Mary Ann Moon

Delays in reperfusion were substantially reduced for patients with ST-segment elevation myocardial infarction after a statewide program was introduced in North Carolina.

The results of the program were announced on Nov. 4 at the annual scientific sessions of the American Heart Association in Orlando and simultaneously published online (JAMA 2007 Nov. 4 [Epubdoi:10.1001/jama.298.20.joc70124]).

Described as “one of the largest and most extensive regional systems … for the reperfusion of STEMI developed in the United States,” the program was modeled on systems for general trauma care. The program streamlined protocols and coordinated emergency medical services, hospital emergency departments, catheterization labs, and interhospital transfer, according to Dr. Christopher B. Granger of the division of cardiology at Duke University, Durham, N.C., and his associates.

After this program was instituted, the proportion of PCI patients who achieved door-to-device times of 90 minutes or less increased from 57% to 72%, and the median interval decreased from 85 minutes to 74 minutes, the researchers noted.

For patients who presented to hospitals that didn't perform PCI and therefore had to be transferred, the median door-to-device time dropped from 165 minutes to 128 minutes. Median door-in to door-out times decreased from 120 minutes to 71 minutes, “one of the greatest reductions observed in the study,” Dr. Granger and his associates said.

For patients undergoing fibrinolysis, the proportion who achieved door-to-needle times of less than 30 minutes rose from 35% to 52%, and the median interval decreased from 35 minutes to 29 minutes.

The program shaved times by eliminating waits for a cardiology consultation and by having an on-call interventional cardiologist identified at all times.

The emergency physician or paramedic could activate the nearest catheterization laboratory at any hour on any day of the week with a single phone call. Emergency department physicians or medical technicians were allowed to start treatment without waits for a cardiology consultation.

The on-call interventional cardiologist eliminated delays that result when “trying to determine which cardiologist from several competing groups would intervene.” Time to treatment was trimmed in remote areas by encouraging the use of local ambulances rather than helicopters or mobile critical care units. Other strategies included leaving patients “on the stretcher” when appropriate for more rapid evaluation and transfer.

Since STEMI “was a relatively infrequent event for most emergency personnel” to encounter, the program established a specific reperfusion plan that would cover most patients and would sidestep clinician delays that resulted from “indecision” and the need to develop individualized treatment plans.

ICU nurses staffed catheterization labs on an emergency basis, when night and weekend coverage by the usual staff couldn't be arranged. Certain procedures conducted by paramedics and medical technicians were modified to save time. For example, use of intravenous drips such as heparin or nitroglycerin were minimized because substantial delays were associated with establishing and changing infusion lines.

Additionally, the program addressed the limitations of regions with severe restrictions on available equipment and personnel. In resource-poor regions, intermediate-level emergency medical technicians were allowed to perform electrocardiograms. Paramedics were sometimes allowed to interpret ECGs, sometimes with the aid of computer algorithms or via electronic transmission to a physician.

ELSEVIER GLOBAL MEDICAL NEWS

Delays in reperfusion were substantially reduced for patients with ST-segment elevation myocardial infarction after a statewide program was introduced in North Carolina.

The results of the program were announced on Nov. 4 at the annual scientific sessions of the American Heart Association in Orlando and simultaneously published online (JAMA 2007 Nov. 4 [Epubdoi:10.1001/jama.298.20.joc70124]).

Described as “one of the largest and most extensive regional systems … for the reperfusion of STEMI developed in the United States,” the program was modeled on systems for general trauma care. The program streamlined protocols and coordinated emergency medical services, hospital emergency departments, catheterization labs, and interhospital transfer, according to Dr. Christopher B. Granger of the division of cardiology at Duke University, Durham, N.C., and his associates.

After this program was instituted, the proportion of PCI patients who achieved door-to-device times of 90 minutes or less increased from 57% to 72%, and the median interval decreased from 85 minutes to 74 minutes, the researchers noted.

For patients who presented to hospitals that didn't perform PCI and therefore had to be transferred, the median door-to-device time dropped from 165 minutes to 128 minutes. Median door-in to door-out times decreased from 120 minutes to 71 minutes, “one of the greatest reductions observed in the study,” Dr. Granger and his associates said.

For patients undergoing fibrinolysis, the proportion who achieved door-to-needle times of less than 30 minutes rose from 35% to 52%, and the median interval decreased from 35 minutes to 29 minutes.

The program shaved times by eliminating waits for a cardiology consultation and by having an on-call interventional cardiologist identified at all times.

The emergency physician or paramedic could activate the nearest catheterization laboratory at any hour on any day of the week with a single phone call. Emergency department physicians or medical technicians were allowed to start treatment without waits for a cardiology consultation.

The on-call interventional cardiologist eliminated delays that result when “trying to determine which cardiologist from several competing groups would intervene.” Time to treatment was trimmed in remote areas by encouraging the use of local ambulances rather than helicopters or mobile critical care units. Other strategies included leaving patients “on the stretcher” when appropriate for more rapid evaluation and transfer.

Since STEMI “was a relatively infrequent event for most emergency personnel” to encounter, the program established a specific reperfusion plan that would cover most patients and would sidestep clinician delays that resulted from “indecision” and the need to develop individualized treatment plans.

ICU nurses staffed catheterization labs on an emergency basis, when night and weekend coverage by the usual staff couldn't be arranged. Certain procedures conducted by paramedics and medical technicians were modified to save time. For example, use of intravenous drips such as heparin or nitroglycerin were minimized because substantial delays were associated with establishing and changing infusion lines.

Additionally, the program addressed the limitations of regions with severe restrictions on available equipment and personnel. In resource-poor regions, intermediate-level emergency medical technicians were allowed to perform electrocardiograms. Paramedics were sometimes allowed to interpret ECGs, sometimes with the aid of computer algorithms or via electronic transmission to a physician.

ELSEVIER GLOBAL MEDICAL NEWS

Delays in reperfusion were substantially reduced for patients with ST-segment elevation myocardial infarction after a statewide program was introduced in North Carolina.

The results of the program were announced on Nov. 4 at the annual scientific sessions of the American Heart Association in Orlando and simultaneously published online (JAMA 2007 Nov. 4 [Epubdoi:10.1001/jama.298.20.joc70124]).

Described as “one of the largest and most extensive regional systems … for the reperfusion of STEMI developed in the United States,” the program was modeled on systems for general trauma care. The program streamlined protocols and coordinated emergency medical services, hospital emergency departments, catheterization labs, and interhospital transfer, according to Dr. Christopher B. Granger of the division of cardiology at Duke University, Durham, N.C., and his associates.

After this program was instituted, the proportion of PCI patients who achieved door-to-device times of 90 minutes or less increased from 57% to 72%, and the median interval decreased from 85 minutes to 74 minutes, the researchers noted.

For patients who presented to hospitals that didn't perform PCI and therefore had to be transferred, the median door-to-device time dropped from 165 minutes to 128 minutes. Median door-in to door-out times decreased from 120 minutes to 71 minutes, “one of the greatest reductions observed in the study,” Dr. Granger and his associates said.

For patients undergoing fibrinolysis, the proportion who achieved door-to-needle times of less than 30 minutes rose from 35% to 52%, and the median interval decreased from 35 minutes to 29 minutes.

The program shaved times by eliminating waits for a cardiology consultation and by having an on-call interventional cardiologist identified at all times.

The emergency physician or paramedic could activate the nearest catheterization laboratory at any hour on any day of the week with a single phone call. Emergency department physicians or medical technicians were allowed to start treatment without waits for a cardiology consultation.

The on-call interventional cardiologist eliminated delays that result when “trying to determine which cardiologist from several competing groups would intervene.” Time to treatment was trimmed in remote areas by encouraging the use of local ambulances rather than helicopters or mobile critical care units. Other strategies included leaving patients “on the stretcher” when appropriate for more rapid evaluation and transfer.

Since STEMI “was a relatively infrequent event for most emergency personnel” to encounter, the program established a specific reperfusion plan that would cover most patients and would sidestep clinician delays that resulted from “indecision” and the need to develop individualized treatment plans.

ICU nurses staffed catheterization labs on an emergency basis, when night and weekend coverage by the usual staff couldn't be arranged. Certain procedures conducted by paramedics and medical technicians were modified to save time. For example, use of intravenous drips such as heparin or nitroglycerin were minimized because substantial delays were associated with establishing and changing infusion lines.

Additionally, the program addressed the limitations of regions with severe restrictions on available equipment and personnel. In resource-poor regions, intermediate-level emergency medical technicians were allowed to perform electrocardiograms. Paramedics were sometimes allowed to interpret ECGs, sometimes with the aid of computer algorithms or via electronic transmission to a physician.

ELSEVIER GLOBAL MEDICAL NEWS

Some types of disability are increasing in older obese Americans, even though recent improvements in cardiovascular health care have reduced the risk of disability in older normal-weight people, according to researchers at the University of Pennsylvania, Philadelphia.

Data from recent studies have suggested that the obese elderly population in the United States may have grown healthier since the 1960s, especially with the widespread use of lipid-lowering and antihypertensive drugs. “If the physiological manifestations of obesity are increasingly treatable, then some of the negative health effects of obesity may be in decline,” and obesity may be becoming less disabling, wrote researchers Dawn E. Alley, Ph.D., and Dr. Virginia W. Chang of the University of Pennsylvania, Philadelphia. On the other hand, they wrote, if improvements in health care are allowing obese people with chronic disease to live longer, then disability may be increasing in this population.

To examine whether the association between obesity and disability has changed over time, they assessed body mass index and disability in subjects aged 60 years and older, comparing data from the National Health and Nutrition Examination Surveys done in 1988–1994 (NHANES III) with data from the NHANES surveys of 1999–2004.

A total of 5,724 subjects from the earlier survey and 4,984 subjects from the later survey indicated whether they had no difficulty, some difficulty, much difficulty, or an inability to perform six tasks: walking one-quarter of a mile; walking up 10 steps without resting; stooping, crouching, or kneeling; lifting or carrying 10 pounds; walking between rooms on the same floor; and standing up from an armless chair. The subjects also reported on their ability to perform three activities of daily living: getting in and out of bed, eating, and dressing.

In the interval between the two NHANES studies, the prevalence of functional impairment did not change among normal-weight subjects, but it increased among obese subjects, from 37% to 42%. In a closer analysis that controlled for demographic characteristics, the odds of being functionally impaired rose 43% among the obese but showed no change among normal-weight subjects.

When the subjects were separated into categories of mild, moderate, and extreme obesity, they found that functional impairment had increased in all three. The overall increase in disability, therefore, was not solely because there are more people in the “extremely obese” category in later years, Dr. Alley and Dr. Chang said (JAMA 2007;298:2020–7).

Several obesity-related conditions were strongly associated with disability, including arthritis, diabetes, heart failure, MI, and stroke.

In an accompanying editorial, Dr. Edward W. Gregg of the Centers for Disease Control and Prevention, Atlanta, and Dr. Jack M. Guralnik of the National Institute on Aging, Bethesda, Md., said the most important finding in this study was that obese patients today are more likely to be disabled than obese patients were a decade earlier.

“This finding contrasts with the general reduction in disability reported for older adults” in the general population, they noted. “The authors speculate that this increased disability may be due to the average obese person of the current cohort having spent more years obese than in previous cohorts” and thus having more cumulative exposure to disability-inducing obesit (JAMA 2007;298:2066–7).

“It is also possible that because of declining mortality rates, the obese segment of the population is now composed of more people with multiple chronic conditions who in previous decades would have died at a younger age,” they wrote.

Some types of disability are increasing in older obese Americans, even though recent improvements in cardiovascular health care have reduced the risk of disability in older normal-weight people, according to researchers at the University of Pennsylvania, Philadelphia.

Data from recent studies have suggested that the obese elderly population in the United States may have grown healthier since the 1960s, especially with the widespread use of lipid-lowering and antihypertensive drugs. “If the physiological manifestations of obesity are increasingly treatable, then some of the negative health effects of obesity may be in decline,” and obesity may be becoming less disabling, wrote researchers Dawn E. Alley, Ph.D., and Dr. Virginia W. Chang of the University of Pennsylvania, Philadelphia. On the other hand, they wrote, if improvements in health care are allowing obese people with chronic disease to live longer, then disability may be increasing in this population.

To examine whether the association between obesity and disability has changed over time, they assessed body mass index and disability in subjects aged 60 years and older, comparing data from the National Health and Nutrition Examination Surveys done in 1988–1994 (NHANES III) with data from the NHANES surveys of 1999–2004.

A total of 5,724 subjects from the earlier survey and 4,984 subjects from the later survey indicated whether they had no difficulty, some difficulty, much difficulty, or an inability to perform six tasks: walking one-quarter of a mile; walking up 10 steps without resting; stooping, crouching, or kneeling; lifting or carrying 10 pounds; walking between rooms on the same floor; and standing up from an armless chair. The subjects also reported on their ability to perform three activities of daily living: getting in and out of bed, eating, and dressing.

In the interval between the two NHANES studies, the prevalence of functional impairment did not change among normal-weight subjects, but it increased among obese subjects, from 37% to 42%. In a closer analysis that controlled for demographic characteristics, the odds of being functionally impaired rose 43% among the obese but showed no change among normal-weight subjects.

When the subjects were separated into categories of mild, moderate, and extreme obesity, they found that functional impairment had increased in all three. The overall increase in disability, therefore, was not solely because there are more people in the “extremely obese” category in later years, Dr. Alley and Dr. Chang said (JAMA 2007;298:2020–7).

Several obesity-related conditions were strongly associated with disability, including arthritis, diabetes, heart failure, MI, and stroke.

In an accompanying editorial, Dr. Edward W. Gregg of the Centers for Disease Control and Prevention, Atlanta, and Dr. Jack M. Guralnik of the National Institute on Aging, Bethesda, Md., said the most important finding in this study was that obese patients today are more likely to be disabled than obese patients were a decade earlier.

“This finding contrasts with the general reduction in disability reported for older adults” in the general population, they noted. “The authors speculate that this increased disability may be due to the average obese person of the current cohort having spent more years obese than in previous cohorts” and thus having more cumulative exposure to disability-inducing obesit (JAMA 2007;298:2066–7).

“It is also possible that because of declining mortality rates, the obese segment of the population is now composed of more people with multiple chronic conditions who in previous decades would have died at a younger age,” they wrote.

Some types of disability are increasing in older obese Americans, even though recent improvements in cardiovascular health care have reduced the risk of disability in older normal-weight people, according to researchers at the University of Pennsylvania, Philadelphia.

Data from recent studies have suggested that the obese elderly population in the United States may have grown healthier since the 1960s, especially with the widespread use of lipid-lowering and antihypertensive drugs. “If the physiological manifestations of obesity are increasingly treatable, then some of the negative health effects of obesity may be in decline,” and obesity may be becoming less disabling, wrote researchers Dawn E. Alley, Ph.D., and Dr. Virginia W. Chang of the University of Pennsylvania, Philadelphia. On the other hand, they wrote, if improvements in health care are allowing obese people with chronic disease to live longer, then disability may be increasing in this population.

To examine whether the association between obesity and disability has changed over time, they assessed body mass index and disability in subjects aged 60 years and older, comparing data from the National Health and Nutrition Examination Surveys done in 1988–1994 (NHANES III) with data from the NHANES surveys of 1999–2004.

A total of 5,724 subjects from the earlier survey and 4,984 subjects from the later survey indicated whether they had no difficulty, some difficulty, much difficulty, or an inability to perform six tasks: walking one-quarter of a mile; walking up 10 steps without resting; stooping, crouching, or kneeling; lifting or carrying 10 pounds; walking between rooms on the same floor; and standing up from an armless chair. The subjects also reported on their ability to perform three activities of daily living: getting in and out of bed, eating, and dressing.

In the interval between the two NHANES studies, the prevalence of functional impairment did not change among normal-weight subjects, but it increased among obese subjects, from 37% to 42%. In a closer analysis that controlled for demographic characteristics, the odds of being functionally impaired rose 43% among the obese but showed no change among normal-weight subjects.

When the subjects were separated into categories of mild, moderate, and extreme obesity, they found that functional impairment had increased in all three. The overall increase in disability, therefore, was not solely because there are more people in the “extremely obese” category in later years, Dr. Alley and Dr. Chang said (JAMA 2007;298:2020–7).

Several obesity-related conditions were strongly associated with disability, including arthritis, diabetes, heart failure, MI, and stroke.

In an accompanying editorial, Dr. Edward W. Gregg of the Centers for Disease Control and Prevention, Atlanta, and Dr. Jack M. Guralnik of the National Institute on Aging, Bethesda, Md., said the most important finding in this study was that obese patients today are more likely to be disabled than obese patients were a decade earlier.

“This finding contrasts with the general reduction in disability reported for older adults” in the general population, they noted. “The authors speculate that this increased disability may be due to the average obese person of the current cohort having spent more years obese than in previous cohorts” and thus having more cumulative exposure to disability-inducing obesit (JAMA 2007;298:2066–7).

“It is also possible that because of declining mortality rates, the obese segment of the population is now composed of more people with multiple chronic conditions who in previous decades would have died at a younger age,” they wrote.

The antioxidant β-carotene does not improve cognitive performance among healthy older men in the short term, according to a subgroup analysis of data from a longitudinal study.

These findings add to the growing list of study results concluding that counteracting long-term oxidative stress with antioxidants doesn't appear to protect against cognitive decline. However, it is still possible that long-term treatment with β-carotene may confer “modest” neuroprotection, reported Francine Grodstein, Sc.D., and her associates in the Physicians' Health Study (PHS) II.

The PHS II is an ancillary study of the Physicians' Health Study, a randomized clinical trial assessing whether vitamin supplements prevent cancer and cardiovascular disease. Cognitive evaluations were added to the trial to assess any cognitive impact of supplementation. The PHS II study extended the follow-up on a subgroup of 7,641 male physicians (average age 73 years) from 1997 through 2003, and also added 7,000 new recruits aged 55 and older in 1998–2001.

Dr. Grodstein and her coinvestigators assessed cognitive outcomes for 2,989 subjects who took placebo and 2,967 subjects who took β-carotene for various durations that ranged from 2 months to 20 years. Verbal memory, immediate and delayed recall, category fluency, and mental state were assessed.

β-Carotene yielded no cognitive benefits in subjects who had taken it for 3 years or less, according to Dr. Grodstein of Harvard School of Public Health, Boston, and her associates.

However, subjects who had taken β-carotene for at least 15 years showed better scores on several cognitive measures than did those who had taken placebo. “In general, the effect of long-term beta carotene treatment was comparable to delaying cognitive aging by 1 to 1.5 years,” the researchers said (Arch. Intern. Med. 2007;167:2184–90).

Nevertheless, in a subset of 4,074 subjects who had further cognitive assessments 2–4 years later, these differences were found to be not statistically significant.

Regarding this last finding, Dr. Kristine Yaffe of the University of California, San Francisco, said in an editorial accompanying this report, “it is curious that the authors minimize the results for approximately 4,000 men who had repeated cognitive testing.”

Dr. Yaffe noted that “several trials have examined relatively long durations of antioxidant exposure (up to 10 years) and failed to find an effect of treatment on cognitive outcomes” (Arch. Intern. Med. 2007;167:2167–8).

“For the clinician, there is no convincing justification to recommend the use of antioxidant dietary supplements to maintain cognitive performance in cognitively normal adults or in those with mild cognitive impairment. Furthermore, there is new concern that high-dose antioxidant supplementation, including beta carotene, may have adverse health consequences including mortality,” Dr. Yaffe said.

β-Carotene had no benefit for those taking it less than 3 years. ©photo-Dave/Fotolia.com

The antioxidant β-carotene does not improve cognitive performance among healthy older men in the short term, according to a subgroup analysis of data from a longitudinal study.

These findings add to the growing list of study results concluding that counteracting long-term oxidative stress with antioxidants doesn't appear to protect against cognitive decline. However, it is still possible that long-term treatment with β-carotene may confer “modest” neuroprotection, reported Francine Grodstein, Sc.D., and her associates in the Physicians' Health Study (PHS) II.

The PHS II is an ancillary study of the Physicians' Health Study, a randomized clinical trial assessing whether vitamin supplements prevent cancer and cardiovascular disease. Cognitive evaluations were added to the trial to assess any cognitive impact of supplementation. The PHS II study extended the follow-up on a subgroup of 7,641 male physicians (average age 73 years) from 1997 through 2003, and also added 7,000 new recruits aged 55 and older in 1998–2001.

Dr. Grodstein and her coinvestigators assessed cognitive outcomes for 2,989 subjects who took placebo and 2,967 subjects who took β-carotene for various durations that ranged from 2 months to 20 years. Verbal memory, immediate and delayed recall, category fluency, and mental state were assessed.

β-Carotene yielded no cognitive benefits in subjects who had taken it for 3 years or less, according to Dr. Grodstein of Harvard School of Public Health, Boston, and her associates.

However, subjects who had taken β-carotene for at least 15 years showed better scores on several cognitive measures than did those who had taken placebo. “In general, the effect of long-term beta carotene treatment was comparable to delaying cognitive aging by 1 to 1.5 years,” the researchers said (Arch. Intern. Med. 2007;167:2184–90).

Nevertheless, in a subset of 4,074 subjects who had further cognitive assessments 2–4 years later, these differences were found to be not statistically significant.

Regarding this last finding, Dr. Kristine Yaffe of the University of California, San Francisco, said in an editorial accompanying this report, “it is curious that the authors minimize the results for approximately 4,000 men who had repeated cognitive testing.”

Dr. Yaffe noted that “several trials have examined relatively long durations of antioxidant exposure (up to 10 years) and failed to find an effect of treatment on cognitive outcomes” (Arch. Intern. Med. 2007;167:2167–8).

“For the clinician, there is no convincing justification to recommend the use of antioxidant dietary supplements to maintain cognitive performance in cognitively normal adults or in those with mild cognitive impairment. Furthermore, there is new concern that high-dose antioxidant supplementation, including beta carotene, may have adverse health consequences including mortality,” Dr. Yaffe said.

β-Carotene had no benefit for those taking it less than 3 years. ©photo-Dave/Fotolia.com

The antioxidant β-carotene does not improve cognitive performance among healthy older men in the short term, according to a subgroup analysis of data from a longitudinal study.

These findings add to the growing list of study results concluding that counteracting long-term oxidative stress with antioxidants doesn't appear to protect against cognitive decline. However, it is still possible that long-term treatment with β-carotene may confer “modest” neuroprotection, reported Francine Grodstein, Sc.D., and her associates in the Physicians' Health Study (PHS) II.

The PHS II is an ancillary study of the Physicians' Health Study, a randomized clinical trial assessing whether vitamin supplements prevent cancer and cardiovascular disease. Cognitive evaluations were added to the trial to assess any cognitive impact of supplementation. The PHS II study extended the follow-up on a subgroup of 7,641 male physicians (average age 73 years) from 1997 through 2003, and also added 7,000 new recruits aged 55 and older in 1998–2001.

Dr. Grodstein and her coinvestigators assessed cognitive outcomes for 2,989 subjects who took placebo and 2,967 subjects who took β-carotene for various durations that ranged from 2 months to 20 years. Verbal memory, immediate and delayed recall, category fluency, and mental state were assessed.

β-Carotene yielded no cognitive benefits in subjects who had taken it for 3 years or less, according to Dr. Grodstein of Harvard School of Public Health, Boston, and her associates.

However, subjects who had taken β-carotene for at least 15 years showed better scores on several cognitive measures than did those who had taken placebo. “In general, the effect of long-term beta carotene treatment was comparable to delaying cognitive aging by 1 to 1.5 years,” the researchers said (Arch. Intern. Med. 2007;167:2184–90).

Nevertheless, in a subset of 4,074 subjects who had further cognitive assessments 2–4 years later, these differences were found to be not statistically significant.

Regarding this last finding, Dr. Kristine Yaffe of the University of California, San Francisco, said in an editorial accompanying this report, “it is curious that the authors minimize the results for approximately 4,000 men who had repeated cognitive testing.”

Dr. Yaffe noted that “several trials have examined relatively long durations of antioxidant exposure (up to 10 years) and failed to find an effect of treatment on cognitive outcomes” (Arch. Intern. Med. 2007;167:2167–8).

“For the clinician, there is no convincing justification to recommend the use of antioxidant dietary supplements to maintain cognitive performance in cognitively normal adults or in those with mild cognitive impairment. Furthermore, there is new concern that high-dose antioxidant supplementation, including beta carotene, may have adverse health consequences including mortality,” Dr. Yaffe said.

β-Carotene had no benefit for those taking it less than 3 years. ©photo-Dave/Fotolia.com

In women who test positive for human papillomavirus DNA, the bivalent HPV-16/18 vaccination does not induce or accelerate clearance of the infection, according to a phase III study.

Human papillomavirus (HPV) vaccination induces cell-mediated immune responses that are traditionally involved in the eradication of infection, and it has been suggested that the vaccine might benefit women who are already infected, perhaps by enhancing viral clearance. Researchers examined the issue using a cohort drawn from a large, ongoing randomized clinical trial of vaccine efficacy.

The subjects in the main study of vaccine efficacy were nearly 7,500 women aged 18-25 years who resided in Costa Rica, where cervical cancer screening programs incorporate HPV DNA testing along with Pap tests. "Because current management protocols often involve retesting HPV-positive women within months of an initial HPV-positive result before treatment decisions are made, understanding the impact of vaccination on viral clearance in the first 6-12 months following an initial HPV-positive result would be informative," wrote study investigators Dr. Allan Hildesheim of the National Cancer Institute, Rockville, Md., and his associates.

The investigators assessed viral clearance in a subset of 2,055 subjects who were positive for HPV DNA and received either a control immunization or the bivalent HPV-16/18 vaccine that contains viruslike particles only from HPV-16 and HPV-18. This formulation has been approved for use in Australia and is under review for use in the United States and other countries, they noted.

Clearance rates for HPV-16 and/or HPV-18 were not significantly different between the active treatment and placebo treatment groups either 6 months after the initial vaccination was given (33.4% vs. 31.6%) or at 12 months, when the entire series of vaccinations was completed (48.8% vs. 49.8%). In addition, there was no evidence of a vaccine effect in any of several subgroups studied.

The trial was funded by the National Cancer Institute and the National Institutes of Health. Although Dr. Hildesheim reported having no conflicts of interest, other study investigators reported receiving financial support through royalties and employment from GlaxoSmithKline—manufacturer of the vaccine used in the study—and Merck.

In women who test positive for human papillomavirus DNA, the bivalent HPV-16/18 vaccination does not induce or accelerate clearance of the infection, according to a phase III study.

Human papillomavirus (HPV) vaccination induces cell-mediated immune responses that are traditionally involved in the eradication of infection, and it has been suggested that the vaccine might benefit women who are already infected, perhaps by enhancing viral clearance. Researchers examined the issue using a cohort drawn from a large, ongoing randomized clinical trial of vaccine efficacy.

The subjects in the main study of vaccine efficacy were nearly 7,500 women aged 18-25 years who resided in Costa Rica, where cervical cancer screening programs incorporate HPV DNA testing along with Pap tests. "Because current management protocols often involve retesting HPV-positive women within months of an initial HPV-positive result before treatment decisions are made, understanding the impact of vaccination on viral clearance in the first 6-12 months following an initial HPV-positive result would be informative," wrote study investigators Dr. Allan Hildesheim of the National Cancer Institute, Rockville, Md., and his associates.

The investigators assessed viral clearance in a subset of 2,055 subjects who were positive for HPV DNA and received either a control immunization or the bivalent HPV-16/18 vaccine that contains viruslike particles only from HPV-16 and HPV-18. This formulation has been approved for use in Australia and is under review for use in the United States and other countries, they noted.

Clearance rates for HPV-16 and/or HPV-18 were not significantly different between the active treatment and placebo treatment groups either 6 months after the initial vaccination was given (33.4% vs. 31.6%) or at 12 months, when the entire series of vaccinations was completed (48.8% vs. 49.8%). In addition, there was no evidence of a vaccine effect in any of several subgroups studied.

The trial was funded by the National Cancer Institute and the National Institutes of Health. Although Dr. Hildesheim reported having no conflicts of interest, other study investigators reported receiving financial support through royalties and employment from GlaxoSmithKline—manufacturer of the vaccine used in the study—and Merck.

In women who test positive for human papillomavirus DNA, the bivalent HPV-16/18 vaccination does not induce or accelerate clearance of the infection, according to a phase III study.

Human papillomavirus (HPV) vaccination induces cell-mediated immune responses that are traditionally involved in the eradication of infection, and it has been suggested that the vaccine might benefit women who are already infected, perhaps by enhancing viral clearance. Researchers examined the issue using a cohort drawn from a large, ongoing randomized clinical trial of vaccine efficacy.

The subjects in the main study of vaccine efficacy were nearly 7,500 women aged 18-25 years who resided in Costa Rica, where cervical cancer screening programs incorporate HPV DNA testing along with Pap tests. "Because current management protocols often involve retesting HPV-positive women within months of an initial HPV-positive result before treatment decisions are made, understanding the impact of vaccination on viral clearance in the first 6-12 months following an initial HPV-positive result would be informative," wrote study investigators Dr. Allan Hildesheim of the National Cancer Institute, Rockville, Md., and his associates.

The investigators assessed viral clearance in a subset of 2,055 subjects who were positive for HPV DNA and received either a control immunization or the bivalent HPV-16/18 vaccine that contains viruslike particles only from HPV-16 and HPV-18. This formulation has been approved for use in Australia and is under review for use in the United States and other countries, they noted.

Clearance rates for HPV-16 and/or HPV-18 were not significantly different between the active treatment and placebo treatment groups either 6 months after the initial vaccination was given (33.4% vs. 31.6%) or at 12 months, when the entire series of vaccinations was completed (48.8% vs. 49.8%). In addition, there was no evidence of a vaccine effect in any of several subgroups studied.

The trial was funded by the National Cancer Institute and the National Institutes of Health. Although Dr. Hildesheim reported having no conflicts of interest, other study investigators reported receiving financial support through royalties and employment from GlaxoSmithKline—manufacturer of the vaccine used in the study—and Merck.

Repeated courses of prenatal corticosteroids in pregnant women at high risk of preterm delivery do not appear to have adverse effects on neurocognitive or physical development of the child at 2 years of age, compared with a single course, investigators in two large randomized clinical trials reported.

Both research groups termed these findings “reassuring,” given that repeated doses have already become commonplace in the United States, the United Kingdom, and Australia.

U.S. clinicians have widely adopted weekly intramuscular injections of corticosteroids in high-risk pregnancies, even though there is insufficient data to support this practice. Moreover, animal and observational human studies have suggested that repeated steroid injections may inhibit the offspring's growth, impair brain development, predispose to neurosensory disability, increase aggression and hyperactivity, and raise blood pressure, investigators noted.

Current guidelines recommend repeated corticosteroid courses only in subjects participating in large randomized, controlled clinical trials to assess both short-term and long-term safety and efficacy of the treatment. Two such clinical trials are the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) and a National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network trial.

Investigators in both studies previously reported their findings in neonates who were exposed to either a single dose or weekly repeated doses of steroids. Both studies showed better neonatal outcomes after repeated doses, with less need for mechanical respiratory support and surfactant use, less respiratory distress syndrome, and less serious neonatal morbidity.

Both studies also raised concerns about lower birth weight and smaller head circumference after repeated doses, however, and suggested that short-term benefits in lung maturation might be offset by possible long-term deficits in neurologic development and physical growth. Both research groups now report normal physical and neurocognitive outcomes in the same subjects at age 2-3 years.

In the ACTORDS study, Dr. Caroline A. Crowther of the University of Adelaide (South Australia) and her associates assessed 1,047 children who had been delivered at 23 medical centers.

Women who received an initial course of steroids at least 7 days earlier were randomly assigned to receive an injection of 11.4 mg betamethasone or saline placebo. The dose was repeated weekly if the mother remained at risk of preterm delivery and gestation was less than 32 weeks.

The rates of survival free of major disability were similar in children whose mothers had received repeated steroid injections and those whose mothers had received placebo injections (84% vs. 81%).

There also were no significant differences between the two groups in weight, height, or head circumference; blood pressure; the use of health care resources; mortality; neurosensory impairments such as cerebral palsy, blindness, or developmental delay; or behavioral factors such as emotional reactivity, anxiety, depression, aggression, or sleep problems.

There were more attention problems and more aggression among children exposed to repeated injections, but those associations may have been due to chance, Dr. Crowther and associates said.

Further follow-up is crucial, because other important cognitive outcomes, such as executive function, cannot be determined until the children reach school age.

Still, the investigators noted that “clinicians may wish to consider the use of a single injection of Celestone Chronodose, or equivalent, repeated weekly, if the woman remains at risk for very preterm delivery” 7 days after receiving an initial course (N. Engl. J. Med. 2007;357:1179-89).

In the MFMU study, Dr. Ronald J. Wapner of Columbia University, New York, and his associates assessed 248 children aged approximately 30 months who had been exposed to repeated corticosteroid courses in utero (12 mg given intramuscularly and repeated at 24 hours) and 238 who had been exposed to a single steroid course initially and repeated placebo courses later.

As in the ACTORDS trial, the MFMU researchers found no significant differences between the two groups in anthropomorphic measures; scores on mental and psychomotor tests; blood pressure; or other health outcomes such as seizures, pneumonia, and the need for hospitalization during infancy.

They did find an increased frequency of cerebral palsy in children who had been exposed to repeated courses of corticosteroids, compared with a single course (2.9% vs. 0.5%). Although this difference was not statistically significant, it is still cause for concern, Dr. Wapner and his associates said (N. Engl. J. Med. 2007;357:1190-8).

Like the ACTORDS investigators, the MFMU researchers emphasized that further follow-up of these subjects through later childhood is critical.

And although they characterized these findings as “reassuring,” Dr. Wapner and his associates concluded that their results argue against giving repeated prenatal corticosteroids until more data are collected.

This approach may improve the condition of the neonate, but it does not convey long-term benefit and may cause possible harm in later life, they said.

Repeated courses of prenatal corticosteroids in pregnant women at high risk of preterm delivery do not appear to have adverse effects on neurocognitive or physical development of the child at 2 years of age, compared with a single course, investigators in two large randomized clinical trials reported.

Both research groups termed these findings “reassuring,” given that repeated doses have already become commonplace in the United States, the United Kingdom, and Australia.

U.S. clinicians have widely adopted weekly intramuscular injections of corticosteroids in high-risk pregnancies, even though there is insufficient data to support this practice. Moreover, animal and observational human studies have suggested that repeated steroid injections may inhibit the offspring's growth, impair brain development, predispose to neurosensory disability, increase aggression and hyperactivity, and raise blood pressure, investigators noted.

Current guidelines recommend repeated corticosteroid courses only in subjects participating in large randomized, controlled clinical trials to assess both short-term and long-term safety and efficacy of the treatment. Two such clinical trials are the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) and a National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network trial.

Investigators in both studies previously reported their findings in neonates who were exposed to either a single dose or weekly repeated doses of steroids. Both studies showed better neonatal outcomes after repeated doses, with less need for mechanical respiratory support and surfactant use, less respiratory distress syndrome, and less serious neonatal morbidity.

Both studies also raised concerns about lower birth weight and smaller head circumference after repeated doses, however, and suggested that short-term benefits in lung maturation might be offset by possible long-term deficits in neurologic development and physical growth. Both research groups now report normal physical and neurocognitive outcomes in the same subjects at age 2-3 years.

In the ACTORDS study, Dr. Caroline A. Crowther of the University of Adelaide (South Australia) and her associates assessed 1,047 children who had been delivered at 23 medical centers.

Women who received an initial course of steroids at least 7 days earlier were randomly assigned to receive an injection of 11.4 mg betamethasone or saline placebo. The dose was repeated weekly if the mother remained at risk of preterm delivery and gestation was less than 32 weeks.

The rates of survival free of major disability were similar in children whose mothers had received repeated steroid injections and those whose mothers had received placebo injections (84% vs. 81%).

There also were no significant differences between the two groups in weight, height, or head circumference; blood pressure; the use of health care resources; mortality; neurosensory impairments such as cerebral palsy, blindness, or developmental delay; or behavioral factors such as emotional reactivity, anxiety, depression, aggression, or sleep problems.

There were more attention problems and more aggression among children exposed to repeated injections, but those associations may have been due to chance, Dr. Crowther and associates said.

Further follow-up is crucial, because other important cognitive outcomes, such as executive function, cannot be determined until the children reach school age.

Still, the investigators noted that “clinicians may wish to consider the use of a single injection of Celestone Chronodose, or equivalent, repeated weekly, if the woman remains at risk for very preterm delivery” 7 days after receiving an initial course (N. Engl. J. Med. 2007;357:1179-89).

In the MFMU study, Dr. Ronald J. Wapner of Columbia University, New York, and his associates assessed 248 children aged approximately 30 months who had been exposed to repeated corticosteroid courses in utero (12 mg given intramuscularly and repeated at 24 hours) and 238 who had been exposed to a single steroid course initially and repeated placebo courses later.

As in the ACTORDS trial, the MFMU researchers found no significant differences between the two groups in anthropomorphic measures; scores on mental and psychomotor tests; blood pressure; or other health outcomes such as seizures, pneumonia, and the need for hospitalization during infancy.

They did find an increased frequency of cerebral palsy in children who had been exposed to repeated courses of corticosteroids, compared with a single course (2.9% vs. 0.5%). Although this difference was not statistically significant, it is still cause for concern, Dr. Wapner and his associates said (N. Engl. J. Med. 2007;357:1190-8).

Like the ACTORDS investigators, the MFMU researchers emphasized that further follow-up of these subjects through later childhood is critical.

And although they characterized these findings as “reassuring,” Dr. Wapner and his associates concluded that their results argue against giving repeated prenatal corticosteroids until more data are collected.

This approach may improve the condition of the neonate, but it does not convey long-term benefit and may cause possible harm in later life, they said.

Repeated courses of prenatal corticosteroids in pregnant women at high risk of preterm delivery do not appear to have adverse effects on neurocognitive or physical development of the child at 2 years of age, compared with a single course, investigators in two large randomized clinical trials reported.

Both research groups termed these findings “reassuring,” given that repeated doses have already become commonplace in the United States, the United Kingdom, and Australia.

U.S. clinicians have widely adopted weekly intramuscular injections of corticosteroids in high-risk pregnancies, even though there is insufficient data to support this practice. Moreover, animal and observational human studies have suggested that repeated steroid injections may inhibit the offspring's growth, impair brain development, predispose to neurosensory disability, increase aggression and hyperactivity, and raise blood pressure, investigators noted.

Current guidelines recommend repeated corticosteroid courses only in subjects participating in large randomized, controlled clinical trials to assess both short-term and long-term safety and efficacy of the treatment. Two such clinical trials are the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) and a National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network trial.

Investigators in both studies previously reported their findings in neonates who were exposed to either a single dose or weekly repeated doses of steroids. Both studies showed better neonatal outcomes after repeated doses, with less need for mechanical respiratory support and surfactant use, less respiratory distress syndrome, and less serious neonatal morbidity.

Both studies also raised concerns about lower birth weight and smaller head circumference after repeated doses, however, and suggested that short-term benefits in lung maturation might be offset by possible long-term deficits in neurologic development and physical growth. Both research groups now report normal physical and neurocognitive outcomes in the same subjects at age 2-3 years.

In the ACTORDS study, Dr. Caroline A. Crowther of the University of Adelaide (South Australia) and her associates assessed 1,047 children who had been delivered at 23 medical centers.

Women who received an initial course of steroids at least 7 days earlier were randomly assigned to receive an injection of 11.4 mg betamethasone or saline placebo. The dose was repeated weekly if the mother remained at risk of preterm delivery and gestation was less than 32 weeks.

The rates of survival free of major disability were similar in children whose mothers had received repeated steroid injections and those whose mothers had received placebo injections (84% vs. 81%).

There also were no significant differences between the two groups in weight, height, or head circumference; blood pressure; the use of health care resources; mortality; neurosensory impairments such as cerebral palsy, blindness, or developmental delay; or behavioral factors such as emotional reactivity, anxiety, depression, aggression, or sleep problems.

There were more attention problems and more aggression among children exposed to repeated injections, but those associations may have been due to chance, Dr. Crowther and associates said.

Further follow-up is crucial, because other important cognitive outcomes, such as executive function, cannot be determined until the children reach school age.

Still, the investigators noted that “clinicians may wish to consider the use of a single injection of Celestone Chronodose, or equivalent, repeated weekly, if the woman remains at risk for very preterm delivery” 7 days after receiving an initial course (N. Engl. J. Med. 2007;357:1179-89).

In the MFMU study, Dr. Ronald J. Wapner of Columbia University, New York, and his associates assessed 248 children aged approximately 30 months who had been exposed to repeated corticosteroid courses in utero (12 mg given intramuscularly and repeated at 24 hours) and 238 who had been exposed to a single steroid course initially and repeated placebo courses later.

As in the ACTORDS trial, the MFMU researchers found no significant differences between the two groups in anthropomorphic measures; scores on mental and psychomotor tests; blood pressure; or other health outcomes such as seizures, pneumonia, and the need for hospitalization during infancy.

They did find an increased frequency of cerebral palsy in children who had been exposed to repeated courses of corticosteroids, compared with a single course (2.9% vs. 0.5%). Although this difference was not statistically significant, it is still cause for concern, Dr. Wapner and his associates said (N. Engl. J. Med. 2007;357:1190-8).

Like the ACTORDS investigators, the MFMU researchers emphasized that further follow-up of these subjects through later childhood is critical.

And although they characterized these findings as “reassuring,” Dr. Wapner and his associates concluded that their results argue against giving repeated prenatal corticosteroids until more data are collected.

This approach may improve the condition of the neonate, but it does not convey long-term benefit and may cause possible harm in later life, they said.

Testing for human papillomavirus DNA, either alone or in addition to routine Pap screening, improves the detection of cervical intraepithelial neoplasia, two research groups reported in separate studies.

One of the groups of investigators also found that adding human papillomavirus (HPV) DNA testing to Pap testing also decreased the incidence of high-grade lesions and cancers found on subsequent screens over the next few years.

“This result indicates that the improved sensitivity of HPV testing is not merely due to overdiagnosis but is attributable, at least in part, to earlier diagnosis of lesions that do not regress,” they said.

In an editorial comment accompanying the two reports, Dr. Carolyn D. Runowicz of the University of Connecticut Health Center, Farmington, said that if additional studies confirm these findings, HPV DNA testing may eventually replace cytologic testing.

However, “we are not there yet,” she cautioned.

In the first study, Dr. Marie-Hélène Mayrand and her associates in the Canadian Cervical Cancer Screening Trial (CCCaST) directly compared HPV and Pap testing as stand-alone screens for cervical cancers and their high-grade precursors in more than 10,000 women aged 30–69 years who presented to 30 Canadian clinics for routine screening in 2002–2005. A total of 5,059 women were randomly assigned to undergo Pap testing followed by HPV testing, and the remaining 5,095 to undergo HPV testing followed by Pap testing.

Both tests were found to have negative predictive values higher than 99%.

However, HPV testing proved to be 39% more sensitive than Pap testing. This improved sensitivity was not achieved at the expense of drastically reduced specificity, as HPV testing was only 2.7% less specific than Pap testing, said Dr. Mayrand of McGill University, Montreal, and her associates.

Moreover, combining the results of both tests improved sensitivity only “marginally” over that achieved with HPV testing alone, “while doubling the number of tests and increasing referrals” for colposcopy.

“It is difficult to predict whether a change from Pap testing to HPV testing will further reduce the rates of death from cervical cancer.” However, “we believe that a shift from cellular to viral tests, coupled with education and vaccination, will contribute to a more efficient control of cervical cancer,” the investigators said (N. Engl. J. Med. 2007;357:1579–88).

The second study was a population-based trial in which more than 12,000 women in their mid-30s in five Swedish cities were randomly assigned to undergo Pap testing plus HPV DNA testing or Pap testing alone between 1997 and 2000. With the addition of HPV testing, 51% more cases of grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cancer were detected, said Dr. Pontus Naucler of Lund (Sweden) University and associates.

The incidence of such lesions detected on subsequent screens during 4 years of follow-up decreased by a statistically significant 47%. This “represents a gain in lead time”—earlier diagnosis of high-grade lesions rather than overdiagnosis of lesions that otherwise would have regressed spontaneously, they noted (N. Engl. J. Med. 2007;357:1589–97).

This also means that HPV testing may reduce mortality from cervical cancer in women who undergo screening less often than is recommended, Dr. Naucler and associates added.

Dr. Runowicz said that if further studies confirm these findings, “there will be a need to develop a rapid, simple, accurate, and affordable HPV DNA test.” New algorithms for screening also will need to be developed.

The optimal screening approach—based on cytology, virology, or both—“will depend on the prevalence of disease, access to screening, and available resources” in any given region, Dr. Runowicz noted (N. Engl. J. Med. 2007;357:1650–3).

The CCCaST study was supported by a grant from the Canadian Institutes of Health Research and partially by an unrestricted grant from Merck Frosst Canada Ltd. The Swedish study was supported by grants from the Swedish Cancer Society and Europe Against Cancer.

Testing for human papillomavirus DNA, either alone or in addition to routine Pap screening, improves the detection of cervical intraepithelial neoplasia, two research groups reported in separate studies.

One of the groups of investigators also found that adding human papillomavirus (HPV) DNA testing to Pap testing also decreased the incidence of high-grade lesions and cancers found on subsequent screens over the next few years.

“This result indicates that the improved sensitivity of HPV testing is not merely due to overdiagnosis but is attributable, at least in part, to earlier diagnosis of lesions that do not regress,” they said.

In an editorial comment accompanying the two reports, Dr. Carolyn D. Runowicz of the University of Connecticut Health Center, Farmington, said that if additional studies confirm these findings, HPV DNA testing may eventually replace cytologic testing.

However, “we are not there yet,” she cautioned.

In the first study, Dr. Marie-Hélène Mayrand and her associates in the Canadian Cervical Cancer Screening Trial (CCCaST) directly compared HPV and Pap testing as stand-alone screens for cervical cancers and their high-grade precursors in more than 10,000 women aged 30–69 years who presented to 30 Canadian clinics for routine screening in 2002–2005. A total of 5,059 women were randomly assigned to undergo Pap testing followed by HPV testing, and the remaining 5,095 to undergo HPV testing followed by Pap testing.

Both tests were found to have negative predictive values higher than 99%.

However, HPV testing proved to be 39% more sensitive than Pap testing. This improved sensitivity was not achieved at the expense of drastically reduced specificity, as HPV testing was only 2.7% less specific than Pap testing, said Dr. Mayrand of McGill University, Montreal, and her associates.

Moreover, combining the results of both tests improved sensitivity only “marginally” over that achieved with HPV testing alone, “while doubling the number of tests and increasing referrals” for colposcopy.

“It is difficult to predict whether a change from Pap testing to HPV testing will further reduce the rates of death from cervical cancer.” However, “we believe that a shift from cellular to viral tests, coupled with education and vaccination, will contribute to a more efficient control of cervical cancer,” the investigators said (N. Engl. J. Med. 2007;357:1579–88).

The second study was a population-based trial in which more than 12,000 women in their mid-30s in five Swedish cities were randomly assigned to undergo Pap testing plus HPV DNA testing or Pap testing alone between 1997 and 2000. With the addition of HPV testing, 51% more cases of grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cancer were detected, said Dr. Pontus Naucler of Lund (Sweden) University and associates.

The incidence of such lesions detected on subsequent screens during 4 years of follow-up decreased by a statistically significant 47%. This “represents a gain in lead time”—earlier diagnosis of high-grade lesions rather than overdiagnosis of lesions that otherwise would have regressed spontaneously, they noted (N. Engl. J. Med. 2007;357:1589–97).

This also means that HPV testing may reduce mortality from cervical cancer in women who undergo screening less often than is recommended, Dr. Naucler and associates added.

Dr. Runowicz said that if further studies confirm these findings, “there will be a need to develop a rapid, simple, accurate, and affordable HPV DNA test.” New algorithms for screening also will need to be developed.

The optimal screening approach—based on cytology, virology, or both—“will depend on the prevalence of disease, access to screening, and available resources” in any given region, Dr. Runowicz noted (N. Engl. J. Med. 2007;357:1650–3).

The CCCaST study was supported by a grant from the Canadian Institutes of Health Research and partially by an unrestricted grant from Merck Frosst Canada Ltd. The Swedish study was supported by grants from the Swedish Cancer Society and Europe Against Cancer.

Testing for human papillomavirus DNA, either alone or in addition to routine Pap screening, improves the detection of cervical intraepithelial neoplasia, two research groups reported in separate studies.

One of the groups of investigators also found that adding human papillomavirus (HPV) DNA testing to Pap testing also decreased the incidence of high-grade lesions and cancers found on subsequent screens over the next few years.

“This result indicates that the improved sensitivity of HPV testing is not merely due to overdiagnosis but is attributable, at least in part, to earlier diagnosis of lesions that do not regress,” they said.

In an editorial comment accompanying the two reports, Dr. Carolyn D. Runowicz of the University of Connecticut Health Center, Farmington, said that if additional studies confirm these findings, HPV DNA testing may eventually replace cytologic testing.

However, “we are not there yet,” she cautioned.

In the first study, Dr. Marie-Hélène Mayrand and her associates in the Canadian Cervical Cancer Screening Trial (CCCaST) directly compared HPV and Pap testing as stand-alone screens for cervical cancers and their high-grade precursors in more than 10,000 women aged 30–69 years who presented to 30 Canadian clinics for routine screening in 2002–2005. A total of 5,059 women were randomly assigned to undergo Pap testing followed by HPV testing, and the remaining 5,095 to undergo HPV testing followed by Pap testing.

Both tests were found to have negative predictive values higher than 99%.

However, HPV testing proved to be 39% more sensitive than Pap testing. This improved sensitivity was not achieved at the expense of drastically reduced specificity, as HPV testing was only 2.7% less specific than Pap testing, said Dr. Mayrand of McGill University, Montreal, and her associates.

Moreover, combining the results of both tests improved sensitivity only “marginally” over that achieved with HPV testing alone, “while doubling the number of tests and increasing referrals” for colposcopy.

“It is difficult to predict whether a change from Pap testing to HPV testing will further reduce the rates of death from cervical cancer.” However, “we believe that a shift from cellular to viral tests, coupled with education and vaccination, will contribute to a more efficient control of cervical cancer,” the investigators said (N. Engl. J. Med. 2007;357:1579–88).

The second study was a population-based trial in which more than 12,000 women in their mid-30s in five Swedish cities were randomly assigned to undergo Pap testing plus HPV DNA testing or Pap testing alone between 1997 and 2000. With the addition of HPV testing, 51% more cases of grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cancer were detected, said Dr. Pontus Naucler of Lund (Sweden) University and associates.

The incidence of such lesions detected on subsequent screens during 4 years of follow-up decreased by a statistically significant 47%. This “represents a gain in lead time”—earlier diagnosis of high-grade lesions rather than overdiagnosis of lesions that otherwise would have regressed spontaneously, they noted (N. Engl. J. Med. 2007;357:1589–97).

This also means that HPV testing may reduce mortality from cervical cancer in women who undergo screening less often than is recommended, Dr. Naucler and associates added.

Dr. Runowicz said that if further studies confirm these findings, “there will be a need to develop a rapid, simple, accurate, and affordable HPV DNA test.” New algorithms for screening also will need to be developed.

The optimal screening approach—based on cytology, virology, or both—“will depend on the prevalence of disease, access to screening, and available resources” in any given region, Dr. Runowicz noted (N. Engl. J. Med. 2007;357:1650–3).

The CCCaST study was supported by a grant from the Canadian Institutes of Health Research and partially by an unrestricted grant from Merck Frosst Canada Ltd. The Swedish study was supported by grants from the Swedish Cancer Society and Europe Against Cancer.

A variation in the promoter region of the gene that encodes connective-tissue growth factor (CTGF) appears to confer susceptibility to systemic sclerosis, reported Dr. Carmen Fonseca of Royal Free and University College Medical School, London, and associates.

The researchers genotyped 500 white patients with systemic sclerosis and 500 healthy, white, unrelated control subjects, screening for a specific polymorphism (G-945C) in the region of the CTGF promoter. Significantly more of the patient group (30%) than the control group (19%) carried the polymorphism, they said in the Sept. 20 issue of the New England Journal of Medicine.

There was a strong association between G-allele homozygotes and the presence of specific antibodies—antitopoisomerase 1 and anticentromere—associated with the disease as well as with interstitial lung fibrosis. Positivity for anticentromere antibody previously has been linked to vascular complications such as isolated pulmonary arterial hypertension, which suggests that “a second mechanism involving CTGF overexpression is playing a role” in systemic sclerosis, they said.

“The effects of CTGF on cell proliferation or extracellular matrix production, if induced within certain vessels, could be plausible explanation for this association,” Dr. Fonseca wrote (N. Engl. J. Med. 2207;357:1210–20).

“Our data clearly show an association between the G-945C polymorphism in CTGF and systemic sclerosis, which renders CTGF a susceptibility gene for this complex disease,” they added.

“These data provide new insight into the pathogenesis of systemic sclerosis, including clues to the mechanisms leading to specific disease subtypes. Moreover, they may also be relevant to mechanisms underlying a wide range of other human disorders with a fibrotic component,” Dr. Fonseca and her associates said.

A variation in the promoter region of the gene that encodes connective-tissue growth factor (CTGF) appears to confer susceptibility to systemic sclerosis, reported Dr. Carmen Fonseca of Royal Free and University College Medical School, London, and associates.

The researchers genotyped 500 white patients with systemic sclerosis and 500 healthy, white, unrelated control subjects, screening for a specific polymorphism (G-945C) in the region of the CTGF promoter. Significantly more of the patient group (30%) than the control group (19%) carried the polymorphism, they said in the Sept. 20 issue of the New England Journal of Medicine.

There was a strong association between G-allele homozygotes and the presence of specific antibodies—antitopoisomerase 1 and anticentromere—associated with the disease as well as with interstitial lung fibrosis. Positivity for anticentromere antibody previously has been linked to vascular complications such as isolated pulmonary arterial hypertension, which suggests that “a second mechanism involving CTGF overexpression is playing a role” in systemic sclerosis, they said.

“The effects of CTGF on cell proliferation or extracellular matrix production, if induced within certain vessels, could be plausible explanation for this association,” Dr. Fonseca wrote (N. Engl. J. Med. 2207;357:1210–20).

“Our data clearly show an association between the G-945C polymorphism in CTGF and systemic sclerosis, which renders CTGF a susceptibility gene for this complex disease,” they added.

“These data provide new insight into the pathogenesis of systemic sclerosis, including clues to the mechanisms leading to specific disease subtypes. Moreover, they may also be relevant to mechanisms underlying a wide range of other human disorders with a fibrotic component,” Dr. Fonseca and her associates said.

A variation in the promoter region of the gene that encodes connective-tissue growth factor (CTGF) appears to confer susceptibility to systemic sclerosis, reported Dr. Carmen Fonseca of Royal Free and University College Medical School, London, and associates.

The researchers genotyped 500 white patients with systemic sclerosis and 500 healthy, white, unrelated control subjects, screening for a specific polymorphism (G-945C) in the region of the CTGF promoter. Significantly more of the patient group (30%) than the control group (19%) carried the polymorphism, they said in the Sept. 20 issue of the New England Journal of Medicine.

There was a strong association between G-allele homozygotes and the presence of specific antibodies—antitopoisomerase 1 and anticentromere—associated with the disease as well as with interstitial lung fibrosis. Positivity for anticentromere antibody previously has been linked to vascular complications such as isolated pulmonary arterial hypertension, which suggests that “a second mechanism involving CTGF overexpression is playing a role” in systemic sclerosis, they said.

“The effects of CTGF on cell proliferation or extracellular matrix production, if induced within certain vessels, could be plausible explanation for this association,” Dr. Fonseca wrote (N. Engl. J. Med. 2207;357:1210–20).

“Our data clearly show an association between the G-945C polymorphism in CTGF and systemic sclerosis, which renders CTGF a susceptibility gene for this complex disease,” they added.

“These data provide new insight into the pathogenesis of systemic sclerosis, including clues to the mechanisms leading to specific disease subtypes. Moreover, they may also be relevant to mechanisms underlying a wide range of other human disorders with a fibrotic component,” Dr. Fonseca and her associates said.

True acupuncture and sham acupuncture both were much more effective against chronic low-back pain than was conventional treatment in a large clinical trial comparing the three approaches.

Almost half the subjects who received real or sham acupuncture for 6 months showed clinically relevant improvement in pain intensity or back-specific disability, versus one-fourth of the subjects who received a variety of conventional therapies, investigators in the German Acupuncture (GERAC) Trials reported. (See box.)

“To our knowledge, [this] study is the largest and most rigorous trial to investigate the efficacy of verum acupuncture for chronic low-back pain compared with sham acupuncture and guideline-based conventional therapy. The study yielded several surprising results,” said Dr. Michael Haake of the University of Regensburg, Bad Abbach, Germany, and his associates.

The study subjects were 1,162 adults with chronic low-back pain who were randomized to conventional treatment or real or sham acupuncture administered by physicians at 340 outpatient practices. The study physicians belonged to various medical specialties, had at least 140 hours of acupuncture training, and had practiced acupuncture for a median of 8 years.

Both types of acupuncture involved at least ten 30-minute sessions, usually twice per week, plus additional sessions if the subjects experienced a 10%–50% reduction in pain intensity. The two treatments were identical, except that the sham procedure avoided all known acupuncture points or meridians and involved only superficial insertion of the needles, without any manual stimulation. Subjects were unable to distinguish any difference.

Conventional therapies included at least 10 30-minute sessions with a physician or physiotherapist. Treating physicians were free to administer any combination of techniques, including physiotherapy, massage, heat therapy, electrotherapy, injections, analgesics, anti-inflammatory agents, yoga, hydrojet treatment, exercise, and patient education about managing back pain.

True acupuncture and sham acupuncture were found to be equally effective, as well as more effective than conventional therapies, in relieving pain, improving function, and improving quality of life. All the improvements were significant and persisted long after treatment was completed.

“While all randomized trials and meta-analyses to date have failed to show a clear advantage of acupuncture over conventional therapy for chronic low-back pain, our findings demonstrate significant superiority,” the investigators said (Arch. Intern. Med. 2007;167:1892–8).

Largely on the basis of these results, the German Federal Joint Committee of Physicians and Health Insurance Plans—an agency like the U.S. National Institutes of Health—made acupuncture for low-back pain an insured benefit in that country.

The investigators' finding “forces us to question the underlying action mechanism of acupuncture and to ask whether the emphasis placed on learning the traditional Chinese acupuncture points may be superfluous,” Dr. Haake added.

“The superiority of both forms of acupuncture suggests a common underlying mechanism that may act on pain generation, transmission of pain signals, or processing of pain signals by the central nervous system and that is stronger than the action mechanism of conventional therapy,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

True acupuncture and sham acupuncture both were much more effective against chronic low-back pain than was conventional treatment in a large clinical trial comparing the three approaches.

Almost half the subjects who received real or sham acupuncture for 6 months showed clinically relevant improvement in pain intensity or back-specific disability, versus one-fourth of the subjects who received a variety of conventional therapies, investigators in the German Acupuncture (GERAC) Trials reported. (See box.)

“To our knowledge, [this] study is the largest and most rigorous trial to investigate the efficacy of verum acupuncture for chronic low-back pain compared with sham acupuncture and guideline-based conventional therapy. The study yielded several surprising results,” said Dr. Michael Haake of the University of Regensburg, Bad Abbach, Germany, and his associates.

The study subjects were 1,162 adults with chronic low-back pain who were randomized to conventional treatment or real or sham acupuncture administered by physicians at 340 outpatient practices. The study physicians belonged to various medical specialties, had at least 140 hours of acupuncture training, and had practiced acupuncture for a median of 8 years.

Both types of acupuncture involved at least ten 30-minute sessions, usually twice per week, plus additional sessions if the subjects experienced a 10%–50% reduction in pain intensity. The two treatments were identical, except that the sham procedure avoided all known acupuncture points or meridians and involved only superficial insertion of the needles, without any manual stimulation. Subjects were unable to distinguish any difference.

Conventional therapies included at least 10 30-minute sessions with a physician or physiotherapist. Treating physicians were free to administer any combination of techniques, including physiotherapy, massage, heat therapy, electrotherapy, injections, analgesics, anti-inflammatory agents, yoga, hydrojet treatment, exercise, and patient education about managing back pain.

True acupuncture and sham acupuncture were found to be equally effective, as well as more effective than conventional therapies, in relieving pain, improving function, and improving quality of life. All the improvements were significant and persisted long after treatment was completed.

“While all randomized trials and meta-analyses to date have failed to show a clear advantage of acupuncture over conventional therapy for chronic low-back pain, our findings demonstrate significant superiority,” the investigators said (Arch. Intern. Med. 2007;167:1892–8).

Largely on the basis of these results, the German Federal Joint Committee of Physicians and Health Insurance Plans—an agency like the U.S. National Institutes of Health—made acupuncture for low-back pain an insured benefit in that country.

The investigators' finding “forces us to question the underlying action mechanism of acupuncture and to ask whether the emphasis placed on learning the traditional Chinese acupuncture points may be superfluous,” Dr. Haake added.

“The superiority of both forms of acupuncture suggests a common underlying mechanism that may act on pain generation, transmission of pain signals, or processing of pain signals by the central nervous system and that is stronger than the action mechanism of conventional therapy,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

True acupuncture and sham acupuncture both were much more effective against chronic low-back pain than was conventional treatment in a large clinical trial comparing the three approaches.

Almost half the subjects who received real or sham acupuncture for 6 months showed clinically relevant improvement in pain intensity or back-specific disability, versus one-fourth of the subjects who received a variety of conventional therapies, investigators in the German Acupuncture (GERAC) Trials reported. (See box.)

“To our knowledge, [this] study is the largest and most rigorous trial to investigate the efficacy of verum acupuncture for chronic low-back pain compared with sham acupuncture and guideline-based conventional therapy. The study yielded several surprising results,” said Dr. Michael Haake of the University of Regensburg, Bad Abbach, Germany, and his associates.

The study subjects were 1,162 adults with chronic low-back pain who were randomized to conventional treatment or real or sham acupuncture administered by physicians at 340 outpatient practices. The study physicians belonged to various medical specialties, had at least 140 hours of acupuncture training, and had practiced acupuncture for a median of 8 years.

Both types of acupuncture involved at least ten 30-minute sessions, usually twice per week, plus additional sessions if the subjects experienced a 10%–50% reduction in pain intensity. The two treatments were identical, except that the sham procedure avoided all known acupuncture points or meridians and involved only superficial insertion of the needles, without any manual stimulation. Subjects were unable to distinguish any difference.

Conventional therapies included at least 10 30-minute sessions with a physician or physiotherapist. Treating physicians were free to administer any combination of techniques, including physiotherapy, massage, heat therapy, electrotherapy, injections, analgesics, anti-inflammatory agents, yoga, hydrojet treatment, exercise, and patient education about managing back pain.

True acupuncture and sham acupuncture were found to be equally effective, as well as more effective than conventional therapies, in relieving pain, improving function, and improving quality of life. All the improvements were significant and persisted long after treatment was completed.

“While all randomized trials and meta-analyses to date have failed to show a clear advantage of acupuncture over conventional therapy for chronic low-back pain, our findings demonstrate significant superiority,” the investigators said (Arch. Intern. Med. 2007;167:1892–8).

Largely on the basis of these results, the German Federal Joint Committee of Physicians and Health Insurance Plans—an agency like the U.S. National Institutes of Health—made acupuncture for low-back pain an insured benefit in that country.

The investigators' finding “forces us to question the underlying action mechanism of acupuncture and to ask whether the emphasis placed on learning the traditional Chinese acupuncture points may be superfluous,” Dr. Haake added.

“The superiority of both forms of acupuncture suggests a common underlying mechanism that may act on pain generation, transmission of pain signals, or processing of pain signals by the central nervous system and that is stronger than the action mechanism of conventional therapy,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

Colorectal neoplasms are nearly twice as common in patients newly diagnosed as having coronary artery disease than in those found not to have CAD based on coronary angiography, results of a cross-sectional study suggest.

The prevalence of colorectal neoplasms in patients with CAD in their study was nearly three times as high as that reported in the general population in either Hong Kong or the United States, study investigators reported.

Dr. Annie On On Chan of the University of Hong Kong and her associates previously published a retrospective study showing a strong association between colorectal neoplasms and CAD. To further examine this link, they conducted a cross-sectional study of consecutive patients who were undergoing coronary angiography to assess suspected CAD, followed by colonoscopy.

In industrialized Hong Kong, the incidence rates of colorectal cancer and CAD, and the mortality rates from the conditions, are similar to the rates in Western countries, they noted.

The study included 206 patients who were found to have CAD, 208 patients who were found not to have CAD, and a control group of 207 people from the general Hong Kong population who were matched to the other subjects based on age and sex. The family histories were similar among the groups.

Colonoscopy revealed that colorectal neoplasms were much more prevalent in the CAD-positive group (34%) than in either the CAD-negative group (18%) or the control group (20%).

This 34% prevalence in patients newly diagnosed as having CAD was especially “remarkable,” compared with the current prevalences reported in the general population in Hong Kong (12%) and the United States (10%), Dr. Chan and her associates said (JAMA 2007;298:1412–9).

Similarly, the prevalences of advanced colorectal lesions (18%) and adenocarcinomas (4%) were much higher in the patients with CAD than in the patients who didn't have CAD (6% and 0.5%, respectively) or the control subjects (5% and 1%, respectively).

The reason for this association between CAD and colorectal neoplasm is not yet known, but it is possible that the two disorders share common environmental risk factors. Both disorders have been linked to the metabolic syndrome and smoking, and both “probably develop through the mechanism of chronic inflammation,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

Colorectal neoplasms are nearly twice as common in patients newly diagnosed as having coronary artery disease than in those found not to have CAD based on coronary angiography, results of a cross-sectional study suggest.

The prevalence of colorectal neoplasms in patients with CAD in their study was nearly three times as high as that reported in the general population in either Hong Kong or the United States, study investigators reported.

Dr. Annie On On Chan of the University of Hong Kong and her associates previously published a retrospective study showing a strong association between colorectal neoplasms and CAD. To further examine this link, they conducted a cross-sectional study of consecutive patients who were undergoing coronary angiography to assess suspected CAD, followed by colonoscopy.

In industrialized Hong Kong, the incidence rates of colorectal cancer and CAD, and the mortality rates from the conditions, are similar to the rates in Western countries, they noted.

The study included 206 patients who were found to have CAD, 208 patients who were found not to have CAD, and a control group of 207 people from the general Hong Kong population who were matched to the other subjects based on age and sex. The family histories were similar among the groups.

Colonoscopy revealed that colorectal neoplasms were much more prevalent in the CAD-positive group (34%) than in either the CAD-negative group (18%) or the control group (20%).

This 34% prevalence in patients newly diagnosed as having CAD was especially “remarkable,” compared with the current prevalences reported in the general population in Hong Kong (12%) and the United States (10%), Dr. Chan and her associates said (JAMA 2007;298:1412–9).

Similarly, the prevalences of advanced colorectal lesions (18%) and adenocarcinomas (4%) were much higher in the patients with CAD than in the patients who didn't have CAD (6% and 0.5%, respectively) or the control subjects (5% and 1%, respectively).

The reason for this association between CAD and colorectal neoplasm is not yet known, but it is possible that the two disorders share common environmental risk factors. Both disorders have been linked to the metabolic syndrome and smoking, and both “probably develop through the mechanism of chronic inflammation,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

Colorectal neoplasms are nearly twice as common in patients newly diagnosed as having coronary artery disease than in those found not to have CAD based on coronary angiography, results of a cross-sectional study suggest.

The prevalence of colorectal neoplasms in patients with CAD in their study was nearly three times as high as that reported in the general population in either Hong Kong or the United States, study investigators reported.

Dr. Annie On On Chan of the University of Hong Kong and her associates previously published a retrospective study showing a strong association between colorectal neoplasms and CAD. To further examine this link, they conducted a cross-sectional study of consecutive patients who were undergoing coronary angiography to assess suspected CAD, followed by colonoscopy.

In industrialized Hong Kong, the incidence rates of colorectal cancer and CAD, and the mortality rates from the conditions, are similar to the rates in Western countries, they noted.

The study included 206 patients who were found to have CAD, 208 patients who were found not to have CAD, and a control group of 207 people from the general Hong Kong population who were matched to the other subjects based on age and sex. The family histories were similar among the groups.

Colonoscopy revealed that colorectal neoplasms were much more prevalent in the CAD-positive group (34%) than in either the CAD-negative group (18%) or the control group (20%).

This 34% prevalence in patients newly diagnosed as having CAD was especially “remarkable,” compared with the current prevalences reported in the general population in Hong Kong (12%) and the United States (10%), Dr. Chan and her associates said (JAMA 2007;298:1412–9).

Similarly, the prevalences of advanced colorectal lesions (18%) and adenocarcinomas (4%) were much higher in the patients with CAD than in the patients who didn't have CAD (6% and 0.5%, respectively) or the control subjects (5% and 1%, respectively).

The reason for this association between CAD and colorectal neoplasm is not yet known, but it is possible that the two disorders share common environmental risk factors. Both disorders have been linked to the metabolic syndrome and smoking, and both “probably develop through the mechanism of chronic inflammation,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

Researchers have found “a substantial excess” in deaths attributable to suicide and to coronary heart disease among patients who have undergone bariatric surgery, according to a report.

This descriptive study was not designed to ascertain the basis for this excess mortality, but the investigators postulated that the reasons may be connected in part to obesity itself and its attendant comorbidities, which preceded the surgery. Continued obesity, even after substantial weight loss, as well as weight regain, also probably play a role, according to Dr. Bennet I. Omalu of the University of Pittsburgh and his associates.

The researchers reviewed the records of 16,683 bariatric surgeries performed in Pennsylvania on state residents from 1995 through 2004. There were 440 deaths among these patients, for an overall mortality of 2.6%. Age- and sex-specific death rates were substantially higher than those for the general population, even after procedure-related deaths were excluded from the analysis.

Coronary heart disease was the leading cause of death, accounting for about 20% of deaths that occurred 30 days or more after the procedure. “In the group aged 45–54 years, the CHD mortality rate for women after bariatric surgery was 15.2/10,000 person-years, compared with the rate of similarly aged women in Pennsylvania of 5.46/10, 000,” Dr. Omalu and his associates wrote (Arch. Surg. 2007;142:923–8).

There were 16 deaths (4%) from suicide and 14 (3%) from drug overdoses, some of which may have been misclassified as accidents rather than suicides. Most of these occurred more than a year after the surgery, “suggesting that careful follow-up, especially the need to recognize and treat depression, should be provided,” the investigators noted.

Researchers have found “a substantial excess” in deaths attributable to suicide and to coronary heart disease among patients who have undergone bariatric surgery, according to a report.

This descriptive study was not designed to ascertain the basis for this excess mortality, but the investigators postulated that the reasons may be connected in part to obesity itself and its attendant comorbidities, which preceded the surgery. Continued obesity, even after substantial weight loss, as well as weight regain, also probably play a role, according to Dr. Bennet I. Omalu of the University of Pittsburgh and his associates.

The researchers reviewed the records of 16,683 bariatric surgeries performed in Pennsylvania on state residents from 1995 through 2004. There were 440 deaths among these patients, for an overall mortality of 2.6%. Age- and sex-specific death rates were substantially higher than those for the general population, even after procedure-related deaths were excluded from the analysis.

Coronary heart disease was the leading cause of death, accounting for about 20% of deaths that occurred 30 days or more after the procedure. “In the group aged 45–54 years, the CHD mortality rate for women after bariatric surgery was 15.2/10,000 person-years, compared with the rate of similarly aged women in Pennsylvania of 5.46/10, 000,” Dr. Omalu and his associates wrote (Arch. Surg. 2007;142:923–8).

There were 16 deaths (4%) from suicide and 14 (3%) from drug overdoses, some of which may have been misclassified as accidents rather than suicides. Most of these occurred more than a year after the surgery, “suggesting that careful follow-up, especially the need to recognize and treat depression, should be provided,” the investigators noted.

Researchers have found “a substantial excess” in deaths attributable to suicide and to coronary heart disease among patients who have undergone bariatric surgery, according to a report.

This descriptive study was not designed to ascertain the basis for this excess mortality, but the investigators postulated that the reasons may be connected in part to obesity itself and its attendant comorbidities, which preceded the surgery. Continued obesity, even after substantial weight loss, as well as weight regain, also probably play a role, according to Dr. Bennet I. Omalu of the University of Pittsburgh and his associates.

The researchers reviewed the records of 16,683 bariatric surgeries performed in Pennsylvania on state residents from 1995 through 2004. There were 440 deaths among these patients, for an overall mortality of 2.6%. Age- and sex-specific death rates were substantially higher than those for the general population, even after procedure-related deaths were excluded from the analysis.

Coronary heart disease was the leading cause of death, accounting for about 20% of deaths that occurred 30 days or more after the procedure. “In the group aged 45–54 years, the CHD mortality rate for women after bariatric surgery was 15.2/10,000 person-years, compared with the rate of similarly aged women in Pennsylvania of 5.46/10, 000,” Dr. Omalu and his associates wrote (Arch. Surg. 2007;142:923–8).

There were 16 deaths (4%) from suicide and 14 (3%) from drug overdoses, some of which may have been misclassified as accidents rather than suicides. Most of these occurred more than a year after the surgery, “suggesting that careful follow-up, especially the need to recognize and treat depression, should be provided,” the investigators noted.