howard Brown Health Center here, a gay, lesbian and transgender organization. The case manager, Lisa Katona, could soothe but not inform him. “Nobody’s sure what causes what,” Ms. Katona told Mr. Holloway. “You folks are the first to go through this and we’re learning as we go.”
Mr. Holloway is uncomplaining even in the face of pneumonia and a 40-pound weight loss, both associated with his cancer treatment. Has the cost been too high? He says it has not, “considering the alternatives.”
Halfway across the country, Jeff, 56-year-old New Yorker who was found to have AIDS in 1987, said he asks himself that question often.
Jeff, who asked that he not be fully identified, has had one hip replacement because of a condition called avascular necrosis, the death of cells from inadequate blood supply, and needs another to avoid a wheelchair. Many experts think that avascular necrosis is caused by the steroids many early AIDS sufferers took for pneumonia.
“The virus is under control, and I should be in a state of ecstasy,” he said, “but I can’t even tie my own shoe laces and get up and down the subway stairs. ”
His bones are spongy from osteoporosis, a disorder that afflicts many postmenopausal women but rarely middle-aged men, except some with AIDS. No research has explained the unusual incidence.
In addition, Jeff has Parkinson’s disease, which is causing tremors and memory lapses.
He is in an AIDS support group at SAGE, a social service agency for older gay men and lesbians. His fellow group members also say they find the illnesses associated with age more taxing than the H.I.V. infection. One 69-year-old member of the group, for example, has had several heart attacks and triple bypass surgery, and his doctor predicts that heart disease is more likely to kill him than AIDS.
Cardiovascular disease and diabetes are associated with a condition called lipodystrophy, which redistributes fat, leaving the face and lower extremities wasted, the belly distended and the back humped. In addition, lipodystrophy raises cholesterol levels and causes glucose intolerance, which is especially dangerous to black people, who are already predisposed to heart disease and diabetes.
At Rivington House, a residence for AIDS patients on the Lower East Side of Manhattan, Dr. Sheree Starrett, the medical director, said that neither heart disease nor diabetes was “terribly hard to treat, except that every time you add more meds there is more chance of something else going wrong.”
Statins, for instance, which are the drug of choice for high cholesterol, are bad for people with abnormal liver function, also a greater risk among blacks. Many AIDS patients have end-stage liver disease, either from intravenous drug use or alcohol abuse. Among Dr. Starrett’s AIDS patients is 58-year-old Dominga Montanez, whose first husband died of AIDS and whose second husband is also infected.
“My liver is acting up, my diabetes is out of control and I fractured my spine” because of osteoporosis, Ms. Montanez said. “To me, the new things are worse than the AIDS.”
There are no data that compare the incidence, age of onset and cause of geriatric diseases in the general population with the long-term survivors of H.I.V. infection. But physicians and researchers say that they do not see people in their mid-50s, absent AIDS, with hip replacements associated with vascular necrosis, heart disease or diabetes related to lipodystrophy, or osteoporosis without the usual risk factors.
“All we can do right now is make inferences from thing to thing to thing,” said Dr. Tom Barrett, medical director of Howard Brown. “They might have gotten some of these diseases anyway. But the rates and the timing, and the association with certain drugs, makes everyone feel this is a different problem.”
One theory about why research on AIDS and aging has barely begun is “the rapid increase in numbers,” Dr. Emlet said. The federal disease centers’ most recent surveillance data, from 33 states that meet certain reporting criteria, showed that the number of people 50 and older with AIDS or H.I.V. infection was 115,871 in 2005, nearly double the 64,445 in 2001.
Another is the routine exclusion of older people from drug trials by big pharmaceutical companies. The studies are designed to measure safety and efficacy but generally not long-term side effects.
Those explanations do not satisfy Larry Kramer, founder of several AIDS advocacy groups. Mr. Kramer, 73 and a long-term survivor, said he had always suspected “it was only a matter of time before stuff like this happened” given the potency of the antiretroviral drugs. “How long will the human body be able to tolerate that constant bombardment?” he asked. “Well, we are now seeing that many bodies can’t. Once again, just as we thought we were out of the woods, sort of, we have good reason again to be really scared.”
The lack of research also limits a patient’s care. Dr. Barrett says the incidence of osteoporosis warrants routine screening. Medicare, Medicaid and private insurers, however, will not cover bone density tests for middle-aged men.
Marty Weinstein, 55 and infected since 1982, has had a pacemaker installed, has been found to have osteoporosis, and has been treated for anal cancer and medicated for severe depression — all in the last year. He also has cognitive deficits.
A former professor of psychology in Chicago, he presses his doctors about cause and effect. Sometimes they offer a hypothesis, he said, but never a certain explanation.
“I know the first concern was keeping us alive,” Mr. Weinstein said. “But now that so many people are going to live longer lives, how are we going to get them through this emotionally and physically?”
Monday, January 07, 2008
Localized Breast Cancer Cells Have Potential to Spread
Early breast cancer tumors that have not yet spread contain cells with a predisposition to migrate to new tissue, a new study finds.
So, just because a cancer has not yet spread doesn't mean its cells lack the ability or inclination to do so, warned researchers at the Salk Institute for Biological Studies in La Jolla, Calif. They added that there is also no evidence to suggest that these cells correlate with a positive or negative health outcome for women with breast cancer.
"This is an exciting finding, because it suggests that cells might acquire migratory properties much earlier than expected," senior author Tony Hunter, a professor in the Molecular and Cell Biology Laboratory at the institute, said in a prepared statement.
Self-screening for breast cancer, regular doctor's visits and mammograms have all made it possible to identify breast cancer tumors in their early stages. When identified early, the cancer cells usually are within the confines of a milk duct, the most common origin of breast cancer tumors.
Removal of the small tumor and surrounding tissue, called a lumpectomy, is the standard treatment for this early stage of breast cancer. The question of whether women should also have radiation treatment to address any stray cancer cells has been hotly debated, partly because approximately 16 percent of these patients will see their cancer return within five years.
According to the researchers, the identification of cells that could spread, called motile cells, supports the need for radiation, which is usually determined by tumor size.
The research team studied breast cancer in the lab by allowing breast tissue to grow under observation. The researchers also turned on a series of chemical signals, called the ERK1/2 MAP kinase pathway, that is often active during tumor growth. They then watched as breast cancer cells began to grow and become more aggressive.
The lab setting limited the spreading of the cancer cells, but the researchers interpreted the activity of the cells to indicate a potential for spread.
Writing in the current edition of The Journal of Cell Biology, the researchers said the next step is to identify biological markers to help oncologists diagnose patients who are at higher risk of metastasis.
Early breast cancer tumors that have not yet spread contain cells with a predisposition to migrate to new tissue, a new study finds.
So, just because a cancer has not yet spread doesn't mean its cells lack the ability or inclination to do so, warned researchers at the Salk Institute for Biological Studies in La Jolla, Calif. They added that there is also no evidence to suggest that these cells correlate with a positive or negative health outcome for women with breast cancer.
"This is an exciting finding, because it suggests that cells might acquire migratory properties much earlier than expected," senior author Tony Hunter, a professor in the Molecular and Cell Biology Laboratory at the institute, said in a prepared statement.
Self-screening for breast cancer, regular doctor's visits and mammograms have all made it possible to identify breast cancer tumors in their early stages. When identified early, the cancer cells usually are within the confines of a milk duct, the most common origin of breast cancer tumors.
Removal of the small tumor and surrounding tissue, called a lumpectomy, is the standard treatment for this early stage of breast cancer. The question of whether women should also have radiation treatment to address any stray cancer cells has been hotly debated, partly because approximately 16 percent of these patients will see their cancer return within five years.
According to the researchers, the identification of cells that could spread, called motile cells, supports the need for radiation, which is usually determined by tumor size.
The research team studied breast cancer in the lab by allowing breast tissue to grow under observation. The researchers also turned on a series of chemical signals, called the ERK1/2 MAP kinase pathway, that is often active during tumor growth. They then watched as breast cancer cells began to grow and become more aggressive.
The lab setting limited the spreading of the cancer cells, but the researchers interpreted the activity of the cells to indicate a potential for spread.
Writing in the current edition of The Journal of Cell Biology, the researchers said the next step is to identify biological markers to help oncologists diagnose patients who are at higher risk of metastasis.
Fatherhood Tied to Higher Prostate Cancer Risk
Men who father children may be at higher risk of prostate cancer compared to those who forego the life experience, a Danish study suggests.
The large-scale study looked at all men born in Denmark between 1935 and 1988. It found that childless men had a 17 percent lower incidence of prostate cancer than fathers did.
The reasons why remain unclear.
"It is not possible from the current data to point out what factors associated with childlessness, whether biologic, environmental, social or behavioral, were responsible for the observed reduction in prostate cancer risk," wrote researchers at the Statens Serum Institut, in Copenhagen.
The study is published in the Jan. 7 online edition of Cancer, and will appear in the journal's Feb. 15 print edition.
The findings echo those of a prior Scandinavian study, published in 2005, which looked at more than 48,800 cases of prostate cancer. That report also found a 17 percent lower incidence of prostate cancer among childless men.
In neither of the two studies did the gender of the children fathered affect the man's risk of prostate cancer. However, one large-scale study conducted several years ago in Israel found that the malignancy was 40 percent more common among men with no sons.
Dr. Susan Harlap, now a professor of epidemiology at New York University, led that Israeli study. She said the differing results reflect the complex factors, genetic and otherwise, that underlie prostate cancer risk throughout the world.
"The incidence of prostate cancer is different in Israeli Jews than in northwestern Europeans," Harlap said. "It may be a different disease, and there may be a different set of causes. We do know there are genetic causes of prostate cancer, and there could be different sets of genes in Israeli Jews than in northwestern Europeans."
A relationship between prostate cancer risk and having no sons would point to a mutation in the Y chromosome, which determines the male sex of a child. But there are complexities to such a relationship, Harlap noted.
"If the effect is due to Y chromosomes, they are quite specific to ethnic groups," she said. "Israeli Jews are different from Danes and Swedes."
The complexity of the issue is also illustrated by the different findings of the two Scandinavian studies about fatherhood and risk. The new Danish report finds that "among fathers, a significant trend was observed of gradually reduced prostate cancer with increasing number of children" -- in other words, fatherhood was linked to an increased risk for prostate cancer, but fathering more children begins to bring that risk down again. In contrast, the earlier study found "no further change in risk associated with fathering of more than two children."
Dr. Otis Brawley, chief medical officer of the American Cancer Society, was less than impressed by the Copenhagen findings, however. Despite the large numbers, the result was "just barely statistically significant," Brawley said, and could be the result of pure chance.
In a study of this kind, he said, "you occasionally get something that is statistically significant but is not really significant biologically."
In any case, men shouldn't make decisions on fatherhood based on the study results, Brawley stressed. "I would never suggest to men that their wives not get pregnant so they don't get prostate cancer," he said. "Lack of fatherhood is not a strong preventive of prostate cancer."
Any relationship that does exist is probably very weak, Brawley said. "If there is a real correlation, I would like to know what the true cause is," he said. "I suspect we will never know."
More information
There's more on prostate cancer at the American Cancer Society.
Men who father children may be at higher risk of prostate cancer compared to those who forego the life experience, a Danish study suggests.
The large-scale study looked at all men born in Denmark between 1935 and 1988. It found that childless men had a 17 percent lower incidence of prostate cancer than fathers did.
The reasons why remain unclear.
"It is not possible from the current data to point out what factors associated with childlessness, whether biologic, environmental, social or behavioral, were responsible for the observed reduction in prostate cancer risk," wrote researchers at the Statens Serum Institut, in Copenhagen.
The study is published in the Jan. 7 online edition of Cancer, and will appear in the journal's Feb. 15 print edition.
The findings echo those of a prior Scandinavian study, published in 2005, which looked at more than 48,800 cases of prostate cancer. That report also found a 17 percent lower incidence of prostate cancer among childless men.
In neither of the two studies did the gender of the children fathered affect the man's risk of prostate cancer. However, one large-scale study conducted several years ago in Israel found that the malignancy was 40 percent more common among men with no sons.
Dr. Susan Harlap, now a professor of epidemiology at New York University, led that Israeli study. She said the differing results reflect the complex factors, genetic and otherwise, that underlie prostate cancer risk throughout the world.
"The incidence of prostate cancer is different in Israeli Jews than in northwestern Europeans," Harlap said. "It may be a different disease, and there may be a different set of causes. We do know there are genetic causes of prostate cancer, and there could be different sets of genes in Israeli Jews than in northwestern Europeans."
A relationship between prostate cancer risk and having no sons would point to a mutation in the Y chromosome, which determines the male sex of a child. But there are complexities to such a relationship, Harlap noted.
"If the effect is due to Y chromosomes, they are quite specific to ethnic groups," she said. "Israeli Jews are different from Danes and Swedes."
The complexity of the issue is also illustrated by the different findings of the two Scandinavian studies about fatherhood and risk. The new Danish report finds that "among fathers, a significant trend was observed of gradually reduced prostate cancer with increasing number of children" -- in other words, fatherhood was linked to an increased risk for prostate cancer, but fathering more children begins to bring that risk down again. In contrast, the earlier study found "no further change in risk associated with fathering of more than two children."
Dr. Otis Brawley, chief medical officer of the American Cancer Society, was less than impressed by the Copenhagen findings, however. Despite the large numbers, the result was "just barely statistically significant," Brawley said, and could be the result of pure chance.
In a study of this kind, he said, "you occasionally get something that is statistically significant but is not really significant biologically."
In any case, men shouldn't make decisions on fatherhood based on the study results, Brawley stressed. "I would never suggest to men that their wives not get pregnant so they don't get prostate cancer," he said. "Lack of fatherhood is not a strong preventive of prostate cancer."
Any relationship that does exist is probably very weak, Brawley said. "If there is a real correlation, I would like to know what the true cause is," he said. "I suspect we will never know."
More information
There's more on prostate cancer at the American Cancer Society.
Friday, January 04, 2008
Hospital Strategies to Prevent UTI Found Wanting
By Michael Smith
Sanjay Saint, M.D., MPH, Department of Internal MedicineVA Ann Arbor Healthcare SystemSource: University of Michigan Health System
ANN ARBOR, Mich., Jan. 3 -- Fewer than half of U.S. hospitals track which patients have an indwelling urinary catheter and only about a quarter have a system that monitors how long a catheter has been in place, a new survey shows. And fewer than one hospital in 10 employs a system that has been shown to reduce infections -- a daily reminder that asks physicians if a patient's catheter is still needed, Sanjay Saint, M.D., of the University of Michigan here, and colleagues, reported in the January issue of Clinical Infectious Diseases.
Infections related to urinary catheters are a "common and costly patient-safety problem," Dr. Saint said, and until this survey of 719 hospitals there was little information on how hospitals were dealing with the issue.
"Now that we have these data," Dr. Saint said, "it's clear that there's no one dominant practice that's being used, including physician reminders, which have proven benefit and make a lot of common sense."
Dr. Saint and colleagues surveyed all 119 Veterans Affairs hospitals that have an acute care department, as well as 600 non-VA hospitals across the country. The response rate was 72%.
The survey found that:
30% of hospitals regularly use antimicrobial urinary catheters and portable bladder scanners.
14% regularly use condom catheters in men.
9% regularly use catheter reminders and suprapubic catheters.
3% regularly use antimicrobial agents in the drainage bag.
Interestingly, there were significant differences between VA and non-VA hospitals. The VA hospitals were more likely to use portable bladder scanners (49% versus 29%), condom catheters in men (46% versus 12%), and suprapubic catheters (22% versus 9%), all significant at P<0.001.
On the other hand, non-VA hospitals were significantly more likely to use antimicrobial urinary catheters -- at 30% versus 14%, which was significant at P<0.002.
The VA hospitals were included in the survey to see if there were any effects of a centralized, top-down structure, Dr. Saint and colleagues said.
"Centralization does seem to be relevant in terms of the use of infection prevention practices, but not in a straightforward manner," they concluded, because four of five infection control practices were more common in VA hospitals.
On the other hand, there was little difference between VA and other hospitals when it came to one of the most effective practices -- physician reminders and/or a default stop order.
Only 11.5% of VA hospitals routinely remind doctors to re-think the need for a catheter or use a stop order as the default practice, compared with 9.2% of non-VA institutions, the survey found.
In the absence of such a routine, Dr. Saint offered this advice: "The bottom line for hospitalized patients and their families is, if you have a catheter, ask the doctor or nurse every day if you really still need it."
Nosocomial urinary tract infections are surprisingly neglected, considering their status as "the single most common hospital-acquired infection," according to Lindsay Nicolle, M.D., of the University of Manitoba in Winnipeg.
In an accompanying editorial, Dr. Nicolle said that about 40% of all hospital-acquired infections are in the urinary tract, and 80% of those result from indwelling catheters.
Yet, Dr. Nicolle said, the results obtained by Dr. Saint and colleagues suggests that hospitals "are not paying attention" to the issue, or were not in 2005, when the survey was conducted.
Dr. Nicolle noted that implementation of recent patient safety initiatives is making changes, but concluded that "clearly, much progress is needed."
The study was supported by the Department of Veterans Affairs and the Ann Arbor VA Medical Center/University of Michigan Patient Safety Enhancement Program.
Dr. Saint reported honoraria for speaking at a nosocomial infection conference sponsored by VHA, a group-purchasing organization. Dr. Nicolle reported no conflicts.
Primary source: Clinical Infectious DiseasesSource reference:Saint S, et al "Preventing hospital-acquired urinary tract infection in the United States: a national study" Clinical Infectious Diseases 2008; 46: 243-50. Additional source: Clinical Infectious DiseasesSource reference: Nicolle L, "The prevention of hospital-acquired urinary tract infection" Clinical Infectious Diseases 2008; 46: 251-3.
By Michael Smith
Sanjay Saint, M.D., MPH, Department of Internal MedicineVA Ann Arbor Healthcare SystemSource: University of Michigan Health System
ANN ARBOR, Mich., Jan. 3 -- Fewer than half of U.S. hospitals track which patients have an indwelling urinary catheter and only about a quarter have a system that monitors how long a catheter has been in place, a new survey shows. And fewer than one hospital in 10 employs a system that has been shown to reduce infections -- a daily reminder that asks physicians if a patient's catheter is still needed, Sanjay Saint, M.D., of the University of Michigan here, and colleagues, reported in the January issue of Clinical Infectious Diseases.
Infections related to urinary catheters are a "common and costly patient-safety problem," Dr. Saint said, and until this survey of 719 hospitals there was little information on how hospitals were dealing with the issue.
"Now that we have these data," Dr. Saint said, "it's clear that there's no one dominant practice that's being used, including physician reminders, which have proven benefit and make a lot of common sense."
Dr. Saint and colleagues surveyed all 119 Veterans Affairs hospitals that have an acute care department, as well as 600 non-VA hospitals across the country. The response rate was 72%.
The survey found that:
30% of hospitals regularly use antimicrobial urinary catheters and portable bladder scanners.
14% regularly use condom catheters in men.
9% regularly use catheter reminders and suprapubic catheters.
3% regularly use antimicrobial agents in the drainage bag.
Interestingly, there were significant differences between VA and non-VA hospitals. The VA hospitals were more likely to use portable bladder scanners (49% versus 29%), condom catheters in men (46% versus 12%), and suprapubic catheters (22% versus 9%), all significant at P<0.001.
On the other hand, non-VA hospitals were significantly more likely to use antimicrobial urinary catheters -- at 30% versus 14%, which was significant at P<0.002.
The VA hospitals were included in the survey to see if there were any effects of a centralized, top-down structure, Dr. Saint and colleagues said.
"Centralization does seem to be relevant in terms of the use of infection prevention practices, but not in a straightforward manner," they concluded, because four of five infection control practices were more common in VA hospitals.
On the other hand, there was little difference between VA and other hospitals when it came to one of the most effective practices -- physician reminders and/or a default stop order.
Only 11.5% of VA hospitals routinely remind doctors to re-think the need for a catheter or use a stop order as the default practice, compared with 9.2% of non-VA institutions, the survey found.
In the absence of such a routine, Dr. Saint offered this advice: "The bottom line for hospitalized patients and their families is, if you have a catheter, ask the doctor or nurse every day if you really still need it."
Nosocomial urinary tract infections are surprisingly neglected, considering their status as "the single most common hospital-acquired infection," according to Lindsay Nicolle, M.D., of the University of Manitoba in Winnipeg.
In an accompanying editorial, Dr. Nicolle said that about 40% of all hospital-acquired infections are in the urinary tract, and 80% of those result from indwelling catheters.
Yet, Dr. Nicolle said, the results obtained by Dr. Saint and colleagues suggests that hospitals "are not paying attention" to the issue, or were not in 2005, when the survey was conducted.
Dr. Nicolle noted that implementation of recent patient safety initiatives is making changes, but concluded that "clearly, much progress is needed."
The study was supported by the Department of Veterans Affairs and the Ann Arbor VA Medical Center/University of Michigan Patient Safety Enhancement Program.
Dr. Saint reported honoraria for speaking at a nosocomial infection conference sponsored by VHA, a group-purchasing organization. Dr. Nicolle reported no conflicts.
Primary source: Clinical Infectious DiseasesSource reference:Saint S, et al "Preventing hospital-acquired urinary tract infection in the United States: a national study" Clinical Infectious Diseases 2008; 46: 243-50. Additional source: Clinical Infectious DiseasesSource reference: Nicolle L, "The prevention of hospital-acquired urinary tract infection" Clinical Infectious Diseases 2008; 46: 251-3.
Easier Regimen Effective for Advanced Gastroesophageal Cancer
By Judith Groch
LONDON, Jan. 3 -- There seems to be an alternative approach to untreated advanced gastroesophageal cancer that is easier on patients than a standard regimen, with no less efficacy. In a multicenter randomized trial, capecitabine (Xeloda) and oxaliplatin (Eloxatin), as alternatives to the standard infused fluorouracil and cisplatin (Platinol), matched the older regimen, researchers here reported in the Jan. 3 issue of the New England Journal of Medicine.
Capecitabine, an oral fluoropyrimidine, plus oxaliplatin, a platinum compound, was as effective in prolonging overall survival as fluorouracil and cisplatin, found David Cunningham, M.D., of Royal Marsden Hospital National Health Service Foundation here, and colleagues in Britain and Australia.
Triple chemotherapy with epirubicin (Ellence) plus cisplatin and fluorouracil is standard for advanced gastroesophageal cancer. However, fluorouracil must be infused through an ambulatory infusion pump, which impairs quality of life, while cisplatin, which is nephrotoxic, requires IV hydration, the researchers said.
The phase 3 noninferiority trial for overall survival was designed to determine whether infused fluorouracil can be replaced by oral capecitabine and cisplatin by IV oxaliplatin, which can be given by IV in two hours and does not require hydration. Cisplatin lengthens outpatient visits or may require overnight hospital admission, the researchers said.
From June 2000 through May 2005, 1,002 patients were randomly assigned in a two-by-two study to three-drug therapy with epirubicin and cisplatin plus either fluorouracil or capecitabine. A second group received epirubicin and oxaliplatin plus either fluorouracil or capecitabine.
For the capecitabine-fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval: 0.80 to 0.99).
For the oxaliplatin-cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI: 0.80 to 1.10). For all comparisons, P=0.36.
The upper limit of the confidence intervals for both hazard ratios were well below the predefined noninferiority margin of 1.23, thereby showing noninferiority of both capecitabine and oxaliplatin in the two-by-two comparisons, the researchers said.
Median follow-up was 17.1 months. All groups received epirubicin. Median survival times in the four groups -- cisplatin plus either fluorouracil or capecitabine and oxaliplatin plus either fluorouracil or capecitabine were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively.
Survival rates at one year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively, the researchers reported.
In a secondary analysis, overall survival was longer with the oxaliplatin plus capecitabine group than with cisplatin plus fluorouracil group, with a hazard ratio for death of 0.80 in the oxaliplatin plus capecitabine group (95% CI: 0.66 to 0.97, P=0.02).
Progression-free survival and response rates did not differ significantly among the regimens, while the toxic effects of capecitabine and fluorouracil were similar, the researchers reported.
A planned multivariate analysis confirmed the robustness of the noninferiority result for the primary analysis. Performance status, extent of disease, and age were included in the model.
The subsite of the tumor (esophagus, gastroesophageal junction, or stomach) and the results of histologic analysis (adenocarcinoma or squamous-cell carcinoma) did not significantly affect survival. These variables were excluded from the model, the researchers said.
There was a nonsignificant trend toward improved survival in the capecitabine groups as compared with the fluorouracil groups in the intention-to-treat analysis, they reported.
Compared with cisplatin, oxaliplatin was associated with lower rates of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism, but with slightly higher rates of grade 3 or 4 diarrhea and neuropathy.
This study was supported in part by Hoffmann-La Roche, maker of capecitabine, and sanofi-aventis, maker of oxaliplatin, together with the Gastrointestinal Unit Clinical Research Fund of the Royal Marsden Hospital. The study was conducted under the auspices of the National Cancer Research Institute, of Britain, and the Royal Marsden Hospital.
Dr. Cunningham reported receiving consulting and lecture fees and research grants from Hoffmann-La Roche and sanofi-aventis, and serving as an expert witness for Roche.
Primary source: New England Journal of MedicineSource reference:Cunningham D, et al "Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer" N Engl J Med 2008; 358: 36-46.
By Judith Groch
LONDON, Jan. 3 -- There seems to be an alternative approach to untreated advanced gastroesophageal cancer that is easier on patients than a standard regimen, with no less efficacy. In a multicenter randomized trial, capecitabine (Xeloda) and oxaliplatin (Eloxatin), as alternatives to the standard infused fluorouracil and cisplatin (Platinol), matched the older regimen, researchers here reported in the Jan. 3 issue of the New England Journal of Medicine.
Capecitabine, an oral fluoropyrimidine, plus oxaliplatin, a platinum compound, was as effective in prolonging overall survival as fluorouracil and cisplatin, found David Cunningham, M.D., of Royal Marsden Hospital National Health Service Foundation here, and colleagues in Britain and Australia.
Triple chemotherapy with epirubicin (Ellence) plus cisplatin and fluorouracil is standard for advanced gastroesophageal cancer. However, fluorouracil must be infused through an ambulatory infusion pump, which impairs quality of life, while cisplatin, which is nephrotoxic, requires IV hydration, the researchers said.
The phase 3 noninferiority trial for overall survival was designed to determine whether infused fluorouracil can be replaced by oral capecitabine and cisplatin by IV oxaliplatin, which can be given by IV in two hours and does not require hydration. Cisplatin lengthens outpatient visits or may require overnight hospital admission, the researchers said.
From June 2000 through May 2005, 1,002 patients were randomly assigned in a two-by-two study to three-drug therapy with epirubicin and cisplatin plus either fluorouracil or capecitabine. A second group received epirubicin and oxaliplatin plus either fluorouracil or capecitabine.
For the capecitabine-fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval: 0.80 to 0.99).
For the oxaliplatin-cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI: 0.80 to 1.10). For all comparisons, P=0.36.
The upper limit of the confidence intervals for both hazard ratios were well below the predefined noninferiority margin of 1.23, thereby showing noninferiority of both capecitabine and oxaliplatin in the two-by-two comparisons, the researchers said.
Median follow-up was 17.1 months. All groups received epirubicin. Median survival times in the four groups -- cisplatin plus either fluorouracil or capecitabine and oxaliplatin plus either fluorouracil or capecitabine were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively.
Survival rates at one year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively, the researchers reported.
In a secondary analysis, overall survival was longer with the oxaliplatin plus capecitabine group than with cisplatin plus fluorouracil group, with a hazard ratio for death of 0.80 in the oxaliplatin plus capecitabine group (95% CI: 0.66 to 0.97, P=0.02).
Progression-free survival and response rates did not differ significantly among the regimens, while the toxic effects of capecitabine and fluorouracil were similar, the researchers reported.
A planned multivariate analysis confirmed the robustness of the noninferiority result for the primary analysis. Performance status, extent of disease, and age were included in the model.
The subsite of the tumor (esophagus, gastroesophageal junction, or stomach) and the results of histologic analysis (adenocarcinoma or squamous-cell carcinoma) did not significantly affect survival. These variables were excluded from the model, the researchers said.
There was a nonsignificant trend toward improved survival in the capecitabine groups as compared with the fluorouracil groups in the intention-to-treat analysis, they reported.
Compared with cisplatin, oxaliplatin was associated with lower rates of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism, but with slightly higher rates of grade 3 or 4 diarrhea and neuropathy.
This study was supported in part by Hoffmann-La Roche, maker of capecitabine, and sanofi-aventis, maker of oxaliplatin, together with the Gastrointestinal Unit Clinical Research Fund of the Royal Marsden Hospital. The study was conducted under the auspices of the National Cancer Research Institute, of Britain, and the Royal Marsden Hospital.
Dr. Cunningham reported receiving consulting and lecture fees and research grants from Hoffmann-La Roche and sanofi-aventis, and serving as an expert witness for Roche.
Primary source: New England Journal of MedicineSource reference:Cunningham D, et al "Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer" N Engl J Med 2008; 358: 36-46.
Risks of Anemia Drugs in Chemotherapy Patients Are Bolstered
By Peggy Peck
ROCKVILLE, Md., Jan. 3 -- More research has strengthened an association between erythropoiesis-stimulating agents (ESAs) and an increased risk of mortality when the drugs are used for chemotherapy-induced anemia, the FDA said today.
The new data came from two studies of women with breast cancer or advanced cervical cancer, research that had not been included when the FDA ordered a label change two months ago about excess mortality and/or rapid tumor growth with ESAs. This warning was on the basis of six other studies.
In today's statement, the FDA said that "all eight studies show more rapid tumor growth or shortened survival when patients with breast, non-small cell lung, head and neck, lymphoid, or cervical cancers received ESAs compared to patients who did not receive this treatment. In all of these recent studies, ESAs were administered in an attempt to achieve a hemoglobin level of 12 g/dL or greater, although many patients did not reach that level."
The FDA said that on Nov. 30, Amgen, manufacturer of the three ESAs -- Aranesp, Epogen, and Procrit -- provided the agency with information from the 733-patient PREPARE study of women who received chemotherapy before undergoing surgery for breast cancer. After three years, 14% of the patients given Aranesp to treat their anemia had died, compared with 9.8% who did not receive the drug. Tumor growth was also faster in patients given Aranesp.
On Dec. 4, Amgen informed the FDA of the results of a study by the National Cancer Institute's Gynecologic Oncology Group of patients receiving chemotherapy and radiation for advanced cervical cancer. The patients were given Procrit to maintain hemoglobin levels above 12 g/dL or transfusions as needed. After three years, 66% of the patients who did not take Procrit were alive and free of cancer growth compared with 58% given the drug.
Janet Woodcock, M.D., the FDA's chief medical officer and acting director of the Center for Drug Evaluation and Research, said the new information does not require immediate action, but does underscore "the safety concerns regarding use of ESAs in patients with cancer."
She said the FDA would discuss the new data at a planned advisory committee meeting on ESA safety "in the next few months."
Meanwhile, she said the FDA would continue to review available data and "may take additional action." She said physicians should "review the risks and benefits of ESAs outlined in the product label and discuss this information with their patients."
Amgen is based in Thousand Oaks, Calif. Procrit is marketed and distributed by Ortho Biotech LP of Bridgewater, N.J., a subsidiary of Johnson & Johnson.
By Peggy Peck
ROCKVILLE, Md., Jan. 3 -- More research has strengthened an association between erythropoiesis-stimulating agents (ESAs) and an increased risk of mortality when the drugs are used for chemotherapy-induced anemia, the FDA said today.
The new data came from two studies of women with breast cancer or advanced cervical cancer, research that had not been included when the FDA ordered a label change two months ago about excess mortality and/or rapid tumor growth with ESAs. This warning was on the basis of six other studies.
In today's statement, the FDA said that "all eight studies show more rapid tumor growth or shortened survival when patients with breast, non-small cell lung, head and neck, lymphoid, or cervical cancers received ESAs compared to patients who did not receive this treatment. In all of these recent studies, ESAs were administered in an attempt to achieve a hemoglobin level of 12 g/dL or greater, although many patients did not reach that level."
The FDA said that on Nov. 30, Amgen, manufacturer of the three ESAs -- Aranesp, Epogen, and Procrit -- provided the agency with information from the 733-patient PREPARE study of women who received chemotherapy before undergoing surgery for breast cancer. After three years, 14% of the patients given Aranesp to treat their anemia had died, compared with 9.8% who did not receive the drug. Tumor growth was also faster in patients given Aranesp.
On Dec. 4, Amgen informed the FDA of the results of a study by the National Cancer Institute's Gynecologic Oncology Group of patients receiving chemotherapy and radiation for advanced cervical cancer. The patients were given Procrit to maintain hemoglobin levels above 12 g/dL or transfusions as needed. After three years, 66% of the patients who did not take Procrit were alive and free of cancer growth compared with 58% given the drug.
Janet Woodcock, M.D., the FDA's chief medical officer and acting director of the Center for Drug Evaluation and Research, said the new information does not require immediate action, but does underscore "the safety concerns regarding use of ESAs in patients with cancer."
She said the FDA would discuss the new data at a planned advisory committee meeting on ESA safety "in the next few months."
Meanwhile, she said the FDA would continue to review available data and "may take additional action." She said physicians should "review the risks and benefits of ESAs outlined in the product label and discuss this information with their patients."
Amgen is based in Thousand Oaks, Calif. Procrit is marketed and distributed by Ortho Biotech LP of Bridgewater, N.J., a subsidiary of Johnson & Johnson.
Adjuvant Chemotherapy Backed for ER-Negative Breast Cancer
By Charles Bankhead
OXFORD, England, Jan. 3 -- For women of any age, adjuvant chemotherapy significantly reduces recurrence of estrogen receptor-negative breast cancer and increases survival, found an updated meta-analysis.
Given that the analysis evaluated trials of older chemotherapy regimens, greater benefits might be expected with newer and future therapies, Richard Peto, Ph.D., of the University of Oxford, and colleagues in the Early Breast Cancer Trialists' Collaborative Group reported in the Jan. 5 issue of The Lancet.
Breast tumors with a minimal volume of estrogen receptors (ER-poor) have a high recurrence rate after surgery, and hormonal therapy has little effect on recurrence, said Dr. Peto. Consequently, the impact of chemotherapy on such tumors has major implications for outcomes.
A single trial of adjuvant chemotherapy usually includes too few ER-poor (or ER-negative) patients for statistical stability, Dr. Peto continued. Treatments in these patients are best examined by periodically updated meta-analyses of all relevant randomized trials.
Since 1984-85, his group has performed meta-analyses every five years of centrally collected data on patients from all randomized trials of early breast cancer therapy. Analyses conducted in 1990 and 1995 showed that the benefits of adjuvant chemotherapy on long-term outcomes were greater in women younger than 50 than in older patients.
Results of the 2000 update demonstrated a greater benefit in older patients but were still insufficient for statistical reliability.
For the 2005-2006 update, the investigators analyzed data on about 6,000 women with ER-poor breast cancer from 46 trials of non-taxane combination chemotherapy and about 14,000 women with ER-poor breast cancer in 50 trials of tamoxifen versus chemotherapy or no adjuvant therapy. The trials had start dates of 1972 to 1993 and a median start date of 1982.
The analysis showed that combination chemotherapy significantly reduced recurrence, breast cancer mortality, and all-cause mortality in women younger than 50 at enrollment and in older patients. In patients younger than 50, combination chemotherapy significantly improved the following 10-year outcomes:
Recurrence, 33% versus 45% (risk ratio: 0.73, P<0.00001)
Breast cancer mortality, 24% versus 32% (RR: 0.73, P=0.0002)
Death from any cause, 25% versus 33% (RR: 0.75, P=0.0003)
Although older women were still underrepresented in the trials, adjuvant chemotherapy also led to significant improvement in 10-year outcomes when patients ages 50 to 59 and 60 to 69 were grouped together:
Recurrence, 42% versus 52% (RR: 0.82, P<0.00001)
Breast cancer mortality, 36% versus 42% (RR: 0.86, P=0.0004)
Death from any cause, 39% versus 45% (RR: 0.87, P=0.0009)
Tamoxifen had little effect on outcomes in women with ER-poor disease and did not significantly modify the effects of adjuvant chemotherapy, the authors said.
In an accompanying commentary, Rinat Yerushalmi, Ph.D., and Karen Gelmon, M.D., of the British Columbia Cancer Agency in Vancouver, said the latest update "further confirms the contribution of chemotherapy to decreasing recurrence of estrogen receptor-negative breast cancer. Efforts should now be directed towards the establishment of finer definitions of subtypes of such cancers, the study of less debilitating but active regimens, and the development of new strategies for those who are not cured by chemotherapy."
Neither the authors of the meta-analysis nor members of the steering committee disclosed any conflicts.
Drs. Yerushalmi and Gelmon declared no conflicts.
Primary source: The LancetSource reference:Early Breast Cancer Trialists' Collaborative Group "Adjuvant chemotherapy in estrogen-receptor-poor breast cancer: patient-level meta-analysis of randomized trials" Lancet 2008; 371: 29-40.
By Charles Bankhead
OXFORD, England, Jan. 3 -- For women of any age, adjuvant chemotherapy significantly reduces recurrence of estrogen receptor-negative breast cancer and increases survival, found an updated meta-analysis.
Given that the analysis evaluated trials of older chemotherapy regimens, greater benefits might be expected with newer and future therapies, Richard Peto, Ph.D., of the University of Oxford, and colleagues in the Early Breast Cancer Trialists' Collaborative Group reported in the Jan. 5 issue of The Lancet.
Breast tumors with a minimal volume of estrogen receptors (ER-poor) have a high recurrence rate after surgery, and hormonal therapy has little effect on recurrence, said Dr. Peto. Consequently, the impact of chemotherapy on such tumors has major implications for outcomes.
A single trial of adjuvant chemotherapy usually includes too few ER-poor (or ER-negative) patients for statistical stability, Dr. Peto continued. Treatments in these patients are best examined by periodically updated meta-analyses of all relevant randomized trials.
Since 1984-85, his group has performed meta-analyses every five years of centrally collected data on patients from all randomized trials of early breast cancer therapy. Analyses conducted in 1990 and 1995 showed that the benefits of adjuvant chemotherapy on long-term outcomes were greater in women younger than 50 than in older patients.
Results of the 2000 update demonstrated a greater benefit in older patients but were still insufficient for statistical reliability.
For the 2005-2006 update, the investigators analyzed data on about 6,000 women with ER-poor breast cancer from 46 trials of non-taxane combination chemotherapy and about 14,000 women with ER-poor breast cancer in 50 trials of tamoxifen versus chemotherapy or no adjuvant therapy. The trials had start dates of 1972 to 1993 and a median start date of 1982.
The analysis showed that combination chemotherapy significantly reduced recurrence, breast cancer mortality, and all-cause mortality in women younger than 50 at enrollment and in older patients. In patients younger than 50, combination chemotherapy significantly improved the following 10-year outcomes:
Recurrence, 33% versus 45% (risk ratio: 0.73, P<0.00001)
Breast cancer mortality, 24% versus 32% (RR: 0.73, P=0.0002)
Death from any cause, 25% versus 33% (RR: 0.75, P=0.0003)
Although older women were still underrepresented in the trials, adjuvant chemotherapy also led to significant improvement in 10-year outcomes when patients ages 50 to 59 and 60 to 69 were grouped together:
Recurrence, 42% versus 52% (RR: 0.82, P<0.00001)
Breast cancer mortality, 36% versus 42% (RR: 0.86, P=0.0004)
Death from any cause, 39% versus 45% (RR: 0.87, P=0.0009)
Tamoxifen had little effect on outcomes in women with ER-poor disease and did not significantly modify the effects of adjuvant chemotherapy, the authors said.
In an accompanying commentary, Rinat Yerushalmi, Ph.D., and Karen Gelmon, M.D., of the British Columbia Cancer Agency in Vancouver, said the latest update "further confirms the contribution of chemotherapy to decreasing recurrence of estrogen receptor-negative breast cancer. Efforts should now be directed towards the establishment of finer definitions of subtypes of such cancers, the study of less debilitating but active regimens, and the development of new strategies for those who are not cured by chemotherapy."
Neither the authors of the meta-analysis nor members of the steering committee disclosed any conflicts.
Drs. Yerushalmi and Gelmon declared no conflicts.
Primary source: The LancetSource reference:Early Breast Cancer Trialists' Collaborative Group "Adjuvant chemotherapy in estrogen-receptor-poor breast cancer: patient-level meta-analysis of randomized trials" Lancet 2008; 371: 29-40.
Androgen Deprivation May Improve Outcomes in Locally Advanced Prostate Cancer
Laurie Barclay, MD
January 2, 2008 — The addition of 4 months of androgen deprivation therapy (ADT) to external beam radiotherapy (EBRT) seems to have a dramatic impact on clinically meaningful endpoints in men with locally advanced prostate cancer without significantly increasing the risk for fatal cardiac events, according to the results of the Radiation Therapy Oncology Group (RTOG) 8610 study reported in the January 2 Early Release issue and will appear in the February 1 print issue of the Journal of Clinical Oncology.
"RTOG 8610 was the first major, phase III randomized trial to test the hypothesis that short-term neoadjuvant ADT combined with EBRT would improve treatment outcomes compared with EBRT alone," write Mack Roach III, MD, from the University of California San Francisco, and colleagues. "With relatively short follow-up, the addition of ADT was associated with an improvement in local control, a reduction in distant metastases, and cause-specific mortality. Herein, we update the long-term results of RTOG 8610 and confirm the important clinical benefits of adding short-term ADT to EBRT in patients with high-risk, locally advanced disease."
RTOG 8610 enrolled 456 assessable patients between 1987 and 1991. Median age was 70 years. Inclusion criteria, based on the 1988 American Joint Committee on Cancer Tumor, Node, Metastasis (TNM) staging system, were bulky (5 x 5 cm) tumors, stage T2-4, with or without pelvic lymph node involvement.
Patients were randomized to receive EBRT alone or with combined ADT, which consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg 3 times daily for 2 months before and during EBRT. The main outcome measures were overall survival, disease-specific mortality, distant metastases, disease-free survival, and biochemical failure.
At 10 years, estimates of overall survival (43% vs 34%) and median survival (8.7 vs 7.3 years) favored the combination of ADT plus EBRT vs EBRT alone. However, these differences were not statistically significant (P = .12). With the addition of ADT, improvements were observed in 10-year disease-specific mortality (23% vs 36%; P = .01), distant metastases (35% vs 47%; P = .006), disease-free survival (11% vs 3%; P < .0001), and biochemical failure (65% vs 80%; P < .0001).
The risk for fatal cardiac events was similar in both groups.
"The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events," the study authors write. "These updated findings of RTOG 8610 suggest that patients with high-risk, locally advanced disease who decline or who, for medical reasons, are not considered candidates for long-term ADT should be offered short-term neoadjuvant and concurrent ADT in combination with EBRT. The biologic rationale for using ADT with EBRT includes a reduction in the tumor volume and enhanced biologic effects."
The National Cancer Institute supported this study. Two of the study authors have disclosed various financial relationships with Astra-Zeneca.
J Clin Oncol. Published on January 2, 2008.2008;26:1-7.
Laurie Barclay, MD
January 2, 2008 — The addition of 4 months of androgen deprivation therapy (ADT) to external beam radiotherapy (EBRT) seems to have a dramatic impact on clinically meaningful endpoints in men with locally advanced prostate cancer without significantly increasing the risk for fatal cardiac events, according to the results of the Radiation Therapy Oncology Group (RTOG) 8610 study reported in the January 2 Early Release issue and will appear in the February 1 print issue of the Journal of Clinical Oncology.
"RTOG 8610 was the first major, phase III randomized trial to test the hypothesis that short-term neoadjuvant ADT combined with EBRT would improve treatment outcomes compared with EBRT alone," write Mack Roach III, MD, from the University of California San Francisco, and colleagues. "With relatively short follow-up, the addition of ADT was associated with an improvement in local control, a reduction in distant metastases, and cause-specific mortality. Herein, we update the long-term results of RTOG 8610 and confirm the important clinical benefits of adding short-term ADT to EBRT in patients with high-risk, locally advanced disease."
RTOG 8610 enrolled 456 assessable patients between 1987 and 1991. Median age was 70 years. Inclusion criteria, based on the 1988 American Joint Committee on Cancer Tumor, Node, Metastasis (TNM) staging system, were bulky (5 x 5 cm) tumors, stage T2-4, with or without pelvic lymph node involvement.
Patients were randomized to receive EBRT alone or with combined ADT, which consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg 3 times daily for 2 months before and during EBRT. The main outcome measures were overall survival, disease-specific mortality, distant metastases, disease-free survival, and biochemical failure.
At 10 years, estimates of overall survival (43% vs 34%) and median survival (8.7 vs 7.3 years) favored the combination of ADT plus EBRT vs EBRT alone. However, these differences were not statistically significant (P = .12). With the addition of ADT, improvements were observed in 10-year disease-specific mortality (23% vs 36%; P = .01), distant metastases (35% vs 47%; P = .006), disease-free survival (11% vs 3%; P < .0001), and biochemical failure (65% vs 80%; P < .0001).
The risk for fatal cardiac events was similar in both groups.
"The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events," the study authors write. "These updated findings of RTOG 8610 suggest that patients with high-risk, locally advanced disease who decline or who, for medical reasons, are not considered candidates for long-term ADT should be offered short-term neoadjuvant and concurrent ADT in combination with EBRT. The biologic rationale for using ADT with EBRT includes a reduction in the tumor volume and enhanced biologic effects."
The National Cancer Institute supported this study. Two of the study authors have disclosed various financial relationships with Astra-Zeneca.
J Clin Oncol. Published on January 2, 2008.2008;26:1-7.
TNAs Linked to Major Vascular Disease, Dementia Risk
Caroline Cassels
January 3, 2008 — Nonfocal transient neurologic attacks (TNAs) significantly increase the risk of major vascular disease and dementia – findings that contest the long-held belief that they are benign.
A large, prospective, population-based study showed patients who experienced TNAs with nonfocal symptoms, had approximately a 1.6-fold increased risk for stroke and dementia vs those without TNAs.
Furthermore, investigators found individuals with a combination of focal and nonfocal TNAs (also known as mixed symptoms) had a particularly poor prognosis with a high risk for stroke, vascular dementia, ischemic heart disease, and vascular death vs the referent group.
"Our findings challenge the strong but unfounded conviction that nonfocal TNAs are harmless. On the contrary, our findings suggest that nonfocal TNAs are not only a risk factor for stroke, but also for dementia," write Monique Breteler, MD, PhD, from the Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues.
The study is published in the December 26 issue of the Journal of the American Medical Association.
Although conventional diagnostic criteria for focal TNAs — otherwise known as transient ischemic attacks (TIAs) — are clear and well established, the classification and treatment of nonfocal TNAs remain uncertain.
The study authors note that symptoms of nonfocal TNA can include syncope, acute confusion, or transient global amnesia that have no known cause.
"Although the assumption that patients with TIA are at high risk of major vascular disease has repeatedly been confirmed since 1975, hardly any studies have challenged and verified the assumption that nonfocal TNAs have a benign clinical course," the investigators note.
Similar Incidence As TIAs
Part of the Rotterdam Study, a large, ongoing prospective cohort study investigating the prevalence and incidence of risk factors for chronic disease in elderly people, the aim of the current research was to determine the incidence and prognosis of focal, nonfocal, and mixed TNAs.
The study included 6062 participants 55 years or older who were free of stroke, myocardial infarction, and dementia at baseline (1990 - 1993).
All subjects were subsequently followed up for incident strokes, TIAs, ischemic heart disease, dementia, and death until January 1, 2005. Associations between incident TNAs and subsequent adverse events were then analyzed.
Of the total study group, a TNA occurred in 548 participants. Of these, 282 had a focal TNA, 228 had a nonfocal TNA, and 38 had a mixed TNA. The median age at the time of TNA was 79 years, and 69% of patients were women.
The study showed that nonfocal TNAs were almost as frequent as focal TNAs, with an incidence of 4.7 and 3.8 per 1000 person-years for focal and nonfocal TNAs, respectively. Furthermore, risk for both types of events strongly increased with advancing age.
With an incidence rate of 0.6 per 1000 person-years, mixed TNAs were less frequent and their relationship with age was less clear.
Rally Cry for More Evaluation, Research
In an accompanying editorial, S. Claiborne Johnston, MD, PhD, of the University of California, San Francisco, the prognosis of nonfocal TNA with its increased risk for stroke and vascular dementia may warrant more detailed assessment of such patients.
He notes a cholesterol panel, glucose level, hemoglobin A1c concentrations, and possible cardiac monitoring and echocardiography may help identify underlying risk factors for vascular disease in patients with nonfocal TNA.
With treatment, he adds, it may be that this patient group could also benefit from standard prevention practices recommended for patients with TIA including antiplatelet, statin, and antihypertensive therapy.
"Even though TNA is likely to be only of transient utility because clinicians must quickly move to more specific diagnoses to provide appropriate treatment for patients, this entity should be considered a rally cry for more extensive evaluation or consultation in those patients, as well as for further research," Dr. Johnston writes.
The Rotterdam Study is supported by Erasmus Medical Center Rotterdam; Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; and the Ministry of Health, Welfare, and Sports. The Netherlands Organization for Scientific Research supported this study. Three of the study authors have obtained funding. The remaining study authors have disclosed no relevant financial relationships.
Dr. Johnston has disclosed no relevant financial relationships.
JAMA. 2007;298:2877-2885, 2912-2913.
Caroline Cassels
January 3, 2008 — Nonfocal transient neurologic attacks (TNAs) significantly increase the risk of major vascular disease and dementia – findings that contest the long-held belief that they are benign.
A large, prospective, population-based study showed patients who experienced TNAs with nonfocal symptoms, had approximately a 1.6-fold increased risk for stroke and dementia vs those without TNAs.
Furthermore, investigators found individuals with a combination of focal and nonfocal TNAs (also known as mixed symptoms) had a particularly poor prognosis with a high risk for stroke, vascular dementia, ischemic heart disease, and vascular death vs the referent group.
"Our findings challenge the strong but unfounded conviction that nonfocal TNAs are harmless. On the contrary, our findings suggest that nonfocal TNAs are not only a risk factor for stroke, but also for dementia," write Monique Breteler, MD, PhD, from the Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues.
The study is published in the December 26 issue of the Journal of the American Medical Association.
Although conventional diagnostic criteria for focal TNAs — otherwise known as transient ischemic attacks (TIAs) — are clear and well established, the classification and treatment of nonfocal TNAs remain uncertain.
The study authors note that symptoms of nonfocal TNA can include syncope, acute confusion, or transient global amnesia that have no known cause.
"Although the assumption that patients with TIA are at high risk of major vascular disease has repeatedly been confirmed since 1975, hardly any studies have challenged and verified the assumption that nonfocal TNAs have a benign clinical course," the investigators note.
Similar Incidence As TIAs
Part of the Rotterdam Study, a large, ongoing prospective cohort study investigating the prevalence and incidence of risk factors for chronic disease in elderly people, the aim of the current research was to determine the incidence and prognosis of focal, nonfocal, and mixed TNAs.
The study included 6062 participants 55 years or older who were free of stroke, myocardial infarction, and dementia at baseline (1990 - 1993).
All subjects were subsequently followed up for incident strokes, TIAs, ischemic heart disease, dementia, and death until January 1, 2005. Associations between incident TNAs and subsequent adverse events were then analyzed.
Of the total study group, a TNA occurred in 548 participants. Of these, 282 had a focal TNA, 228 had a nonfocal TNA, and 38 had a mixed TNA. The median age at the time of TNA was 79 years, and 69% of patients were women.
The study showed that nonfocal TNAs were almost as frequent as focal TNAs, with an incidence of 4.7 and 3.8 per 1000 person-years for focal and nonfocal TNAs, respectively. Furthermore, risk for both types of events strongly increased with advancing age.
With an incidence rate of 0.6 per 1000 person-years, mixed TNAs were less frequent and their relationship with age was less clear.
Rally Cry for More Evaluation, Research
In an accompanying editorial, S. Claiborne Johnston, MD, PhD, of the University of California, San Francisco, the prognosis of nonfocal TNA with its increased risk for stroke and vascular dementia may warrant more detailed assessment of such patients.
He notes a cholesterol panel, glucose level, hemoglobin A1c concentrations, and possible cardiac monitoring and echocardiography may help identify underlying risk factors for vascular disease in patients with nonfocal TNA.
With treatment, he adds, it may be that this patient group could also benefit from standard prevention practices recommended for patients with TIA including antiplatelet, statin, and antihypertensive therapy.
"Even though TNA is likely to be only of transient utility because clinicians must quickly move to more specific diagnoses to provide appropriate treatment for patients, this entity should be considered a rally cry for more extensive evaluation or consultation in those patients, as well as for further research," Dr. Johnston writes.
The Rotterdam Study is supported by Erasmus Medical Center Rotterdam; Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; and the Ministry of Health, Welfare, and Sports. The Netherlands Organization for Scientific Research supported this study. Three of the study authors have obtained funding. The remaining study authors have disclosed no relevant financial relationships.
Dr. Johnston has disclosed no relevant financial relationships.
JAMA. 2007;298:2877-2885, 2912-2913.
Physical Activity Levels Linked to Reduced Stress With Ovarian Aging
Laurie Barclay
January 3, 2008 — High levels of physical activity in community-dwelling women were related to lower levels of stress, anxiety, and depression accompanying ovarian aging, but not to lower levels of vasomotor symptoms, according to the results of an ongoing, longitudinal cohort study, which is reported in the January issue of Medicine and Science in Sports and Exercise.
"Physical activity has been proposed as an intervention for preventing or attenuating menopause-related vasomotor symptoms as well as other psychological symptoms such as anxiety and depression but to date the evidence regarding the benefit of physical activity is varied," write Deborah B. Nelson, PhD, from Temple University in Philadelphia, Pennsylvania, and colleagues. "Current studies examining the usefulness of physical activity in preventing or attenuating vasomotor symptoms have been mixed and the number of studies assessing the role of physical activity on other symptoms such as depression, stress and anxiety has been minimal."
The objective of The Penn Study of Ovarian Aging study was to assess whether physical activity, measured by expended kilocalories per week (kcal/week), was associated with decreased risk for menopausal symptoms among African American and Caucasian women.
During an 8-year period, the investigators measured level of physical activity and menopausal symptoms, including hot flashes, depression, anxiety, stress, and vasomotor, physiologic, and somatic symptom summaries, in 401 women. Women in the top tertile of physical activity expended at least 1450 kcal/week; those in the middle tertile, 644 to 1450 kcal/week; and in the bottom tertile, less than 644 kcal/week.
At each period, regression models were used to estimate the independent effect of physical activity, after adjustment for covariates and hormone levels, on psychological and vasomotor symptoms. Results were stratified by menopausal status, race, and smoking status.
In the overall analysis, only perceived stress was associated with level of physical activity. Compared with women in the lowest tertile of activity, women in both the middle and top tertiles of physical activity reported lower mean levels of stress. Analysis by menopausal stage revealed that compared with inactive postmenopausal women, active postmenopausal women continued to report lower mean levels of anxiety, stress, and depressive symptoms.
There was no apparent association between level of physical activity and reports of hot flashes, even after adjustment for variability in hormonal changes.
"Among a cohort of community dwelling women, high levels of physical activity were related to lower levels of stress during an 8 year follow-up period," the study authors write. "In addition, levels of anxiety, stress and depression were lowest among physically active postmenopausal women compared to inactive women in the same menopausal grouping."
Limitations of the study include low prevalence of women with current depressive symptoms, resulting in insufficient power to detect associations of menopausal symptoms with physical activity in this subgroup; measurement of physical activity conducted approximately every 2 years during the 8-year follow-up period; both physical activity and hot flashes collected via self-report; use of a limited number of physical activity questions to estimate expended kcal/week; cross-sectional assessments of physical activity and menopausal symptoms; inability to examine the effect of current physical activity on the severity of hot flashes; lack of data regarding other personality characteristics including neuroticism or coping styles; and inability to adjust for the use of other types of complementary and alternative therapies.
"These results suggest that maintaining or increasing physical activity during the menopausal transitional period and postmenopause may assist in reducing a variety of psychological symptoms including anxiety, stress and depression," the study authors conclude. "It is possible that the conflicting findings regarding the effect of physical activity on vasomotor symptoms reported in the literature could be accounted for by variability in the changes in endogenous reproductive hormones given regular exercise above some undefined threshold. Additional studies of the effects of a wide range of physical activity levels, before and after the final menstrual period, on vasomotor menopausal symptoms that include measurements of reproductive hormones are needed to explore this hypothesis."
Med Sci Sports Exerc. 2008;00:000-000.
Laurie Barclay
January 3, 2008 — High levels of physical activity in community-dwelling women were related to lower levels of stress, anxiety, and depression accompanying ovarian aging, but not to lower levels of vasomotor symptoms, according to the results of an ongoing, longitudinal cohort study, which is reported in the January issue of Medicine and Science in Sports and Exercise.
"Physical activity has been proposed as an intervention for preventing or attenuating menopause-related vasomotor symptoms as well as other psychological symptoms such as anxiety and depression but to date the evidence regarding the benefit of physical activity is varied," write Deborah B. Nelson, PhD, from Temple University in Philadelphia, Pennsylvania, and colleagues. "Current studies examining the usefulness of physical activity in preventing or attenuating vasomotor symptoms have been mixed and the number of studies assessing the role of physical activity on other symptoms such as depression, stress and anxiety has been minimal."
The objective of The Penn Study of Ovarian Aging study was to assess whether physical activity, measured by expended kilocalories per week (kcal/week), was associated with decreased risk for menopausal symptoms among African American and Caucasian women.
During an 8-year period, the investigators measured level of physical activity and menopausal symptoms, including hot flashes, depression, anxiety, stress, and vasomotor, physiologic, and somatic symptom summaries, in 401 women. Women in the top tertile of physical activity expended at least 1450 kcal/week; those in the middle tertile, 644 to 1450 kcal/week; and in the bottom tertile, less than 644 kcal/week.
At each period, regression models were used to estimate the independent effect of physical activity, after adjustment for covariates and hormone levels, on psychological and vasomotor symptoms. Results were stratified by menopausal status, race, and smoking status.
In the overall analysis, only perceived stress was associated with level of physical activity. Compared with women in the lowest tertile of activity, women in both the middle and top tertiles of physical activity reported lower mean levels of stress. Analysis by menopausal stage revealed that compared with inactive postmenopausal women, active postmenopausal women continued to report lower mean levels of anxiety, stress, and depressive symptoms.
There was no apparent association between level of physical activity and reports of hot flashes, even after adjustment for variability in hormonal changes.
"Among a cohort of community dwelling women, high levels of physical activity were related to lower levels of stress during an 8 year follow-up period," the study authors write. "In addition, levels of anxiety, stress and depression were lowest among physically active postmenopausal women compared to inactive women in the same menopausal grouping."
Limitations of the study include low prevalence of women with current depressive symptoms, resulting in insufficient power to detect associations of menopausal symptoms with physical activity in this subgroup; measurement of physical activity conducted approximately every 2 years during the 8-year follow-up period; both physical activity and hot flashes collected via self-report; use of a limited number of physical activity questions to estimate expended kcal/week; cross-sectional assessments of physical activity and menopausal symptoms; inability to examine the effect of current physical activity on the severity of hot flashes; lack of data regarding other personality characteristics including neuroticism or coping styles; and inability to adjust for the use of other types of complementary and alternative therapies.
"These results suggest that maintaining or increasing physical activity during the menopausal transitional period and postmenopause may assist in reducing a variety of psychological symptoms including anxiety, stress and depression," the study authors conclude. "It is possible that the conflicting findings regarding the effect of physical activity on vasomotor symptoms reported in the literature could be accounted for by variability in the changes in endogenous reproductive hormones given regular exercise above some undefined threshold. Additional studies of the effects of a wide range of physical activity levels, before and after the final menstrual period, on vasomotor menopausal symptoms that include measurements of reproductive hormones are needed to explore this hypothesis."
Med Sci Sports Exerc. 2008;00:000-000.
Breast Cancer Gene Might Extend Ovarian Cancer Survival
THURSDAY, Jan. 3 (HealthDay News) -- Ashkenazi Jewish women with ovarian cancer live significantly longer if they carry specific mutations of the BRCA1 or BRCA2 genes known to raise risks for breast cancer.
After five years of following a group of Ashkenazi Jewish women with ovarian cancer, researchers reported that women with the BRCA1 or 2 mutations were 29 percent less likely to die from the disease.
The Israel-based research team compared five-year survival between 213 Ashkenazi ovarian cancer patients with BRCA1 or 2 mutations ("carriers") and 392 Ashkenazi ovarian cancer patients without the mutations ("non-carriers").
After five years of follow-up, almost half (46 percent) of the carriers had survived, compared with about a third (34.4 percent) of non-carriers. Median survival was almost 54 months for women carrying a mutation and just under 38 months for non-carriers. Survival differed most strongly for women diagnosed with more advanced disease (stage III or IV) -- carriers had five-year survival rates of 38.1 percent versus 24.5 percent for non-carriers. Other factors, such as age and tumor size, did not alter the effect of the genetic mutation.
The researchers also looked at ovarian cancer survival depending on whether women had a BRCA1 or a BRCA2 mutation. Women with BRCA1 mutations lived a median of just over 45 months, and women with BRCA2 mutations lived a median of 52.5 months, the study found.
"These findings are encouraging news for BRCA mutation carriers," Dr. Siegal Sadetzki, head of the Cancer & Radiation Epidemiology Unit at the Gertner Institute, Chaim Sheba Medical Center in Tel Hashomer, Israel, said in a prepared statement. "It's possible that patients with these mutations respond better to chemotherapy -- hopefully, once we learn more about the mechanisms of this response, tailoring individual treatment will further improve survival."
Normal BRCA1/2 genes control cell growth. Mutations in these genes, which are more common among Ashkenazi Jewish women than in the general population, increase the risk of breast and ovarian cancers. Ashkenazi Jews are of Eastern European descent.
The study is published in the January issue of the Journal of Clinical Oncology.
THURSDAY, Jan. 3 (HealthDay News) -- Ashkenazi Jewish women with ovarian cancer live significantly longer if they carry specific mutations of the BRCA1 or BRCA2 genes known to raise risks for breast cancer.
After five years of following a group of Ashkenazi Jewish women with ovarian cancer, researchers reported that women with the BRCA1 or 2 mutations were 29 percent less likely to die from the disease.
The Israel-based research team compared five-year survival between 213 Ashkenazi ovarian cancer patients with BRCA1 or 2 mutations ("carriers") and 392 Ashkenazi ovarian cancer patients without the mutations ("non-carriers").
After five years of follow-up, almost half (46 percent) of the carriers had survived, compared with about a third (34.4 percent) of non-carriers. Median survival was almost 54 months for women carrying a mutation and just under 38 months for non-carriers. Survival differed most strongly for women diagnosed with more advanced disease (stage III or IV) -- carriers had five-year survival rates of 38.1 percent versus 24.5 percent for non-carriers. Other factors, such as age and tumor size, did not alter the effect of the genetic mutation.
The researchers also looked at ovarian cancer survival depending on whether women had a BRCA1 or a BRCA2 mutation. Women with BRCA1 mutations lived a median of just over 45 months, and women with BRCA2 mutations lived a median of 52.5 months, the study found.
"These findings are encouraging news for BRCA mutation carriers," Dr. Siegal Sadetzki, head of the Cancer & Radiation Epidemiology Unit at the Gertner Institute, Chaim Sheba Medical Center in Tel Hashomer, Israel, said in a prepared statement. "It's possible that patients with these mutations respond better to chemotherapy -- hopefully, once we learn more about the mechanisms of this response, tailoring individual treatment will further improve survival."
Normal BRCA1/2 genes control cell growth. Mutations in these genes, which are more common among Ashkenazi Jewish women than in the general population, increase the risk of breast and ovarian cancers. Ashkenazi Jews are of Eastern European descent.
The study is published in the January issue of the Journal of Clinical Oncology.
Group sues FDA for stronger warnings
A consumer group sued the Food and Drug Administration Thursday, charging the agency is ignoring calls for stronger warnings that Cipro and similar antibiotics may cause serious tendon injuries.
Labels of the fluoroquinolone family of antibiotics — drugs that include the popular Cipro and Levaquin — already warn about rupture of tendons and other tendon injuries, but at the bottom of a list of other side effects.
The consumer group Public Citizen wants those warnings upgraded to the FDA's most severe type, a so-called black-box warning — and for patients to get pamphlets with every bottle that describe the risk. It argues that too few patients know they're supposed to quit using the drugs if they experience symptoms such as pain or inflammation, before the tendon actually ruptures.
Public Citizen filed a petition seeking the stronger warning in August 2006. The state of Illinois had filed a similar petition the previous year.
The FDA is violating its own statutes and putting patients at risk in taking so long to settle the issue, Public Citizen said in the suit filed in U.S. District Court for the District of Columbia.
When Public Citizen first filed the petition, FDA's database showed 262 reports of tendon ruptures between November 1997 and December 2005, along with hundreds of other tendon problems in users of these antibiotics. Since then, the FDA has received an additional 74 reports of tendon ruptures, said Public Citizen's Dr. Sidney Wolfe. Only a fraction of drug side effects typically are reported to the agency, he noted.
An FDA spokesman said the agency was evaluating the lawsuit and declined comment.
___
On the Net:
Food and Drug Administration: http://www.fda.gov/
A consumer group sued the Food and Drug Administration Thursday, charging the agency is ignoring calls for stronger warnings that Cipro and similar antibiotics may cause serious tendon injuries.
Labels of the fluoroquinolone family of antibiotics — drugs that include the popular Cipro and Levaquin — already warn about rupture of tendons and other tendon injuries, but at the bottom of a list of other side effects.
The consumer group Public Citizen wants those warnings upgraded to the FDA's most severe type, a so-called black-box warning — and for patients to get pamphlets with every bottle that describe the risk. It argues that too few patients know they're supposed to quit using the drugs if they experience symptoms such as pain or inflammation, before the tendon actually ruptures.
Public Citizen filed a petition seeking the stronger warning in August 2006. The state of Illinois had filed a similar petition the previous year.
The FDA is violating its own statutes and putting patients at risk in taking so long to settle the issue, Public Citizen said in the suit filed in U.S. District Court for the District of Columbia.
When Public Citizen first filed the petition, FDA's database showed 262 reports of tendon ruptures between November 1997 and December 2005, along with hundreds of other tendon problems in users of these antibiotics. Since then, the FDA has received an additional 74 reports of tendon ruptures, said Public Citizen's Dr. Sidney Wolfe. Only a fraction of drug side effects typically are reported to the agency, he noted.
An FDA spokesman said the agency was evaluating the lawsuit and declined comment.
___
On the Net:
Food and Drug Administration: http://www.fda.gov/
Thursday, January 03, 2008
Restless Legs Syndrome Linked to Cardiovascular Disease
By Crystal Phend
BOSTON, Jan. 2 -- Restless legs syndrome patients may be at twice the risk of stroke and heart disease as those without the movement disorder.The risk was greatest among those with the most severe and frequent symptoms, found John W. Winkelman, M.D., Ph.D., of Harvard and Brigham and Women's Hospital, and colleagues in a questionnaire-based study in the Jan. 1 issue of Neurology.However, Barbara Scherokman, M.D., a Fairfax, Va., neurologist and an American Academy of Neurology spokesperson, was skeptical. "This study should not cause patients to be overly fearful about heart attack or stroke because this is not definite proof of a connection," Dr. Scherokman said. "It is only suggestive."
The cross-sectional observational analysis included 1,559 men and 1,874 women (mean age 67.9) in the larger community-based Sleep Heart Health Study.
Overall, 5.2% of participants had restless legs syndrome -- defined by positive responses on a self-administered questionnaire to the four diagnostic criteria symptoms -- on at least five days per month that was associated with at least moderate distress.
Women were twice as likely to report restless legs syndrome as men (6.8% versus 3.3%).
Self-reported physician-diagnosed coronary artery disease was 2.05 times more common (95% confidence interval: 1.38 to 3.04) among patients with restless legs syndrome than those without it, after controlling for age, body mass index, diabetes, blood pressure, antihypertensive medication use, smoking, and other factors.
Likewise, physician-diagnosed cardiovascular disease was 2.07 times more common among those with restless legs syndrome (95% CI: 1.43 to 3.00).
After additional adjustment for apnea-hypopnea index, the associations were primarily among patients with at least 16 restless legs episodes per month.
Coronary artery disease was not significantly elevated in those with fewer episodes per month but was in those with 16 to 23 episodes (odds ratio: 3.18, 95% CI: 1.48 to 6.85) or more per month (OR: 2.71, 95% CI: 1.37 to 5.39).
Likewise, cardiovascular disease was more common only among those with episodes most days of the month (OR: 3.92, 95% CI: 1.92 to 8.03, and OR: 2.26, 95% CI: 1.17 to 4.37, respectively).
The associations strengthened with increasing bothersomeness of symptoms. Compared with patients without restless leg syndrome, the odds ratios were:
2.27 (95% CI: 1.26 to 4.09) for cardiovascular disease among those with moderately bothersome symptoms.
2.50 (95% CI: 1.38 to 4.54) for cardiovascular disease among those with "extremely" bothersome symptoms.
2.14 (95% CI: 1.13 to 4.03) for coronary artery disease among those with moderately bothersome symptoms.
2.32 (95% CI: 1.22 to 4.39) for coronary artery disease among those with "extremely" bothersome symptoms.
The authors pointed out that the Sleep Heart Health Study is a study of middle-age and older participants with a minimum age of 44. "Analyses stratified by age above or below 65 years suggest an effect modification by age, with the association of restless legs syndrome and cardiovascular disease seen only in the older age stratum."
Dr. Winkelman's group suggested that restless legs syndrome could cause cardiovascular disease and events through sleep deprivation or by spikes in nocturnal blood pressure during the repetitive arousals and limb movements commonly seen with restless leg syndrome.
However, they cautioned that the cross-sectional study design did not allow determination of causality or direction of causality. Also, diagnosis of restless leg syndrome was made by questionnaire rather than in a face-to-face interview.
"Although the questionnaire reflects currently accepted diagnostic criteria," they said, some patients with "clinical mimics" such as leg cramps, diabetic neuropathy, and arthritis were counted in the restless leg syndrome group, which could have inflated the association.
Furthermore, the results might not be generalizable to younger or non-white patients, they said.
The study was supported by the National Heart, Lung, and Blood Institute through cooperative agreements to several universities.
Dr. Winkelman reported being a consult to and conducting clinical trials research in restless legs syndrome sponsored by Boehringer Ingelheim, GlaxoSmithKline, and Schwarz Pharma.
Neither the other researchers nor Dr. Scherokman reported conflicts of interest.
Primary source: NeurologySource reference:Winkelman JW, et al "Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study" Neurology 2008; 70: 35-42.
By Crystal Phend
BOSTON, Jan. 2 -- Restless legs syndrome patients may be at twice the risk of stroke and heart disease as those without the movement disorder.The risk was greatest among those with the most severe and frequent symptoms, found John W. Winkelman, M.D., Ph.D., of Harvard and Brigham and Women's Hospital, and colleagues in a questionnaire-based study in the Jan. 1 issue of Neurology.However, Barbara Scherokman, M.D., a Fairfax, Va., neurologist and an American Academy of Neurology spokesperson, was skeptical. "This study should not cause patients to be overly fearful about heart attack or stroke because this is not definite proof of a connection," Dr. Scherokman said. "It is only suggestive."
The cross-sectional observational analysis included 1,559 men and 1,874 women (mean age 67.9) in the larger community-based Sleep Heart Health Study.
Overall, 5.2% of participants had restless legs syndrome -- defined by positive responses on a self-administered questionnaire to the four diagnostic criteria symptoms -- on at least five days per month that was associated with at least moderate distress.
Women were twice as likely to report restless legs syndrome as men (6.8% versus 3.3%).
Self-reported physician-diagnosed coronary artery disease was 2.05 times more common (95% confidence interval: 1.38 to 3.04) among patients with restless legs syndrome than those without it, after controlling for age, body mass index, diabetes, blood pressure, antihypertensive medication use, smoking, and other factors.
Likewise, physician-diagnosed cardiovascular disease was 2.07 times more common among those with restless legs syndrome (95% CI: 1.43 to 3.00).
After additional adjustment for apnea-hypopnea index, the associations were primarily among patients with at least 16 restless legs episodes per month.
Coronary artery disease was not significantly elevated in those with fewer episodes per month but was in those with 16 to 23 episodes (odds ratio: 3.18, 95% CI: 1.48 to 6.85) or more per month (OR: 2.71, 95% CI: 1.37 to 5.39).
Likewise, cardiovascular disease was more common only among those with episodes most days of the month (OR: 3.92, 95% CI: 1.92 to 8.03, and OR: 2.26, 95% CI: 1.17 to 4.37, respectively).
The associations strengthened with increasing bothersomeness of symptoms. Compared with patients without restless leg syndrome, the odds ratios were:
2.27 (95% CI: 1.26 to 4.09) for cardiovascular disease among those with moderately bothersome symptoms.
2.50 (95% CI: 1.38 to 4.54) for cardiovascular disease among those with "extremely" bothersome symptoms.
2.14 (95% CI: 1.13 to 4.03) for coronary artery disease among those with moderately bothersome symptoms.
2.32 (95% CI: 1.22 to 4.39) for coronary artery disease among those with "extremely" bothersome symptoms.
The authors pointed out that the Sleep Heart Health Study is a study of middle-age and older participants with a minimum age of 44. "Analyses stratified by age above or below 65 years suggest an effect modification by age, with the association of restless legs syndrome and cardiovascular disease seen only in the older age stratum."
Dr. Winkelman's group suggested that restless legs syndrome could cause cardiovascular disease and events through sleep deprivation or by spikes in nocturnal blood pressure during the repetitive arousals and limb movements commonly seen with restless leg syndrome.
However, they cautioned that the cross-sectional study design did not allow determination of causality or direction of causality. Also, diagnosis of restless leg syndrome was made by questionnaire rather than in a face-to-face interview.
"Although the questionnaire reflects currently accepted diagnostic criteria," they said, some patients with "clinical mimics" such as leg cramps, diabetic neuropathy, and arthritis were counted in the restless leg syndrome group, which could have inflated the association.
Furthermore, the results might not be generalizable to younger or non-white patients, they said.
The study was supported by the National Heart, Lung, and Blood Institute through cooperative agreements to several universities.
Dr. Winkelman reported being a consult to and conducting clinical trials research in restless legs syndrome sponsored by Boehringer Ingelheim, GlaxoSmithKline, and Schwarz Pharma.
Neither the other researchers nor Dr. Scherokman reported conflicts of interest.
Primary source: NeurologySource reference:Winkelman JW, et al "Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study" Neurology 2008; 70: 35-42.
Short-Term Testosterone Has Limited Effects in Aging Men
By Charles Bankhead
UTRECHT, Netherlands, Jan. 2 -- A daily dose of testosterone increased lean body mass, produced mixed metabolic effects, and had no effect on functional or cognitive status in older men, investigators here found.
Action Points --->
Explain to patients that testosterone supplementation improved lean body mass in older men but did not improve functional status or cognition.
Note that multiple studies of testosterone supplementation have yielded inconsistent results.
During six months of treatment, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group (P<0.001), Marielle H. Emmelot-Vonk, M.D., of the University of Utrecht, and colleagues reported in the Jan. 1 issue of the Journal of the American Medical Association.
Insulin sensitivity improved but HDL-cholesterol decreased and, by study end, the proportion of men meeting diagnostic criteria for metabolic syndrome trended higher in the testosterone group (47.8% versus 35.5%, odds ratio: 1.7, 95% CI: 0.97 to 2.8, P=0.07).
"The findings in this study do not support a net benefit on several indicators of health and functional and cognitive performance with six months of modest testosterone supplementation in healthy men with circulating testosterone levels in the lower range," the authors concluded.
The inconsistency of previous clinical trials of testosterone supplementation likely reflects differences in study design, the type and duration of treatment, and instruments employed to study aging, Dr. Emmelot-Vonk and colleagues stated.
Moreover, most studies had small sample sizes that limited power to detect differences in effects, and studies have had a limited scope, assessing only one or two aging-related outcomes, the authors continued.
The Institute of Medicine noted those limitations and other shortcomings in calling for more short-term, randomized, placebo-controlled clinical trials to examine the safety and efficacy of testosterone supplementation in aging men (National Academies Press, 2004).
So Dr. Emmelot-Vonk and colleagues conducted a blinded, randomized, placebo-controlled trial of testosterone supplementation in 237 healthy men ages 60 to 80. All study participants had testosterone levels <13.7 nmol/L and fell within the range of low-normal.
The men were randomized to 80 mg of testosterone twice daily for six months or a matching placebo regimen. All but 30 of the men completed the study.
Investigators examined the effects of testosterone supplementation on multiple outcomes: functional mobility (multiple tests), cognitive function (eight different tests), bone mineral density, body composition, metabolic risk factors, quality of life, and safety parameters.
Cognitive function and bone density did not change in the testosterone group relative to the placebo group.
Glucose, insulin, insulin sensitivity, and insulin resistance all improved significantly in the testosterone group compared with the placebo group (P=0.04 to P=0.007). However, HDL-cholesterol decreased from 1.2 mmol/L to 1.0 mmol/L in the testosterone group and remained unchanged in the placebo group (P<0.001).
The ratio of total cholesterol to HDL also was significantly higher in the men who received daily testosterone (P<0.001).
Quality-of-life measures did not differ between groups, and investigators found no evidence of a negative effect of testosterone in prostate safety.
Addressing limitations of the study, Dr. Emmelot-Vonk and co-authors acknowledged the brief period of follow-up, but they noted that other studies had demonstrated significant changes in outcomes within six months.
Additionally, they said, effects on supplementation should have been evident within six months for all but one of the endpoints chosen for the study (bone mineral density).
The testosterone dose used in the study was consistent with doses used in previous trials, they added. And, although testosterone levels in the blood did not increase among participants receiving the hormone, that was the experience in other studies as well.
"This study is, as far as we know, the largest study of testosterone supplementation with the most endpoints and a randomized, double-blind design," the investigators concluded. "Adherence was high and the dropout rate was low."
The study was supported by the Netherlands Organization for Health Research and Development and by Organon.
The authors reported no financial disclosures.
Primary source: JAMASource reference:Emmelot-Vonk MH, et al "Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men" JAMA 2008; 299: 39-52.
By Charles Bankhead
UTRECHT, Netherlands, Jan. 2 -- A daily dose of testosterone increased lean body mass, produced mixed metabolic effects, and had no effect on functional or cognitive status in older men, investigators here found.
Action Points --->
Explain to patients that testosterone supplementation improved lean body mass in older men but did not improve functional status or cognition.
Note that multiple studies of testosterone supplementation have yielded inconsistent results.
During six months of treatment, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group (P<0.001), Marielle H. Emmelot-Vonk, M.D., of the University of Utrecht, and colleagues reported in the Jan. 1 issue of the Journal of the American Medical Association.
Insulin sensitivity improved but HDL-cholesterol decreased and, by study end, the proportion of men meeting diagnostic criteria for metabolic syndrome trended higher in the testosterone group (47.8% versus 35.5%, odds ratio: 1.7, 95% CI: 0.97 to 2.8, P=0.07).
"The findings in this study do not support a net benefit on several indicators of health and functional and cognitive performance with six months of modest testosterone supplementation in healthy men with circulating testosterone levels in the lower range," the authors concluded.
The inconsistency of previous clinical trials of testosterone supplementation likely reflects differences in study design, the type and duration of treatment, and instruments employed to study aging, Dr. Emmelot-Vonk and colleagues stated.
Moreover, most studies had small sample sizes that limited power to detect differences in effects, and studies have had a limited scope, assessing only one or two aging-related outcomes, the authors continued.
The Institute of Medicine noted those limitations and other shortcomings in calling for more short-term, randomized, placebo-controlled clinical trials to examine the safety and efficacy of testosterone supplementation in aging men (National Academies Press, 2004).
So Dr. Emmelot-Vonk and colleagues conducted a blinded, randomized, placebo-controlled trial of testosterone supplementation in 237 healthy men ages 60 to 80. All study participants had testosterone levels <13.7 nmol/L and fell within the range of low-normal.
The men were randomized to 80 mg of testosterone twice daily for six months or a matching placebo regimen. All but 30 of the men completed the study.
Investigators examined the effects of testosterone supplementation on multiple outcomes: functional mobility (multiple tests), cognitive function (eight different tests), bone mineral density, body composition, metabolic risk factors, quality of life, and safety parameters.
Cognitive function and bone density did not change in the testosterone group relative to the placebo group.
Glucose, insulin, insulin sensitivity, and insulin resistance all improved significantly in the testosterone group compared with the placebo group (P=0.04 to P=0.007). However, HDL-cholesterol decreased from 1.2 mmol/L to 1.0 mmol/L in the testosterone group and remained unchanged in the placebo group (P<0.001).
The ratio of total cholesterol to HDL also was significantly higher in the men who received daily testosterone (P<0.001).
Quality-of-life measures did not differ between groups, and investigators found no evidence of a negative effect of testosterone in prostate safety.
Addressing limitations of the study, Dr. Emmelot-Vonk and co-authors acknowledged the brief period of follow-up, but they noted that other studies had demonstrated significant changes in outcomes within six months.
Additionally, they said, effects on supplementation should have been evident within six months for all but one of the endpoints chosen for the study (bone mineral density).
The testosterone dose used in the study was consistent with doses used in previous trials, they added. And, although testosterone levels in the blood did not increase among participants receiving the hormone, that was the experience in other studies as well.
"This study is, as far as we know, the largest study of testosterone supplementation with the most endpoints and a randomized, double-blind design," the investigators concluded. "Adherence was high and the dropout rate was low."
The study was supported by the Netherlands Organization for Health Research and Development and by Organon.
The authors reported no financial disclosures.
Primary source: JAMASource reference:Emmelot-Vonk MH, et al "Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men" JAMA 2008; 299: 39-52.
FDA Okays Rapid Blood Test for MRSA
By Todd Neale
ROCKVILLE, Md., Jan. 2 -- The FDA today approved the first rapid blood test for methicillin-resistant Staphylococcus aureus (MRSA).
The BD GeneOhm StaphSR Assay can determine within two hours whether genetic material in a blood sample belongs to MRSA or a more treatable staph bacterium, according to the FDA. Tests currently used can take more than two days.
In October, the CDC announced a revised estimate of 94,360 invasive MRSA infections in 2005, up from 31,440 in 2000. (See: Invasive MRSA More Pervasive Than Suspected)
This was preceded by public concerns about the apparent rise of community-acquired MRSA.
The new test was cleared on the basis of a clinical trial that showed that the assay identified 100% of the MRSA specimens and 98% of the less dangerous staph bacteria.
By Todd Neale
ROCKVILLE, Md., Jan. 2 -- The FDA today approved the first rapid blood test for methicillin-resistant Staphylococcus aureus (MRSA).
The BD GeneOhm StaphSR Assay can determine within two hours whether genetic material in a blood sample belongs to MRSA or a more treatable staph bacterium, according to the FDA. Tests currently used can take more than two days.
In October, the CDC announced a revised estimate of 94,360 invasive MRSA infections in 2005, up from 31,440 in 2000. (See: Invasive MRSA More Pervasive Than Suspected)
This was preceded by public concerns about the apparent rise of community-acquired MRSA.
The new test was cleared on the basis of a clinical trial that showed that the assay identified 100% of the MRSA specimens and 98% of the less dangerous staph bacteria.
Different Metabolic Effects Observed With Traditional and Atkins-Like Diets
Michael O'Riordan
January 2, 2008 (Adelaide, Australia) – A study comparing the metabolic effects of two diets, one a low-carbohydrate, high-fat, Atkins-like diet and the other a more traditional high-carbohydrate, low-fat diet, showed that both diets had similar improvements on a number of metabolic risk markers, although the traditional diet had more favorable effects on the blood lipid profile, including significant reductions in LDL-cholesterol levels [1].
"After six months, isocaloric energy-restricted very-low-carbohydrate, high-fat and high-carbohydrate, low-fat diets produced similar weight loss and substantial reductions in a number of cardiovascular disease risk markers," write Jeannie Tay (Flinders University, Adelaide, Australia) and colleagues in the January 1, 2008 issue of the Journal of the American College of Cardiology. "Neither diet displayed adverse effects, suggesting diverse dietary patterns, including very-low-carbohydrate, high-fat diets, may be tailored to an individual's metabolic profile and dietary preference for weight management."
The investigators note that while the traditional diet reduced LDL-cholesterol levels, the low-carbohydrate, high-fat diet resulted in greater increases in HDL cholesterol and larger reductions in triacylglycerol levels.
Weight loss as a confounding factor
As previously reported by heartwire, several studies have demonstrated greater weight loss among subjects who adhere to a low-carbohydrate, high-fat diet, such as the popular Atkins diet. One recent study, known as the Atkins-Traditional-Ornish-Zone (A TO Z) trial, found that premenopausal women randomized to the Atkins diet lost statistically more weight than women on the Zone diet and numerically more than the other two diets [2].
Despite the potential weight-loss advantages, there is still concern that long-term consumption of a high-fat diet, one high in saturated fat and cholesterol, will have adverse effects on blood lipids and cardiovascular disease risk. In this study, Tay and colleagues aimed to examine the metabolic effects of a low-carbohydrate, high-fat diet without the confounding effect of differential weight loss. The investigators compared the metabolic effects of the two diets, a traditional vs low-carbohydrate, high-fat one, under controlled dietary conditions where 88 subjects with abdominal obesity and at least one additional metabolic-syndrome risk factor consumed roughly the same amount of calories over a six-month period.
The subjects were randomly assigned to either of the moderately energy-restricted diet plans for 24 weeks. For those assigned to the very-low-carbohydrate, high-fat diet, 4% of total calories were obtained from carbohydrates, 35% from protein, and 61% from fat, including 20% from saturated fat. Subjects randomized to the high-carbohydrate, low-fat diet followed a more traditional macronutrient profile, with 46% of calories obtained from carbohydrates and 30% from fat, including <8% from saturated fat. Both treatment arms consumed the same number of calories daily.
Over the 24 weeks, there were significant reductions in body weight in both groups, but no significant difference between the two diets, either in absolute or relative terms. Total- and LDL-cholesterol levels decreased among subjects randomized to the low-fat diet but did not change significantly among those randomized to the Atkins-like diet. Those who consumed a high-fat, low-carbohydrate diet did experience greater increases in HDL-cholesterol levels as well as a greater reduction in triacylglycerol levels. Blood pressure, fasting glucose, insulin, and homeostasis model assessment were all reduced with weight loss, with no difference observed between the diets.
The investigators suggest that the anticipated increase in LDL cholesterol in the high-fat intervention arm, a result of higher saturated-fat intake, might have been mitigated by the effects of energy restriction and weight loss. However, there was no observed correlation between the change in LDL-cholesterol levels and the change in saturated-fat intake or weight, "suggesting the influence of other factors." They also note that there was wide variability in the LDL response in the low-carbohydrate, high-fat-diet arm, with approximately one-half of subjects showing a decrease. This suggests, Tay and colleagues write, that some individuals might have a more sensitive lipoprotein response to increases in saturated-fat intake.
Tay J, Brinkworth GD, Noakes M, et al. Metabolic effects of weight loss on a very-low-carbohydrate diet compared with an isocaloric high-carbohydrate diet in abdominally obese subjects. J Am Coll Cardiol 2008; 51: 59-67.
Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA 2007; 297: 969-977. Abstract
Michael O'Riordan
January 2, 2008 (Adelaide, Australia) – A study comparing the metabolic effects of two diets, one a low-carbohydrate, high-fat, Atkins-like diet and the other a more traditional high-carbohydrate, low-fat diet, showed that both diets had similar improvements on a number of metabolic risk markers, although the traditional diet had more favorable effects on the blood lipid profile, including significant reductions in LDL-cholesterol levels [1].
"After six months, isocaloric energy-restricted very-low-carbohydrate, high-fat and high-carbohydrate, low-fat diets produced similar weight loss and substantial reductions in a number of cardiovascular disease risk markers," write Jeannie Tay (Flinders University, Adelaide, Australia) and colleagues in the January 1, 2008 issue of the Journal of the American College of Cardiology. "Neither diet displayed adverse effects, suggesting diverse dietary patterns, including very-low-carbohydrate, high-fat diets, may be tailored to an individual's metabolic profile and dietary preference for weight management."
The investigators note that while the traditional diet reduced LDL-cholesterol levels, the low-carbohydrate, high-fat diet resulted in greater increases in HDL cholesterol and larger reductions in triacylglycerol levels.
Weight loss as a confounding factor
As previously reported by heartwire, several studies have demonstrated greater weight loss among subjects who adhere to a low-carbohydrate, high-fat diet, such as the popular Atkins diet. One recent study, known as the Atkins-Traditional-Ornish-Zone (A TO Z) trial, found that premenopausal women randomized to the Atkins diet lost statistically more weight than women on the Zone diet and numerically more than the other two diets [2].
Despite the potential weight-loss advantages, there is still concern that long-term consumption of a high-fat diet, one high in saturated fat and cholesterol, will have adverse effects on blood lipids and cardiovascular disease risk. In this study, Tay and colleagues aimed to examine the metabolic effects of a low-carbohydrate, high-fat diet without the confounding effect of differential weight loss. The investigators compared the metabolic effects of the two diets, a traditional vs low-carbohydrate, high-fat one, under controlled dietary conditions where 88 subjects with abdominal obesity and at least one additional metabolic-syndrome risk factor consumed roughly the same amount of calories over a six-month period.
The subjects were randomly assigned to either of the moderately energy-restricted diet plans for 24 weeks. For those assigned to the very-low-carbohydrate, high-fat diet, 4% of total calories were obtained from carbohydrates, 35% from protein, and 61% from fat, including 20% from saturated fat. Subjects randomized to the high-carbohydrate, low-fat diet followed a more traditional macronutrient profile, with 46% of calories obtained from carbohydrates and 30% from fat, including <8% from saturated fat. Both treatment arms consumed the same number of calories daily.
Over the 24 weeks, there were significant reductions in body weight in both groups, but no significant difference between the two diets, either in absolute or relative terms. Total- and LDL-cholesterol levels decreased among subjects randomized to the low-fat diet but did not change significantly among those randomized to the Atkins-like diet. Those who consumed a high-fat, low-carbohydrate diet did experience greater increases in HDL-cholesterol levels as well as a greater reduction in triacylglycerol levels. Blood pressure, fasting glucose, insulin, and homeostasis model assessment were all reduced with weight loss, with no difference observed between the diets.
The investigators suggest that the anticipated increase in LDL cholesterol in the high-fat intervention arm, a result of higher saturated-fat intake, might have been mitigated by the effects of energy restriction and weight loss. However, there was no observed correlation between the change in LDL-cholesterol levels and the change in saturated-fat intake or weight, "suggesting the influence of other factors." They also note that there was wide variability in the LDL response in the low-carbohydrate, high-fat-diet arm, with approximately one-half of subjects showing a decrease. This suggests, Tay and colleagues write, that some individuals might have a more sensitive lipoprotein response to increases in saturated-fat intake.
Tay J, Brinkworth GD, Noakes M, et al. Metabolic effects of weight loss on a very-low-carbohydrate diet compared with an isocaloric high-carbohydrate diet in abdominally obese subjects. J Am Coll Cardiol 2008; 51: 59-67.
Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA 2007; 297: 969-977. Abstract
Hospital Cardiac Arrest Response Often Too Slow
By DENISE GRADY
When patients in the hospital suddenly go into cardiac arrest, the staff often takes too long to respond, increasing the risk of brain damage and death, a new study finds.
The research, being published on Thursday in The New England Journal of Medicine, has implications for several hundred thousand people a year in the United States
Doctors analyzed the records of 6,789 patients at 369 hospitals whose hearts stopped because of conditions that could be reversed with an electrical shock from a defibrillator — a favorite device in TV hospital dramas, when a “code blue” is called and doctors and nurses come running with a crash cart and paddles to shock the victim back to life.
In the real world, doctors and nurses do not always run fast enough. Expert guidelines say the shock should be given within two minutes after the heart stops, but the study found that it took longer in 30 percent of the cases. The consequences were striking. When the defibrillation was delayed, only 22.2 percent of the patients survived long enough to be discharged from the hospital, as opposed to 39.3 percent when the shock was given on time.
Delays were more likely in patients whose hearts stopped at night or on the weekend, who were admitted for noncardiac illnesses, in hospitals with fewer than 250 beds and in units without heart monitors.
Being black also increased the odds of a delay, but the researchers said that finding probably reflected the type of hospitals in areas where most blacks live and are treated, rather than a decision by medical staff to drag their feet because of a patient’s race.
Nationwide, the problem may be even worse, with delays more common than the 30 percent figure in the study, said Dr. Paul S. Chan, an author of the report, from Saint Luke’s Mid-America Heart Institute in Kansas City, Mo., and the University of Michigan. He said the hospitals in the study probably performed better than average, because all had joined a national registry on cardiac arrest, meaning that they were already putting special efforts into trying to meet resuscitation guidelines.
The registry, created by the American Heart Association, keeps the data anonymous, Dr. Chan said, so it not possible to name hospitals that performed especially well or poorly in the study.
In an editorial accompanying the study, Dr. Leslie A. Saxon, the chief of cardiology at the University of Southern California, said most people probably assumed that a hospital would be the safest place to have a cardiac arrest. But, she said, the assumption turns out to be incorrect.
“I think it’s something doctors have always known but not thought about,” she said, adding that Dr. Chan’s team had conducted a “great study” that would help doctors recognize the problem.
“This is the kind of data we need to say, let’s make sure these preventable things never happen on our watch,” Dr. Saxon said.
From 370,000 to 750,000 hospitalized patients have a cardiac arrest and undergo resuscitation every year in the United States. In about half, the arrest is caused by an abnormal, too-fast rhythm that can be corrected with a shock, Dr. Chan said; the rest need drugs or other treatments.
Dr. Chan said: “We know what works, what saves lives. We have the technology available, and certainly the knowledge and skilled personnel in the hospital to shock patients back to normal rhythm.”
But it will take “political will” for hospitals to put those resources to better use, he said.
Dr. Chan said researchers thought they knew some of the reasons for delays. Sometimes, he said, especially nights and weekends, not enough personnel were available. In some hospitals, nurses outside the intensive care unit are not allowed to use defibrillators, and must wait for a doctor to show up.
“In a small hospital in the middle of the night, the only doctor may be in the emergency room,” Dr. Chan said.
He said hospitals with the best track records might keep their staffs sharp by conducting resuscitation drills or “mock codes,” and might have rapid-response teams, which are specially trained groups that take care of all cardiac arrests.
Another factor is the type and amount of resuscitation equipment available, he said. Traditional defibrillators used in hospitals require that a doctor or nurse look at the patient’s electrocardiogram, verify that the problem is “shockable,” adjust the machine and deliver the shock.
By contrast, the automatic defibrillators that have come into use in public places like airports and casinos during the past decade or so are meant to be used by ordinary people — trained employees or even bystanders. Connected to the chest of someone who has collapsed, the machine senses electrical activity in the heart and delivers a shock only if it is needed. These devices are designed to be essentially foolproof and to make it impossible to harm someone by firing off an unnecessary shock.
Dr. Saxon said the technology existed to offer more people the type of heart monitoring now given mostly to cardiac patients. Not everyone needs it, she said, but it may be in order for those who are very ill with kidney problems, diabetes or pneumonia, even without a history of heart problems. Their information would be transmitted to a computer network that would send out an alert if needed. In addition, she said, automatic defibrillators could be installed in every hospital room.
“You can get them for $500 on eBay,” she said. “It wouldn’t even take a nurse. You could train the cafeteria workers if you wanted to.”
By DENISE GRADY
When patients in the hospital suddenly go into cardiac arrest, the staff often takes too long to respond, increasing the risk of brain damage and death, a new study finds.
The research, being published on Thursday in The New England Journal of Medicine, has implications for several hundred thousand people a year in the United States
Doctors analyzed the records of 6,789 patients at 369 hospitals whose hearts stopped because of conditions that could be reversed with an electrical shock from a defibrillator — a favorite device in TV hospital dramas, when a “code blue” is called and doctors and nurses come running with a crash cart and paddles to shock the victim back to life.
In the real world, doctors and nurses do not always run fast enough. Expert guidelines say the shock should be given within two minutes after the heart stops, but the study found that it took longer in 30 percent of the cases. The consequences were striking. When the defibrillation was delayed, only 22.2 percent of the patients survived long enough to be discharged from the hospital, as opposed to 39.3 percent when the shock was given on time.
Delays were more likely in patients whose hearts stopped at night or on the weekend, who were admitted for noncardiac illnesses, in hospitals with fewer than 250 beds and in units without heart monitors.
Being black also increased the odds of a delay, but the researchers said that finding probably reflected the type of hospitals in areas where most blacks live and are treated, rather than a decision by medical staff to drag their feet because of a patient’s race.
Nationwide, the problem may be even worse, with delays more common than the 30 percent figure in the study, said Dr. Paul S. Chan, an author of the report, from Saint Luke’s Mid-America Heart Institute in Kansas City, Mo., and the University of Michigan. He said the hospitals in the study probably performed better than average, because all had joined a national registry on cardiac arrest, meaning that they were already putting special efforts into trying to meet resuscitation guidelines.
The registry, created by the American Heart Association, keeps the data anonymous, Dr. Chan said, so it not possible to name hospitals that performed especially well or poorly in the study.
In an editorial accompanying the study, Dr. Leslie A. Saxon, the chief of cardiology at the University of Southern California, said most people probably assumed that a hospital would be the safest place to have a cardiac arrest. But, she said, the assumption turns out to be incorrect.
“I think it’s something doctors have always known but not thought about,” she said, adding that Dr. Chan’s team had conducted a “great study” that would help doctors recognize the problem.
“This is the kind of data we need to say, let’s make sure these preventable things never happen on our watch,” Dr. Saxon said.
From 370,000 to 750,000 hospitalized patients have a cardiac arrest and undergo resuscitation every year in the United States. In about half, the arrest is caused by an abnormal, too-fast rhythm that can be corrected with a shock, Dr. Chan said; the rest need drugs or other treatments.
Dr. Chan said: “We know what works, what saves lives. We have the technology available, and certainly the knowledge and skilled personnel in the hospital to shock patients back to normal rhythm.”
But it will take “political will” for hospitals to put those resources to better use, he said.
Dr. Chan said researchers thought they knew some of the reasons for delays. Sometimes, he said, especially nights and weekends, not enough personnel were available. In some hospitals, nurses outside the intensive care unit are not allowed to use defibrillators, and must wait for a doctor to show up.
“In a small hospital in the middle of the night, the only doctor may be in the emergency room,” Dr. Chan said.
He said hospitals with the best track records might keep their staffs sharp by conducting resuscitation drills or “mock codes,” and might have rapid-response teams, which are specially trained groups that take care of all cardiac arrests.
Another factor is the type and amount of resuscitation equipment available, he said. Traditional defibrillators used in hospitals require that a doctor or nurse look at the patient’s electrocardiogram, verify that the problem is “shockable,” adjust the machine and deliver the shock.
By contrast, the automatic defibrillators that have come into use in public places like airports and casinos during the past decade or so are meant to be used by ordinary people — trained employees or even bystanders. Connected to the chest of someone who has collapsed, the machine senses electrical activity in the heart and delivers a shock only if it is needed. These devices are designed to be essentially foolproof and to make it impossible to harm someone by firing off an unnecessary shock.
Dr. Saxon said the technology existed to offer more people the type of heart monitoring now given mostly to cardiac patients. Not everyone needs it, she said, but it may be in order for those who are very ill with kidney problems, diabetes or pneumonia, even without a history of heart problems. Their information would be transmitted to a computer network that would send out an alert if needed. In addition, she said, automatic defibrillators could be installed in every hospital room.
“You can get them for $500 on eBay,” she said. “It wouldn’t even take a nurse. You could train the cafeteria workers if you wanted to.”
Egypt: 4 Women Die of Bird Flu
By DONALD G. McNEIL Jr.
Bird flu has killed four Egyptian women in the past week, according to Egyptian health officials and the World Health Organization. The women, ages 25 to 50, were from different provinces, and the cases were not related, officials said. At least one was a chicken seller, and the others were said to have kept poultry at home. The H5N1 strain of avian flu appears endemic in Egyptian poultry; previously the last human case was in June. A total of 43 Egyptians have been infected with H5N1 since it arrived in early 2006; 19 died.
By DONALD G. McNEIL Jr.
Bird flu has killed four Egyptian women in the past week, according to Egyptian health officials and the World Health Organization. The women, ages 25 to 50, were from different provinces, and the cases were not related, officials said. At least one was a chicken seller, and the others were said to have kept poultry at home. The H5N1 strain of avian flu appears endemic in Egyptian poultry; previously the last human case was in June. A total of 43 Egyptians have been infected with H5N1 since it arrived in early 2006; 19 died.
Elderly at risk of memory trouble after surgery
People 60 and older who undergo elective surgery may be at higher risk of lasting memory problems, U.S. researchers said on Wednesday.
They said people 60 and older who have major surgeries such as joint replacements or hysterectomies are more likely to have cognitive problems after surgery.
And those who do are more likely to die in the first year after their surgery.
"We have known that patients undergoing heart surgery are at risk for cognitive dysfunction -- problems with memory, concentration, processing of information -- but the effects of non-cardiac surgeries on brain function are not as well-understood," said Dr. Terri Monk, an anesthesiologist at Duke University Medical Center, whose study appears in the journal Anesthesiology.
Monk led a team that examined hospital discharge records of 1,064 patients aged 18 and older who underwent testing for memory and cognitive function before surgery, at the time of discharge from the hospital and three months later.
They were put into three age groups: young (18-39), middle-aged (40-59) and elderly (60 and older). The groups were all of similar size.
Three months after surgery, cognitive deficits occurred in 12.7 percent of elderly patients, compared with just 5.7 percent of those in the young group or 5.6 percent in the middle-aged group.
The study suggests that overall, some 30 to 41 percent of adult patients undergoing major non-cardiac surgery have some form of memory or processing problem when they are discharged, but most people recover after three months.
But those 60 and older were more than twice as likely to still have problems three months after surgery. And those that had problems were more likely to die within the first year after surgery.
It is not clear why some patients suffer these problems, but it may be that surgery and anesthesia cause swelling in the brain that can affect the patient's ability to learn, retain or remember information, Monk said in a statement.
She said the study suggests the elderly may be predisposed to cognitive problems after major surgery. And knowing this might help doctors devise better strategies to prevent the effects of surgery and anesthesia on the aging brain.
People 60 and older who undergo elective surgery may be at higher risk of lasting memory problems, U.S. researchers said on Wednesday.
They said people 60 and older who have major surgeries such as joint replacements or hysterectomies are more likely to have cognitive problems after surgery.
And those who do are more likely to die in the first year after their surgery.
"We have known that patients undergoing heart surgery are at risk for cognitive dysfunction -- problems with memory, concentration, processing of information -- but the effects of non-cardiac surgeries on brain function are not as well-understood," said Dr. Terri Monk, an anesthesiologist at Duke University Medical Center, whose study appears in the journal Anesthesiology.
Monk led a team that examined hospital discharge records of 1,064 patients aged 18 and older who underwent testing for memory and cognitive function before surgery, at the time of discharge from the hospital and three months later.
They were put into three age groups: young (18-39), middle-aged (40-59) and elderly (60 and older). The groups were all of similar size.
Three months after surgery, cognitive deficits occurred in 12.7 percent of elderly patients, compared with just 5.7 percent of those in the young group or 5.6 percent in the middle-aged group.
The study suggests that overall, some 30 to 41 percent of adult patients undergoing major non-cardiac surgery have some form of memory or processing problem when they are discharged, but most people recover after three months.
But those 60 and older were more than twice as likely to still have problems three months after surgery. And those that had problems were more likely to die within the first year after surgery.
It is not clear why some patients suffer these problems, but it may be that surgery and anesthesia cause swelling in the brain that can affect the patient's ability to learn, retain or remember information, Monk said in a statement.
She said the study suggests the elderly may be predisposed to cognitive problems after major surgery. And knowing this might help doctors devise better strategies to prevent the effects of surgery and anesthesia on the aging brain.
Wednesday, January 02, 2008
Combo Therapy Surpasses Single Drug for Severe COPD
By Judith Groch
LONDON, Dec. 28 -- Combination drug therapy with salmeterol (Serevent), a long-acting inhaled bronchodilator, and fluticasone (Flovent) improved survival and led to fewer treatment withdrawals compared with single-drug therapy in severe COPD. A multicenter head-to-head study found a 52% reduction in the risk of all-cause mortality at any time during the study for the combo treatment compared with single-drug treatment, Jadwiga A. Wedzicha, M.D., of Royal Free & University College Medical School here, and colleagues reported in the first January issue of the American Journal of Critical Care Medicine Significantly, however, exacerbations, which are key drivers of morbidity and mortality, were similar for the two regimens, the researchers reported.
The study, Investigating New Standards for Prophylaxis in Reducing Exacerbations (INSPIRE), compared the relative efficacy of the combination treatment with monotherapy with the long-acting bronchodilator tiotropium (Spiriva).
In a two-year, double-blind, double-dummy parallel study, 1,323 patients (mean age, 64, post-bronchodilator FEV1, 39% predicted) were randomized to receive either the combination of salmeterol/ fluticasone (50/500 μg twice daily) or tiotropium (18 μg once daily).
The probability of withdrawing from the study was 29% greater with tiotropium than with salmeterol and fluticasone (P=0.005).
Mortality was significantly lower for the combination treatment patients: 21 (3%) patients in this group died compared with 38 (6%) in the tiotropium group (P=0.032).
The exacerbation rates between the two groups were statistically indistinguishable, the researchers said. The modeled annual exacerbation rate was 1.28 per year in the salmeterol/fluticasone group and 1.32 in the tiotropium group (rate ratio: 0.967, 95% confidence interval: 0.836 to 1.119, P=0.656).
Although exacerbation rates were similar, there were differences in the treatment required. Oral corticosteroids were used more often to treat the tiotropium patients, whereas the combination patients required antibiotics more frequently, the researchers said.
Health status, measured by the St. George's Respiratory Questionnaire (SGRQ) total score, found a small but statistically significant beneficial effect at two years for the combination patients compared with those given tiotropium (difference: 2.1 units, 95% CI: 0.1 to 4.0; P=0.038).
At the end of the study, both treatments largely maintained the improvement in lung function (FEV1) achieved during the run-in period.
Although overall health status did not worsen, twice as many pneumonias were reported for the salmeterol/fluticasone patients than for those taking tiotropium (eight patients versus four, hazard ratio: 1.94, P=0.008).
The exact nature of these episodes and why they occurred is being evaluated further and remains to be determined, the researchers said.
This study raises several important questions, they noted: Why is there a difference in the nature of the exacerbations between the two treatments? What is the biological basis of the differential effect on exacerbations, and is it related to the difference in mortality between the two treatments?
Finally, the researchers said, there may be potential advantages from combining salmeterol/fluticasone and tiotropium, and this should be formally tested in adequately powered trials against other active comparators.
The two treatments achieved similar exacerbation rates with different mechanisms, as shown by the difference in the use of corticosteroids and antibiotics to treat exacerbation, and this resulted in different outcomes. "We believe that this has important implications for the choice of therapy in the management of COPD," they concluded.
This study was supported by GlaxoSmithKline, maker of salmeterol (Serevent) and fluticasone (Flovent).
Dr. Wedzicha reported receiving research funding from GlaxoSmithKline, Boehringer Ingelheim, and AstraZeneca, and also, honoraria from GlaxoSmithKline and Novartis, and lecture fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, and Novartis.
Co-author Gerry Hagan has been an employee of the sponsor, GlaxoSmithKline, since 1996 and holds stock options in different formats. Zainab Ansari, another co-author, was a full-time employee of GlaxoSmithKline from October 2002 to November 2006.
Primary source: American Journal of Respiratory and Critical Care MedicineSource reference:Wedzicha JA, et al "The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide" Am J Respir Crit Care Med 2008; 177: 19-26.
By Judith Groch
LONDON, Dec. 28 -- Combination drug therapy with salmeterol (Serevent), a long-acting inhaled bronchodilator, and fluticasone (Flovent) improved survival and led to fewer treatment withdrawals compared with single-drug therapy in severe COPD. A multicenter head-to-head study found a 52% reduction in the risk of all-cause mortality at any time during the study for the combo treatment compared with single-drug treatment, Jadwiga A. Wedzicha, M.D., of Royal Free & University College Medical School here, and colleagues reported in the first January issue of the American Journal of Critical Care Medicine Significantly, however, exacerbations, which are key drivers of morbidity and mortality, were similar for the two regimens, the researchers reported.
The study, Investigating New Standards for Prophylaxis in Reducing Exacerbations (INSPIRE), compared the relative efficacy of the combination treatment with monotherapy with the long-acting bronchodilator tiotropium (Spiriva).
In a two-year, double-blind, double-dummy parallel study, 1,323 patients (mean age, 64, post-bronchodilator FEV1, 39% predicted) were randomized to receive either the combination of salmeterol/ fluticasone (50/500 μg twice daily) or tiotropium (18 μg once daily).
The probability of withdrawing from the study was 29% greater with tiotropium than with salmeterol and fluticasone (P=0.005).
Mortality was significantly lower for the combination treatment patients: 21 (3%) patients in this group died compared with 38 (6%) in the tiotropium group (P=0.032).
The exacerbation rates between the two groups were statistically indistinguishable, the researchers said. The modeled annual exacerbation rate was 1.28 per year in the salmeterol/fluticasone group and 1.32 in the tiotropium group (rate ratio: 0.967, 95% confidence interval: 0.836 to 1.119, P=0.656).
Although exacerbation rates were similar, there were differences in the treatment required. Oral corticosteroids were used more often to treat the tiotropium patients, whereas the combination patients required antibiotics more frequently, the researchers said.
Health status, measured by the St. George's Respiratory Questionnaire (SGRQ) total score, found a small but statistically significant beneficial effect at two years for the combination patients compared with those given tiotropium (difference: 2.1 units, 95% CI: 0.1 to 4.0; P=0.038).
At the end of the study, both treatments largely maintained the improvement in lung function (FEV1) achieved during the run-in period.
Although overall health status did not worsen, twice as many pneumonias were reported for the salmeterol/fluticasone patients than for those taking tiotropium (eight patients versus four, hazard ratio: 1.94, P=0.008).
The exact nature of these episodes and why they occurred is being evaluated further and remains to be determined, the researchers said.
This study raises several important questions, they noted: Why is there a difference in the nature of the exacerbations between the two treatments? What is the biological basis of the differential effect on exacerbations, and is it related to the difference in mortality between the two treatments?
Finally, the researchers said, there may be potential advantages from combining salmeterol/fluticasone and tiotropium, and this should be formally tested in adequately powered trials against other active comparators.
The two treatments achieved similar exacerbation rates with different mechanisms, as shown by the difference in the use of corticosteroids and antibiotics to treat exacerbation, and this resulted in different outcomes. "We believe that this has important implications for the choice of therapy in the management of COPD," they concluded.
This study was supported by GlaxoSmithKline, maker of salmeterol (Serevent) and fluticasone (Flovent).
Dr. Wedzicha reported receiving research funding from GlaxoSmithKline, Boehringer Ingelheim, and AstraZeneca, and also, honoraria from GlaxoSmithKline and Novartis, and lecture fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, and Novartis.
Co-author Gerry Hagan has been an employee of the sponsor, GlaxoSmithKline, since 1996 and holds stock options in different formats. Zainab Ansari, another co-author, was a full-time employee of GlaxoSmithKline from October 2002 to November 2006.
Primary source: American Journal of Respiratory and Critical Care MedicineSource reference:Wedzicha JA, et al "The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide" Am J Respir Crit Care Med 2008; 177: 19-26.
Yoga Improves Sense of Well-Being, Reverses Changes in Metabolic Syndrome
By C. Vidyashankar
CHANNAI, India Dec 28 - Yoga induces a feeling of well-being in healthy people, and can reverse the clinical and biochemical changes associated with metabolic syndrome, according to results of studies from Sweden and India.
Dr. R.P. Agrawal, of the SP Medical College, Bikaner, India, and colleagues evaluated the beneficial effects of yoga and meditation in 101 adults with features of metabolic syndrome. In their randomized study, 55 subjects were assigned to 3 months of regular daily yoga, including standard postures, and Raja Yoga, a form of transcendental meditation, while the remaining received standard care.
Waist circumference, systolic blood pressure, fasting blood sugar, and triglycerides were significantly lower, and high density lipoprotein levels were higher in the yoga group as compared to controls, Dr. Agrawal's team reports in the December issue of Diabetes Research and Clinical Practice.
"Yoga and meditation have always been an essential part of life in the traditional system of treatment," Dr. R.P Agrawal and colleagues write. They attribute the effects to the redistribution of body fat, decreased arterial tone and peripheral resistance due to parasympathetic predominance, and increased sensitivity of beta cells of the pancreas.
In the second report, published on December 19 in BioMed Central Complementary and Alternative Medicine, Dr. Anette Kjellgren from the University of Karlstad, Sweden and her team evaluated the beneficial effects of yogic breathing exercises on healthy volunteers.
Fifty-five adults were advised to practice "Sudarshan Kriya," which involves cycles of slow normal and rapid breathing exercises. The exercises were practiced for an hour daily, six days a week for six weeks, while 48 controls were advised to relax in an armchair for 15 minutes daily.
At the end of the study period, feelings of anxiety, stress and depression were significantly decreased, and optimism was significantly increased, in the yoga group compared to controls, Dr. Kjellgren and colleagues report.
Yoga induces a "relaxation response" associated with reduced sympathetic nervous system activity and a feeling of well-being probably due to an increase in antioxidants and lower levels of cortisol, Dr. Kjellgren's team suggests.
Yoga not only helps in prevention of lifestyle diseases, but can also be "a powerful adjunct therapy when these diseases arise," co-author Dr. Faahri Saatiglou, from the University of Oslo, told Reuters Health. "We do not emphasize this point enough in our Western health care."
Diabetes Res Clin Pract 2007;78:e9-10.
By C. Vidyashankar
CHANNAI, India Dec 28 - Yoga induces a feeling of well-being in healthy people, and can reverse the clinical and biochemical changes associated with metabolic syndrome, according to results of studies from Sweden and India.
Dr. R.P. Agrawal, of the SP Medical College, Bikaner, India, and colleagues evaluated the beneficial effects of yoga and meditation in 101 adults with features of metabolic syndrome. In their randomized study, 55 subjects were assigned to 3 months of regular daily yoga, including standard postures, and Raja Yoga, a form of transcendental meditation, while the remaining received standard care.
Waist circumference, systolic blood pressure, fasting blood sugar, and triglycerides were significantly lower, and high density lipoprotein levels were higher in the yoga group as compared to controls, Dr. Agrawal's team reports in the December issue of Diabetes Research and Clinical Practice.
"Yoga and meditation have always been an essential part of life in the traditional system of treatment," Dr. R.P Agrawal and colleagues write. They attribute the effects to the redistribution of body fat, decreased arterial tone and peripheral resistance due to parasympathetic predominance, and increased sensitivity of beta cells of the pancreas.
In the second report, published on December 19 in BioMed Central Complementary and Alternative Medicine, Dr. Anette Kjellgren from the University of Karlstad, Sweden and her team evaluated the beneficial effects of yogic breathing exercises on healthy volunteers.
Fifty-five adults were advised to practice "Sudarshan Kriya," which involves cycles of slow normal and rapid breathing exercises. The exercises were practiced for an hour daily, six days a week for six weeks, while 48 controls were advised to relax in an armchair for 15 minutes daily.
At the end of the study period, feelings of anxiety, stress and depression were significantly decreased, and optimism was significantly increased, in the yoga group compared to controls, Dr. Kjellgren and colleagues report.
Yoga induces a "relaxation response" associated with reduced sympathetic nervous system activity and a feeling of well-being probably due to an increase in antioxidants and lower levels of cortisol, Dr. Kjellgren's team suggests.
Yoga not only helps in prevention of lifestyle diseases, but can also be "a powerful adjunct therapy when these diseases arise," co-author Dr. Faahri Saatiglou, from the University of Oslo, told Reuters Health. "We do not emphasize this point enough in our Western health care."
Diabetes Res Clin Pract 2007;78:e9-10.
Dutasteride/Tamsulosin May Be Helpful for Benign Prostatic Hyperplasia
Laurie Barclay
December 28, 2007 — In men with moderate to severe lower urinary tract symptoms (LUTS) and prostate enlargement (≥ 30 cc) from benign prostatic hyperplasia (BPH), combination therapy with tamsulosin and dutasteride provided significantly greater benefit vs tamsulosin or dutasteride monotherapy, according to the 2-year results from the Combination of Avodart and Tamsulosin (CombAT) study reported in the February issue of the Journal of Urology.
"The aim of the ongoing CombAT study is to investigate whether combination therapy with dutasteride and the alpha-blocker tamsulosin is more effective than either monotherapy alone for improving the symptoms and long-term clinical outcomes of AUR [acute urinary retention] and BPH related prostatic surgery in men with moderate to severe symptoms of BPH and a prostate volume of 30 cc or greater," write Claus G. Roehrborn, from the University of Texas Southwestern Medical Center in Dallas, Texas, and colleagues. "We report the results of analyses of the 2-year primary and secondary end points of LUTS, Qmax [peak urinary flow] and prostate volume, and further analyses of efficacy data as well as safety and tolerability outcomes."
In this ongoing, multicenter, double-blind, parallel group study, men 50 years or older with a clinical diagnosis of BPH and LUTS were randomized to receive 0.5 mg of dutasteride, 0.4 mg of tamsulosin, or the combination once daily for 4 years. Inclusion criteria were International Prostate Symptom Score (IPSS) of 12 points or greater, prostate volume 30 cc or greater, total serum prostate-specific antigen (PSA) of 1.5 ng/mL or greater to 10 ng/mL or less, and peak urinary flow greater than 5 to 15 mL per second or less with a minimum voided volume of 125 mL or greater.
LUTS were evaluated every 3 months, and peak urinary flow was evaluated every 6 months. The main outcome measure at 2 years was the change from baseline in IPSS.
Compared with monotherapy, combination therapy resulted in significantly greater improvements in LUTS vs dutasteride from month 3 and tamsulosin from month 9, and in BPH-related health status from months 3 and 12, respectively. From month 6, combination therapy was associated with a significantly greater improvement from baseline in peak urinary flow vs monotherapy dutasteride or tamsulosin monotherapies.
Compared with monotherapies, combination therapy was associated with a significant increase in drug-related adverse events. However, most of these did not necessitate stopping treatment.
"In men with moderate to severe lower urinary tract symptoms and prostate enlargement (≥ 30 cc) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy," the study authors write.
A limitation of the CombAT study was the lack of a double placebo group, which could potentially exaggerate symptom response.
"Data from the remaining 2 years of the CombAT study will provide further information on the pattern of symptoms and long-term outcomes (AUR and the need for BPH related surgery) associated with combination therapy vs tamsulosin and dutasteride monotherapies," the study authors conclude.
GlaxoSmithKline supported this study. Some of the authors have disclosed various financial relationships with GlaxoSmithKline, Pfizer, Astellas, Merck, Indevus, Eli Lilly, and Bayer.
In an accompanying editorial comment, Steven A. Kaplan, from Weill Cornell Medical College of Cornell University in New York City, notes that one must be cautious not to overinterpret these findings. Nonetheless, he describes CombAT as "an important contribution to our evolving understanding of the management of LUTS."
"The 5-ARIs [5-alpha-reductase inhibitor] and specifically in this study dutasteride are widely accepted as the backbone of therapy because of their unparalleled [effect] on disease management and they are also highly effective for relieving symptoms in select patients," Dr. Kaplan writes. "The alpha-blockers probably do not work as effectively in large prostates as they do in smaller prostates. What remains indisputable is that prostate size and symptom type, ie storage vs voiding at baseline, will drive therapeutic choices and optimize outcomes."
J Urol. 2008;179:616-621. Published online December 19, 2007.
Laurie Barclay
December 28, 2007 — In men with moderate to severe lower urinary tract symptoms (LUTS) and prostate enlargement (≥ 30 cc) from benign prostatic hyperplasia (BPH), combination therapy with tamsulosin and dutasteride provided significantly greater benefit vs tamsulosin or dutasteride monotherapy, according to the 2-year results from the Combination of Avodart and Tamsulosin (CombAT) study reported in the February issue of the Journal of Urology.
"The aim of the ongoing CombAT study is to investigate whether combination therapy with dutasteride and the alpha-blocker tamsulosin is more effective than either monotherapy alone for improving the symptoms and long-term clinical outcomes of AUR [acute urinary retention] and BPH related prostatic surgery in men with moderate to severe symptoms of BPH and a prostate volume of 30 cc or greater," write Claus G. Roehrborn, from the University of Texas Southwestern Medical Center in Dallas, Texas, and colleagues. "We report the results of analyses of the 2-year primary and secondary end points of LUTS, Qmax [peak urinary flow] and prostate volume, and further analyses of efficacy data as well as safety and tolerability outcomes."
In this ongoing, multicenter, double-blind, parallel group study, men 50 years or older with a clinical diagnosis of BPH and LUTS were randomized to receive 0.5 mg of dutasteride, 0.4 mg of tamsulosin, or the combination once daily for 4 years. Inclusion criteria were International Prostate Symptom Score (IPSS) of 12 points or greater, prostate volume 30 cc or greater, total serum prostate-specific antigen (PSA) of 1.5 ng/mL or greater to 10 ng/mL or less, and peak urinary flow greater than 5 to 15 mL per second or less with a minimum voided volume of 125 mL or greater.
LUTS were evaluated every 3 months, and peak urinary flow was evaluated every 6 months. The main outcome measure at 2 years was the change from baseline in IPSS.
Compared with monotherapy, combination therapy resulted in significantly greater improvements in LUTS vs dutasteride from month 3 and tamsulosin from month 9, and in BPH-related health status from months 3 and 12, respectively. From month 6, combination therapy was associated with a significantly greater improvement from baseline in peak urinary flow vs monotherapy dutasteride or tamsulosin monotherapies.
Compared with monotherapies, combination therapy was associated with a significant increase in drug-related adverse events. However, most of these did not necessitate stopping treatment.
"In men with moderate to severe lower urinary tract symptoms and prostate enlargement (≥ 30 cc) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy," the study authors write.
A limitation of the CombAT study was the lack of a double placebo group, which could potentially exaggerate symptom response.
"Data from the remaining 2 years of the CombAT study will provide further information on the pattern of symptoms and long-term outcomes (AUR and the need for BPH related surgery) associated with combination therapy vs tamsulosin and dutasteride monotherapies," the study authors conclude.
GlaxoSmithKline supported this study. Some of the authors have disclosed various financial relationships with GlaxoSmithKline, Pfizer, Astellas, Merck, Indevus, Eli Lilly, and Bayer.
In an accompanying editorial comment, Steven A. Kaplan, from Weill Cornell Medical College of Cornell University in New York City, notes that one must be cautious not to overinterpret these findings. Nonetheless, he describes CombAT as "an important contribution to our evolving understanding of the management of LUTS."
"The 5-ARIs [5-alpha-reductase inhibitor] and specifically in this study dutasteride are widely accepted as the backbone of therapy because of their unparalleled [effect] on disease management and they are also highly effective for relieving symptoms in select patients," Dr. Kaplan writes. "The alpha-blockers probably do not work as effectively in large prostates as they do in smaller prostates. What remains indisputable is that prostate size and symptom type, ie storage vs voiding at baseline, will drive therapeutic choices and optimize outcomes."
J Urol. 2008;179:616-621. Published online December 19, 2007.
Practice Guidelines Issued for Screening, Diagnosing, and Treating Diabetes
Laurie Barclay
December 28, 2007 — The American Diabetes Association (ADA) has issued practice guidelines for screening, diagnostic, and therapeutic interventions that are known or believed to improve health outcomes of patients with diabetes. An executive summary published in the January issue of Diabetes Care provides a detailed description of each of the ADA practice recommendations, a grading system developed by the ADA that uses A, B, C, or E to indicate the level of evidence supporting each recommendation, and suggested targets for most patients with diabetes.
"These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care," the guidelines authors write. "While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed."
Specific topic areas covered include diagnosis of diabetes, testing for prediabetes and diabetes, testing for type 2 diabetes in children, detection and diagnosis of gestational diabetes mellitus, prevention and delay of type 2 diabetes, self-monitoring of blood glucose levels, hemoglobin A1c (A1C) levels, glycemic goals, medical nutrition therapy (MNT), diabetes self-management education (DSME), physical activity, psychosocial assessment and care, hypoglycemia, immunization, hypertension and blood pressure control, and dyslipidemia and lipid management.
Also covered are use of antiplatelet agents, smoking cessation, coronary heart disease screening and treatment, nephropathy screening and treatment, retinopathy screening and treatment, neuropathy screening and treatment, foot care, special issues in treating children and adolescents, preconception care, special issues in treating older adults, diabetes care in the hospital (including goals for blood glucose levels), diabetes care in the school and day care setting, diabetes care at diabetes camps, diabetes management in correctional institutions, emergency and disaster preparedness, hypoglycemia and employment/licensure, and third-party reimbursement for diabetes care, self-management education, and supplies.
Some of the specific recommendations are as follows:
To diagnose diabetes in children and nonpregnant adults, fasting plasma glucose (FPG) is the preferred test, and use of A1C levels to diagnose diabetes is not currently recommended (E).
Screening for prediabetes and type 2 diabetes in asymptomatic people should be considered in adults who are overweight or obese (body mass index [BMI] ≥25 kg/m2) with at least 1 more additional risk factor. Otherwise, testing should begin at age 45 years (B), and if results are normal, testing should be repeated at least at 3-year intervals (E).
Either an FPG test or 2-hour oral glucose tolerance test (OGTT; 75-g glucose load), or both, is appropriate (B) to test for prediabetes or diabetes, and an OGTT may be considered in patients with impaired fasting glucose (IFG) to better define the risk of diabetes (E).
Individuals found to have prediabetes should be evaluated and treated, if appropriate, for other cardiovascular risk factors (B).
To prevent or delay onset of diabetes, patients with impaired glucose tolerance (IGT; A) or IFG (E) should be advised to lose 5% to 10% of body weight and to increase physical activity to at least 150 minutes per week of moderate activity such as walking. Follow-up counseling seems to improve the likelihood of success (B). Because of the potential cost savings associated with diabetes prevention, third-party payors should cover counseling (E).
Metformin therapy should also be considered in patients who are at very high risk for diabetes, based on combined IFG and IGT plus other risk factors, and who are obese and younger than 60 years of age (E).
Individuals with prediabetes should be monitored every year for the development of diabetes. (E).
Because lowering A1C levels to an average of about 7% has been shown to reduce microvascular and neuropathic complications of diabetes and, possibly, macrovascular disease, the target A1c goal for nonpregnant adults is generally less than 7% (A).
For selected individual patients, the A1C goal is as close to normal (< 6%) as possible without significant hypoglycemia (B), in light of epidemiologic studies showing a small but incremental benefit to lowering A1C from 7% into the normal range.
For children, patients with a history of severe hypoglycemia, those with limited life expectancies, individuals with comorbid conditions, and those with long duration of diabetes and minimal or stable microvascular complications, less stringent A1C goals may be appropriate (E).
Individuals with prediabetes or diabetes should receive individualized MNT as needed to achieve treatment goals, ideally by a registered dietitian who is knowledgeable about diabetes MNT (B). This should be covered by insurance and other payors (E).
Specific components of MNT should include management of energy balance, overweight, and obesity with diet, physical activity, and behavior modification (B); primary prevention of diabetes among individuals at high risk of developing type 2 diabetes (A); promoting fiber and whole-grain intake meeting US Department of Agriculture recommendations (B); controlling dietary fat intake by limiting saturated fat intake to less than 7% of total calories (A) and minimizing trans fat intake (E); and managing carbohydrate intake.
Monitoring carbohydrate intake is a key strategy in achieving glycemic control, whether by carbohydrate counting, exchanges, or experience-based estimation (A). For patients with diabetes, glycemic index and glycemic load use may modestly improve glycemic control vs that observed when considering only total carbohydrate (B).
DSME should be offered to patients with diabetes at the time of diagnosis and as needed thereafter (B), with the goal of changing self-management behavior (E) and addressing psychosocial issues (C). Third-party payors should reimburse for DSME (E).
People with diabetes should perform at least 150 minutes per week of moderate-intensity aerobic physical activity (50% - 70% of maximum heart rate; [A]), and unless there are contraindications, those with type 2 diabetes should perform resistance training 3 times per week (A).
"People with diabetes should be individually considered for employment based on the requirements of the specific job and the individual's medical condition, treatment regimen, and medical history (E)," the guidelines authors conclude. "Patients and practitioners should have access to all classes of antidiabetic medications, equipment, and supplies without undue controls (E). MNT and DSME should be covered by insurance and other payors (E)."
Diabetes Care. 2008;31(suppl 1):S5-S11.
Laurie Barclay
December 28, 2007 — The American Diabetes Association (ADA) has issued practice guidelines for screening, diagnostic, and therapeutic interventions that are known or believed to improve health outcomes of patients with diabetes. An executive summary published in the January issue of Diabetes Care provides a detailed description of each of the ADA practice recommendations, a grading system developed by the ADA that uses A, B, C, or E to indicate the level of evidence supporting each recommendation, and suggested targets for most patients with diabetes.
"These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care," the guidelines authors write. "While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed."
Specific topic areas covered include diagnosis of diabetes, testing for prediabetes and diabetes, testing for type 2 diabetes in children, detection and diagnosis of gestational diabetes mellitus, prevention and delay of type 2 diabetes, self-monitoring of blood glucose levels, hemoglobin A1c (A1C) levels, glycemic goals, medical nutrition therapy (MNT), diabetes self-management education (DSME), physical activity, psychosocial assessment and care, hypoglycemia, immunization, hypertension and blood pressure control, and dyslipidemia and lipid management.
Also covered are use of antiplatelet agents, smoking cessation, coronary heart disease screening and treatment, nephropathy screening and treatment, retinopathy screening and treatment, neuropathy screening and treatment, foot care, special issues in treating children and adolescents, preconception care, special issues in treating older adults, diabetes care in the hospital (including goals for blood glucose levels), diabetes care in the school and day care setting, diabetes care at diabetes camps, diabetes management in correctional institutions, emergency and disaster preparedness, hypoglycemia and employment/licensure, and third-party reimbursement for diabetes care, self-management education, and supplies.
Some of the specific recommendations are as follows:
To diagnose diabetes in children and nonpregnant adults, fasting plasma glucose (FPG) is the preferred test, and use of A1C levels to diagnose diabetes is not currently recommended (E).
Screening for prediabetes and type 2 diabetes in asymptomatic people should be considered in adults who are overweight or obese (body mass index [BMI] ≥25 kg/m2) with at least 1 more additional risk factor. Otherwise, testing should begin at age 45 years (B), and if results are normal, testing should be repeated at least at 3-year intervals (E).
Either an FPG test or 2-hour oral glucose tolerance test (OGTT; 75-g glucose load), or both, is appropriate (B) to test for prediabetes or diabetes, and an OGTT may be considered in patients with impaired fasting glucose (IFG) to better define the risk of diabetes (E).
Individuals found to have prediabetes should be evaluated and treated, if appropriate, for other cardiovascular risk factors (B).
To prevent or delay onset of diabetes, patients with impaired glucose tolerance (IGT; A) or IFG (E) should be advised to lose 5% to 10% of body weight and to increase physical activity to at least 150 minutes per week of moderate activity such as walking. Follow-up counseling seems to improve the likelihood of success (B). Because of the potential cost savings associated with diabetes prevention, third-party payors should cover counseling (E).
Metformin therapy should also be considered in patients who are at very high risk for diabetes, based on combined IFG and IGT plus other risk factors, and who are obese and younger than 60 years of age (E).
Individuals with prediabetes should be monitored every year for the development of diabetes. (E).
Because lowering A1C levels to an average of about 7% has been shown to reduce microvascular and neuropathic complications of diabetes and, possibly, macrovascular disease, the target A1c goal for nonpregnant adults is generally less than 7% (A).
For selected individual patients, the A1C goal is as close to normal (< 6%) as possible without significant hypoglycemia (B), in light of epidemiologic studies showing a small but incremental benefit to lowering A1C from 7% into the normal range.
For children, patients with a history of severe hypoglycemia, those with limited life expectancies, individuals with comorbid conditions, and those with long duration of diabetes and minimal or stable microvascular complications, less stringent A1C goals may be appropriate (E).
Individuals with prediabetes or diabetes should receive individualized MNT as needed to achieve treatment goals, ideally by a registered dietitian who is knowledgeable about diabetes MNT (B). This should be covered by insurance and other payors (E).
Specific components of MNT should include management of energy balance, overweight, and obesity with diet, physical activity, and behavior modification (B); primary prevention of diabetes among individuals at high risk of developing type 2 diabetes (A); promoting fiber and whole-grain intake meeting US Department of Agriculture recommendations (B); controlling dietary fat intake by limiting saturated fat intake to less than 7% of total calories (A) and minimizing trans fat intake (E); and managing carbohydrate intake.
Monitoring carbohydrate intake is a key strategy in achieving glycemic control, whether by carbohydrate counting, exchanges, or experience-based estimation (A). For patients with diabetes, glycemic index and glycemic load use may modestly improve glycemic control vs that observed when considering only total carbohydrate (B).
DSME should be offered to patients with diabetes at the time of diagnosis and as needed thereafter (B), with the goal of changing self-management behavior (E) and addressing psychosocial issues (C). Third-party payors should reimburse for DSME (E).
People with diabetes should perform at least 150 minutes per week of moderate-intensity aerobic physical activity (50% - 70% of maximum heart rate; [A]), and unless there are contraindications, those with type 2 diabetes should perform resistance training 3 times per week (A).
"People with diabetes should be individually considered for employment based on the requirements of the specific job and the individual's medical condition, treatment regimen, and medical history (E)," the guidelines authors conclude. "Patients and practitioners should have access to all classes of antidiabetic medications, equipment, and supplies without undue controls (E). MNT and DSME should be covered by insurance and other payors (E)."
Diabetes Care. 2008;31(suppl 1):S5-S11.
Explain a Medical Error? Sure. Apologize Too?
By SANDEEP JAUHAR
One morning not long ago, I got a call from the emergency room at my hospital. A young man — an intern, in fact, who had been on rounds that morning — had been admitted with chest pains. Could I come to evaluate him?
He was 30, a Pakistani man with a long face and a disconnected look, which I attributed to anxiety. I asked him about the pain. It had started after dinner the night before, lasting about 10 minutes. He had slept comfortably, but the pain recurred while he was walking to the bus stop that morning, persisting almost an hour. It was a dense pressure in the center of his chest. To be on the safe side, he had decided to leave rounds and come to the E.R.
His blood tests were normal, as was his first electrocardiogram. He had none of the traditional risk factors for heart disease. I suspected he was suffering from acute pericarditis, a usually benign inflammation of the membrane around the heart often treated with over-the-counter anti-inflammatory drugs. Characteristic of pericarditis, the pain worsened when he took a deep breath. I told him that if blood tests in six hours were normal, we would send him home. I joked that there were easier ways to get out of internship duty.
Later that morning, I got a call from an E.R. physician informing me that my patient’s pain had resolved completely after he took ibuprofen, further confirming the diagnosis of pericarditis. For a moment I considered sending him home right then, but I decided to wait until the next set of blood tests was complete.
Just before leaving the hospital that evening, I ran into a physicians’ assistant. He told me that my patient’s subsequent blood tests showed evidence of minor cardiac muscle damage. Though surprised, I quickly explained that the problem was probably myopericarditis, where inflammation of the surrounding membrane can partially involve the heart muscle.
He asked me whether the young doctor should have an angiogram to rule out artery blockages. It was late; I told him that any work-up could wait until morning. I assured him that a 30-year-old with no risk factors did not have coronary artery disease. I told him to draw more enzymes and to order a cardiac ultrasound for the morning, and to call me at home if there were problems.
My patient had chest pains through the night. Doctors who were called to see him attributed them to myopericarditis, the diagnosis written in the chart. Further blood tests showed evidence of continuing heart muscle injury. An EKG the following morning showed nonspecific signs consistent with a heart attack. Though I still doubted that he had coronary disease, I reluctantly sent him to the cardiac catheterization lab for an angiogram.
I received a call about an hour later asking me to come over to the lab. When I arrived, the angiogram was playing on a computer screen. It showed a complete blockage of the left anterior descending artery, the so-called widow-maker lesion. The artery looked like a lobster tail, unnaturally terminating after several centimeters. Within minutes, the blockage was opened with a balloon and a stent.
Afterward, in the control room, heat rose to my face as colleagues wandered in to inquire about what was going on. “How could we have missed this?” I asked aloud. I was well aware of the disturbing prevalence of heart disease in South Asians, whose risk is up to four times that of other ethnic groups. I knew that heart attacks in this population often occurred in men under 40, who often do not exhibit classic coronary risk factors. I knew all this, but somehow my mind had suffered a block.
“Don’t beat yourself up,” a colleague said sympathetically. “Every doctor I know would have done the same thing.” Another told me that it was his policy to “cath” almost anyone who came to the E.R. complaining of chest pains. In his opinion, the risks posed by routine angiograms were much less than that of a missed heart attack.
What now? I knew I had to explain myself, but how much should I say? Like all doctors, I had made errors before, but never one this big — and in my own specialty, too. Should I just tell my patient the facts? Should I apologize?
Most doctors are afraid to take responsibility for medical errors. We are acutely aware of the potential hazards — legal and professional — of taking ownership of a mistake. But studies have shown that physicians’ apologies do not necessarily increase malpractice lawsuits. In fact, they may protect against litigation. Seventeen states have enacted legislation encouraging such apologies, some even making physicians’ expressions of remorse inadmissible in court.
It was not always this way. Hospital legal departments routinely used to advise doctors never to admit responsibility for an error.
During my internship orientation nearly a decade ago, a lawyer for the hospital said that at some point in our careers every one of us would likely be sued. The lawyer offered some advice: document your decision-making; document when a patient refuses treatment; never admit wrongdoing; never talk to an opposing attorney; and, finally, be nice to your patients. Doctors who were nice to their patients were rarely sued, even in cases of egregious malpractice.
I couldn’t bring myself to talk to my patient in the cath lab, while everyone was watching, so I decided to wait until he got to the recovery room, where it was more private.
I found him there lying on a stretcher. The pain in his chest was gone, he happily informed me. However, the groin, where the catheter had been inserted, now hurt. “They substituted one pain for another,” he said, laughing.
I grasped the rails of the gurney. “I thought you had pericarditis,” I said carefully. “I was obviously wrong. I’m sorry.”
He seemed embarrassed. “No, no, please, the past is finished,” he replied. “I am more interested in the future.”
He asked about his prognosis. I told him that I thought it was good, though he would have to be on medications for the rest of his life. He nodded, looking disappointed.
A few days later, just before he was to be discharged, I stopped by his room. I asked him with whom he was going to follow up. He told me that he had been given the name of another cardiologist but that he had decided to go with me. “You have been terrific,” he said. “Thank you.”
I nodded silently, feeling empty. “You are much too generous,” I said.
Sandeep Jauhar is the author of a memoir, “Intern: A Doctor’s Initiation,” being published this month by Farrar, Straus & Giroux.
By SANDEEP JAUHAR
One morning not long ago, I got a call from the emergency room at my hospital. A young man — an intern, in fact, who had been on rounds that morning — had been admitted with chest pains. Could I come to evaluate him?
He was 30, a Pakistani man with a long face and a disconnected look, which I attributed to anxiety. I asked him about the pain. It had started after dinner the night before, lasting about 10 minutes. He had slept comfortably, but the pain recurred while he was walking to the bus stop that morning, persisting almost an hour. It was a dense pressure in the center of his chest. To be on the safe side, he had decided to leave rounds and come to the E.R.
His blood tests were normal, as was his first electrocardiogram. He had none of the traditional risk factors for heart disease. I suspected he was suffering from acute pericarditis, a usually benign inflammation of the membrane around the heart often treated with over-the-counter anti-inflammatory drugs. Characteristic of pericarditis, the pain worsened when he took a deep breath. I told him that if blood tests in six hours were normal, we would send him home. I joked that there were easier ways to get out of internship duty.
Later that morning, I got a call from an E.R. physician informing me that my patient’s pain had resolved completely after he took ibuprofen, further confirming the diagnosis of pericarditis. For a moment I considered sending him home right then, but I decided to wait until the next set of blood tests was complete.
Just before leaving the hospital that evening, I ran into a physicians’ assistant. He told me that my patient’s subsequent blood tests showed evidence of minor cardiac muscle damage. Though surprised, I quickly explained that the problem was probably myopericarditis, where inflammation of the surrounding membrane can partially involve the heart muscle.
He asked me whether the young doctor should have an angiogram to rule out artery blockages. It was late; I told him that any work-up could wait until morning. I assured him that a 30-year-old with no risk factors did not have coronary artery disease. I told him to draw more enzymes and to order a cardiac ultrasound for the morning, and to call me at home if there were problems.
My patient had chest pains through the night. Doctors who were called to see him attributed them to myopericarditis, the diagnosis written in the chart. Further blood tests showed evidence of continuing heart muscle injury. An EKG the following morning showed nonspecific signs consistent with a heart attack. Though I still doubted that he had coronary disease, I reluctantly sent him to the cardiac catheterization lab for an angiogram.
I received a call about an hour later asking me to come over to the lab. When I arrived, the angiogram was playing on a computer screen. It showed a complete blockage of the left anterior descending artery, the so-called widow-maker lesion. The artery looked like a lobster tail, unnaturally terminating after several centimeters. Within minutes, the blockage was opened with a balloon and a stent.
Afterward, in the control room, heat rose to my face as colleagues wandered in to inquire about what was going on. “How could we have missed this?” I asked aloud. I was well aware of the disturbing prevalence of heart disease in South Asians, whose risk is up to four times that of other ethnic groups. I knew that heart attacks in this population often occurred in men under 40, who often do not exhibit classic coronary risk factors. I knew all this, but somehow my mind had suffered a block.
“Don’t beat yourself up,” a colleague said sympathetically. “Every doctor I know would have done the same thing.” Another told me that it was his policy to “cath” almost anyone who came to the E.R. complaining of chest pains. In his opinion, the risks posed by routine angiograms were much less than that of a missed heart attack.
What now? I knew I had to explain myself, but how much should I say? Like all doctors, I had made errors before, but never one this big — and in my own specialty, too. Should I just tell my patient the facts? Should I apologize?
Most doctors are afraid to take responsibility for medical errors. We are acutely aware of the potential hazards — legal and professional — of taking ownership of a mistake. But studies have shown that physicians’ apologies do not necessarily increase malpractice lawsuits. In fact, they may protect against litigation. Seventeen states have enacted legislation encouraging such apologies, some even making physicians’ expressions of remorse inadmissible in court.
It was not always this way. Hospital legal departments routinely used to advise doctors never to admit responsibility for an error.
During my internship orientation nearly a decade ago, a lawyer for the hospital said that at some point in our careers every one of us would likely be sued. The lawyer offered some advice: document your decision-making; document when a patient refuses treatment; never admit wrongdoing; never talk to an opposing attorney; and, finally, be nice to your patients. Doctors who were nice to their patients were rarely sued, even in cases of egregious malpractice.
I couldn’t bring myself to talk to my patient in the cath lab, while everyone was watching, so I decided to wait until he got to the recovery room, where it was more private.
I found him there lying on a stretcher. The pain in his chest was gone, he happily informed me. However, the groin, where the catheter had been inserted, now hurt. “They substituted one pain for another,” he said, laughing.
I grasped the rails of the gurney. “I thought you had pericarditis,” I said carefully. “I was obviously wrong. I’m sorry.”
He seemed embarrassed. “No, no, please, the past is finished,” he replied. “I am more interested in the future.”
He asked about his prognosis. I told him that I thought it was good, though he would have to be on medications for the rest of his life. He nodded, looking disappointed.
A few days later, just before he was to be discharged, I stopped by his room. I asked him with whom he was going to follow up. He told me that he had been given the name of another cardiologist but that he had decided to go with me. “You have been terrific,” he said. “Thank you.”
I nodded silently, feeling empty. “You are much too generous,” I said.
Sandeep Jauhar is the author of a memoir, “Intern: A Doctor’s Initiation,” being published this month by Farrar, Straus & Giroux.
Cancer patients, doctors talk little of emotions
By Amy Norton
People with advanced cancer may suffer substantial emotional distress, but relatively few may be discussing it with their doctors, new research suggests.
In a study that recorded conversations between 270 cancer patients and their oncologists, researchers found that patients broached the topic of emotional concerns only about one-third of the time. And when they did open the door, their doctors often failed to encourage a discussion.
The findings suggest that cancer specialists need more training in how to respond to patients' emotional needs, according to the researchers, led by Dr. Kathryn I. Pollak of Duke University Medical Center in Durham, North Carolina.
They report the findings in the Journal of Clinical Oncology.
Of 398 doctor-patient conversations the researchers recorded, 37 percent featured a moment of what they call an "empathic opportunity," where a patient opens up about his emotions, either directly or in more subtle ways.
The doctor can encourage the patient to go on in any number of ways -- by asking questions, or simply expressing empathy and understanding. But in this study, doctors did that only 22 percent of the time.
More often, they cut the discussion short with statements like, "Give us time. We are getting there."
The findings do not mean, however, that doctors don't care about their patients' emotional well-being, according to Pollak.
"Cancer patients should know their oncologists care deeply about them," she told Reuters Health. "However, oncologists don't always know how to verbalize that they care."
In this study, younger doctors tended to encourage discussion more often than older doctors did, and female patients were more likely to open up about their emotions when they saw a female oncologist. Male patients talked about their emotions less often than female patients did, regardless of the sex of their doctor.
Communication skills are now commonly taught in medical school and residency programs, but many practicing oncologists have never been trained to respond to patients' emotional concerns with empathy, according to the researchers.
The current findings, they write, suggest that oncologists "may need more training to recognize emotions and to learn how to respond to patient concerns."
Patients may also be able to aid communication by being more direct about their emotions, Pollak suggested.
As an example, she said that, instead of saying something vague like "I'm not sure what I should do," a patient could say something specific and hard to misinterpret, like "I am really depressed. What should I do about that?"
SOURCE: Journal of Clinical Oncology, December 20, 2007.
By Amy Norton
People with advanced cancer may suffer substantial emotional distress, but relatively few may be discussing it with their doctors, new research suggests.
In a study that recorded conversations between 270 cancer patients and their oncologists, researchers found that patients broached the topic of emotional concerns only about one-third of the time. And when they did open the door, their doctors often failed to encourage a discussion.
The findings suggest that cancer specialists need more training in how to respond to patients' emotional needs, according to the researchers, led by Dr. Kathryn I. Pollak of Duke University Medical Center in Durham, North Carolina.
They report the findings in the Journal of Clinical Oncology.
Of 398 doctor-patient conversations the researchers recorded, 37 percent featured a moment of what they call an "empathic opportunity," where a patient opens up about his emotions, either directly or in more subtle ways.
The doctor can encourage the patient to go on in any number of ways -- by asking questions, or simply expressing empathy and understanding. But in this study, doctors did that only 22 percent of the time.
More often, they cut the discussion short with statements like, "Give us time. We are getting there."
The findings do not mean, however, that doctors don't care about their patients' emotional well-being, according to Pollak.
"Cancer patients should know their oncologists care deeply about them," she told Reuters Health. "However, oncologists don't always know how to verbalize that they care."
In this study, younger doctors tended to encourage discussion more often than older doctors did, and female patients were more likely to open up about their emotions when they saw a female oncologist. Male patients talked about their emotions less often than female patients did, regardless of the sex of their doctor.
Communication skills are now commonly taught in medical school and residency programs, but many practicing oncologists have never been trained to respond to patients' emotional concerns with empathy, according to the researchers.
The current findings, they write, suggest that oncologists "may need more training to recognize emotions and to learn how to respond to patient concerns."
Patients may also be able to aid communication by being more direct about their emotions, Pollak suggested.
As an example, she said that, instead of saying something vague like "I'm not sure what I should do," a patient could say something specific and hard to misinterpret, like "I am really depressed. What should I do about that?"
SOURCE: Journal of Clinical Oncology, December 20, 2007.
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