Mary Ann Moon

Testosterone therapy taken for "low T" raises the risk of mortality, myocardial infarction, and ischemic stroke, according to a report published online Nov. 5 in JAMA.

The risk elevation is consistent in both men who have existing coronary artery disease and men who do not, and is not affected by differences in cardiovascular risk factors such as blood pressure or by the use of preventive medications, said Dr. Rebecca Vigen of the University of Texas at Southwestern Medical Center, Dallas, and her associates.

These findings, from what the investigators describe as the first observational study to suggest a causal link between testosterone therapy and adverse cardiovascular outcomes, "raise concerns about the potential safety of testosterone therapy." Randomized clinical trials are warranted to clarify this issue, they noted.

"Although physicians should continue to discuss the symptomatic benefits of testosterone therapy with patients, it is also important to inform patients that long-term risks are unknown and there is a possibility that testosterone therapy might be harmful," Dr. Vigen and her colleagues added.

Previous studies have shown that testosterone therapy improves sexual function and strength, as well as some cardiovascular risk factors such as lipid profiles and insulin resistance. They have not detected adverse CV effects, "but these trials were generally focused on intermediate endpoints, of short duration, and not powered for clinical endpoints," the investigators wrote.

One clinical trial that included many men with CV disorders was halted early in 2010 when the group receiving testosterone was found to have an excess of CV events, compared with the placebo group.

Dr. Vigen and her associates examined the potential CV risks of testosterone therapy in a retrospective cohort study using data from the Veterans Administration’s Clinical Assessment Reporting and Tracking (CART) program, which collects information on all procedures performed in the 76 VA cardiac catheterization laboratories across the country. They identified all men who underwent coronary angiography at these facilities in 2005-2011 (who therefore had well-characterized cardiovascular profiles) and whose medical records also showed a total testosterone level of less than 300 ng/dL.

This cohort of 8,709 men had a high burden of comorbidities: 20% had a history of MI, half had diabetes, and more than 80% had coronary artery disease. Rates of these comorbidities were approximately equal between men taking testosterone and men not taking testosterone.

A total of 1,223 of these men were taking testosterone therapy to address their low testosterone levels. Roughly 1% of them were using testosterone gel, 36% were using injections, and 63% were using patches. Men who used testosterone tended to be younger and healthier than those who did not.

During an average of 28 months of follow-up, there were 1,710 adverse events of interest: 748 men died, 443 had MIs, and 519 had strokes. The absolute risk of these events was significantly greater in testosterone users than in nonusers: 1.3% higher at 1 year, 3.1% higher at 2 years, and 5.8% higher at 3 years, the investigators said (JAMA 2013 [doi:10.1001/jama2013.280386]).

In a further, adjusted analysis of the data, testosterone use remained strongly associated with increased risk of death, MI, or stroke, with a hazard ratio of 1.29. This indicates that testosterone users were 29% more likely than were nonusers to experience these adverse outcomes.

These findings were unchanged after the data were further adjusted to account for the presence or absence of CAD and the use or nonuse of coronary revascularization procedures.

There was no significant difference in risk of adverse outcomes among the three formulations of testosterone.

The researchers noted that there are several potential mechanisms by which testosterone therapy might increase cardiovascular risk. It increases platelet aggregation, which contributes to arterial plaque formation. It enhances monocyte activation in the endothelium, which promotes atherosclerosis and is implicated in the pathogenesis of acute coronary syndromes. And it aggravates sleep-disordered breathing, another CV risk factor, they said.

This study was supported by the U.S. Department of Veterans Affairs. No financial conflicts of interest were reported.

Testosterone therapy taken for "low T" raises the risk of mortality, myocardial infarction, and ischemic stroke, according to a report published online Nov. 5 in JAMA.

The risk elevation is consistent in both men who have existing coronary artery disease and men who do not, and is not affected by differences in cardiovascular risk factors such as blood pressure or by the use of preventive medications, said Dr. Rebecca Vigen of the University of Texas at Southwestern Medical Center, Dallas, and her associates.

These findings, from what the investigators describe as the first observational study to suggest a causal link between testosterone therapy and adverse cardiovascular outcomes, "raise concerns about the potential safety of testosterone therapy." Randomized clinical trials are warranted to clarify this issue, they noted.

"Although physicians should continue to discuss the symptomatic benefits of testosterone therapy with patients, it is also important to inform patients that long-term risks are unknown and there is a possibility that testosterone therapy might be harmful," Dr. Vigen and her colleagues added.

Previous studies have shown that testosterone therapy improves sexual function and strength, as well as some cardiovascular risk factors such as lipid profiles and insulin resistance. They have not detected adverse CV effects, "but these trials were generally focused on intermediate endpoints, of short duration, and not powered for clinical endpoints," the investigators wrote.

One clinical trial that included many men with CV disorders was halted early in 2010 when the group receiving testosterone was found to have an excess of CV events, compared with the placebo group.

Dr. Vigen and her associates examined the potential CV risks of testosterone therapy in a retrospective cohort study using data from the Veterans Administration’s Clinical Assessment Reporting and Tracking (CART) program, which collects information on all procedures performed in the 76 VA cardiac catheterization laboratories across the country. They identified all men who underwent coronary angiography at these facilities in 2005-2011 (who therefore had well-characterized cardiovascular profiles) and whose medical records also showed a total testosterone level of less than 300 ng/dL.

This cohort of 8,709 men had a high burden of comorbidities: 20% had a history of MI, half had diabetes, and more than 80% had coronary artery disease. Rates of these comorbidities were approximately equal between men taking testosterone and men not taking testosterone.

A total of 1,223 of these men were taking testosterone therapy to address their low testosterone levels. Roughly 1% of them were using testosterone gel, 36% were using injections, and 63% were using patches. Men who used testosterone tended to be younger and healthier than those who did not.

During an average of 28 months of follow-up, there were 1,710 adverse events of interest: 748 men died, 443 had MIs, and 519 had strokes. The absolute risk of these events was significantly greater in testosterone users than in nonusers: 1.3% higher at 1 year, 3.1% higher at 2 years, and 5.8% higher at 3 years, the investigators said (JAMA 2013 [doi:10.1001/jama2013.280386]).

In a further, adjusted analysis of the data, testosterone use remained strongly associated with increased risk of death, MI, or stroke, with a hazard ratio of 1.29. This indicates that testosterone users were 29% more likely than were nonusers to experience these adverse outcomes.

These findings were unchanged after the data were further adjusted to account for the presence or absence of CAD and the use or nonuse of coronary revascularization procedures.

There was no significant difference in risk of adverse outcomes among the three formulations of testosterone.

The researchers noted that there are several potential mechanisms by which testosterone therapy might increase cardiovascular risk. It increases platelet aggregation, which contributes to arterial plaque formation. It enhances monocyte activation in the endothelium, which promotes atherosclerosis and is implicated in the pathogenesis of acute coronary syndromes. And it aggravates sleep-disordered breathing, another CV risk factor, they said.

This study was supported by the U.S. Department of Veterans Affairs. No financial conflicts of interest were reported.

Testosterone therapy taken for "low T" raises the risk of mortality, myocardial infarction, and ischemic stroke, according to a report published online Nov. 5 in JAMA.

The risk elevation is consistent in both men who have existing coronary artery disease and men who do not, and is not affected by differences in cardiovascular risk factors such as blood pressure or by the use of preventive medications, said Dr. Rebecca Vigen of the University of Texas at Southwestern Medical Center, Dallas, and her associates.

These findings, from what the investigators describe as the first observational study to suggest a causal link between testosterone therapy and adverse cardiovascular outcomes, "raise concerns about the potential safety of testosterone therapy." Randomized clinical trials are warranted to clarify this issue, they noted.

"Although physicians should continue to discuss the symptomatic benefits of testosterone therapy with patients, it is also important to inform patients that long-term risks are unknown and there is a possibility that testosterone therapy might be harmful," Dr. Vigen and her colleagues added.

Previous studies have shown that testosterone therapy improves sexual function and strength, as well as some cardiovascular risk factors such as lipid profiles and insulin resistance. They have not detected adverse CV effects, "but these trials were generally focused on intermediate endpoints, of short duration, and not powered for clinical endpoints," the investigators wrote.

One clinical trial that included many men with CV disorders was halted early in 2010 when the group receiving testosterone was found to have an excess of CV events, compared with the placebo group.

Dr. Vigen and her associates examined the potential CV risks of testosterone therapy in a retrospective cohort study using data from the Veterans Administration’s Clinical Assessment Reporting and Tracking (CART) program, which collects information on all procedures performed in the 76 VA cardiac catheterization laboratories across the country. They identified all men who underwent coronary angiography at these facilities in 2005-2011 (who therefore had well-characterized cardiovascular profiles) and whose medical records also showed a total testosterone level of less than 300 ng/dL.

This cohort of 8,709 men had a high burden of comorbidities: 20% had a history of MI, half had diabetes, and more than 80% had coronary artery disease. Rates of these comorbidities were approximately equal between men taking testosterone and men not taking testosterone.

A total of 1,223 of these men were taking testosterone therapy to address their low testosterone levels. Roughly 1% of them were using testosterone gel, 36% were using injections, and 63% were using patches. Men who used testosterone tended to be younger and healthier than those who did not.

During an average of 28 months of follow-up, there were 1,710 adverse events of interest: 748 men died, 443 had MIs, and 519 had strokes. The absolute risk of these events was significantly greater in testosterone users than in nonusers: 1.3% higher at 1 year, 3.1% higher at 2 years, and 5.8% higher at 3 years, the investigators said (JAMA 2013 [doi:10.1001/jama2013.280386]).

In a further, adjusted analysis of the data, testosterone use remained strongly associated with increased risk of death, MI, or stroke, with a hazard ratio of 1.29. This indicates that testosterone users were 29% more likely than were nonusers to experience these adverse outcomes.

These findings were unchanged after the data were further adjusted to account for the presence or absence of CAD and the use or nonuse of coronary revascularization procedures.

There was no significant difference in risk of adverse outcomes among the three formulations of testosterone.

The researchers noted that there are several potential mechanisms by which testosterone therapy might increase cardiovascular risk. It increases platelet aggregation, which contributes to arterial plaque formation. It enhances monocyte activation in the endothelium, which promotes atherosclerosis and is implicated in the pathogenesis of acute coronary syndromes. And it aggravates sleep-disordered breathing, another CV risk factor, they said.

This study was supported by the U.S. Department of Veterans Affairs. No financial conflicts of interest were reported.

For patients with chronic hepatitis C infection, achieving an undetectable viral load cut the risk of death by 45% and the risk of liver-related adverse events by 27%, a large study demonstrated.

But only 16% of patients who took antivirals reached undetectable viral levels, according to the first cohort study to quantify the impact of viral load–suppression on real-world patients at all levels of disease progression.

Bristol-Myers Squibb sponsored the trial, and its findings were simultaneously presented at the annual meeting of the American Association for the Study of Liver Diseases and published online Nov. 5 in JAMA Internal Medicine.

Unfortunately, very few patients achieve an undetectable viral load without taking antiviral agents – only 39 of 97,485 untreated participants in the study. And because of the drugs’ adverse effects and expense, only one-fourth of patients in real-world clinical conditions are willing to initiate antiviral therapy – and only a fraction of those treated patients (16.4% in the study) achieved viral suppression to undetectable levels, said Jeffrey McCombs, Ph.D., of the department of clinical pharmacy and pharmaceutical economics and policy, University of Southern California, Los Angeles, and his associates.

To obtain a cohort large enough to quantify the effects of viral load suppression, Dr. McCombs and his colleagues used information from the Veterans Affairs clinical case registry of HCV-infected patients. They identified and examined the clinical records of 128,769 patients enrolled in the database in 1999-2010. The mean follow-up period was 6 years.

Those study subjects were predominantly men, and the mean age was 52 years. Approximately 51% were white, and 31% were black.

Only 24.3% of the total study population received antiviral therapy at any time after diagnosis, and only 16.4% achieved an undetectable viral load after treatment.

The study’s coprimary endpoints were all-cause mortality and a composite of newly diagnosed cirrhosis (either compensated or decompensated), hepatocellular carcinoma, or a liver-related hospitalization. There were 15,458 deaths and 35,253 composite events in the sample of 734,829 person-years of data.

Compared with the majority of patients who carried a detectable viral load throughout the study period, patients who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint, the investigators said (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12505]).

Achieving an undetectable viral load also reduced the risk of each component of the composite endpoint, individually.

The results remained very robust in a sensitivity analysis restricted only to the 54,420 patients who had significant liver fibrosis at baseline.

"Clearly, new therapeutic options might offer significant benefits ... if their introduction improves the willingness of patients to initiate therapy and the likelihood that the patient will achieve viral suppression leading to a sustained viral response," Dr. McCombs and his associates said.

Understanding the challenges patients face with those treatments, as well as patient expectations, "are essential to help both providers and patients make informed decisions about when to initiate antiviral therapy and to motivate patient adherence," the researchers added.

Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.

For patients with chronic hepatitis C infection, achieving an undetectable viral load cut the risk of death by 45% and the risk of liver-related adverse events by 27%, a large study demonstrated.

But only 16% of patients who took antivirals reached undetectable viral levels, according to the first cohort study to quantify the impact of viral load–suppression on real-world patients at all levels of disease progression.

Bristol-Myers Squibb sponsored the trial, and its findings were simultaneously presented at the annual meeting of the American Association for the Study of Liver Diseases and published online Nov. 5 in JAMA Internal Medicine.

Unfortunately, very few patients achieve an undetectable viral load without taking antiviral agents – only 39 of 97,485 untreated participants in the study. And because of the drugs’ adverse effects and expense, only one-fourth of patients in real-world clinical conditions are willing to initiate antiviral therapy – and only a fraction of those treated patients (16.4% in the study) achieved viral suppression to undetectable levels, said Jeffrey McCombs, Ph.D., of the department of clinical pharmacy and pharmaceutical economics and policy, University of Southern California, Los Angeles, and his associates.

To obtain a cohort large enough to quantify the effects of viral load suppression, Dr. McCombs and his colleagues used information from the Veterans Affairs clinical case registry of HCV-infected patients. They identified and examined the clinical records of 128,769 patients enrolled in the database in 1999-2010. The mean follow-up period was 6 years.

Those study subjects were predominantly men, and the mean age was 52 years. Approximately 51% were white, and 31% were black.

Only 24.3% of the total study population received antiviral therapy at any time after diagnosis, and only 16.4% achieved an undetectable viral load after treatment.

The study’s coprimary endpoints were all-cause mortality and a composite of newly diagnosed cirrhosis (either compensated or decompensated), hepatocellular carcinoma, or a liver-related hospitalization. There were 15,458 deaths and 35,253 composite events in the sample of 734,829 person-years of data.

Compared with the majority of patients who carried a detectable viral load throughout the study period, patients who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint, the investigators said (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12505]).

Achieving an undetectable viral load also reduced the risk of each component of the composite endpoint, individually.

The results remained very robust in a sensitivity analysis restricted only to the 54,420 patients who had significant liver fibrosis at baseline.

"Clearly, new therapeutic options might offer significant benefits ... if their introduction improves the willingness of patients to initiate therapy and the likelihood that the patient will achieve viral suppression leading to a sustained viral response," Dr. McCombs and his associates said.

Understanding the challenges patients face with those treatments, as well as patient expectations, "are essential to help both providers and patients make informed decisions about when to initiate antiviral therapy and to motivate patient adherence," the researchers added.

Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.

For patients with chronic hepatitis C infection, achieving an undetectable viral load cut the risk of death by 45% and the risk of liver-related adverse events by 27%, a large study demonstrated.

But only 16% of patients who took antivirals reached undetectable viral levels, according to the first cohort study to quantify the impact of viral load–suppression on real-world patients at all levels of disease progression.

Bristol-Myers Squibb sponsored the trial, and its findings were simultaneously presented at the annual meeting of the American Association for the Study of Liver Diseases and published online Nov. 5 in JAMA Internal Medicine.

Unfortunately, very few patients achieve an undetectable viral load without taking antiviral agents – only 39 of 97,485 untreated participants in the study. And because of the drugs’ adverse effects and expense, only one-fourth of patients in real-world clinical conditions are willing to initiate antiviral therapy – and only a fraction of those treated patients (16.4% in the study) achieved viral suppression to undetectable levels, said Jeffrey McCombs, Ph.D., of the department of clinical pharmacy and pharmaceutical economics and policy, University of Southern California, Los Angeles, and his associates.

To obtain a cohort large enough to quantify the effects of viral load suppression, Dr. McCombs and his colleagues used information from the Veterans Affairs clinical case registry of HCV-infected patients. They identified and examined the clinical records of 128,769 patients enrolled in the database in 1999-2010. The mean follow-up period was 6 years.

Those study subjects were predominantly men, and the mean age was 52 years. Approximately 51% were white, and 31% were black.

Only 24.3% of the total study population received antiviral therapy at any time after diagnosis, and only 16.4% achieved an undetectable viral load after treatment.

The study’s coprimary endpoints were all-cause mortality and a composite of newly diagnosed cirrhosis (either compensated or decompensated), hepatocellular carcinoma, or a liver-related hospitalization. There were 15,458 deaths and 35,253 composite events in the sample of 734,829 person-years of data.

Compared with the majority of patients who carried a detectable viral load throughout the study period, patients who achieved an undetectable viral load showed a 45% lower risk of death and a 27% lower risk of the composite endpoint, the investigators said (JAMA Intern. Med. 2013 Nov. 5 [doi:10.1001/jamainternmed.2013.12505]).

Achieving an undetectable viral load also reduced the risk of each component of the composite endpoint, individually.

The results remained very robust in a sensitivity analysis restricted only to the 54,420 patients who had significant liver fibrosis at baseline.

"Clearly, new therapeutic options might offer significant benefits ... if their introduction improves the willingness of patients to initiate therapy and the likelihood that the patient will achieve viral suppression leading to a sustained viral response," Dr. McCombs and his associates said.

Understanding the challenges patients face with those treatments, as well as patient expectations, "are essential to help both providers and patients make informed decisions about when to initiate antiviral therapy and to motivate patient adherence," the researchers added.

Bristol-Myers Squibb supported the study. Dr. McCombs and his associates also reported other ties to Bristol-Myers Squibb.

Atrial fibrillation is strongly associated with incident myocardial infarction, independently of coronary risk factors and potential confounders, according to an analysis of data from the REGARDS study published online Nov. 4 in JAMA.

In a cohort study involving nearly 24,000 adults in the general population, those who had AF at baseline were twice as likely to develop MI during the ensuing 7 years of follow-up as were those without AF. The increased risk conferred by AF was significantly stronger among women and blacks than among men and whites, reported Dr. Elsayed Z. Soliman of the Epidemiological Cardiology Research Center, Wake Forest University, Winston-Salem, N.C., and his associates.

"These findings add to the growing concerns of the seriousness of AF as a public health burden: In addition to being a well-known risk factor for stroke, it is also associated with increased risk of MI," they said.

This is the first report of such an association, the investigators noted.

MI is known to be a risk factor for AF, and recent research has suggested that the converse may also be true. But to date there has been little evidence from population studies to support this assertion.

Dr. Soliman and his colleagues examined the issue in a secondary analysis of data from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, a large biracial, population-based cohort study of the causes of regional and racial disparities in stroke mortality. REGARDS assessed more than 30,000 adults residing in the "stroke belt" of the southeastern United States, carefully characterizing their cardiovascular risk and rigorously adjudicating incident MIs during up to 7 years of close follow-up (median follow-up, 4.5 years).

For their analysis, Dr. Soliman and his associates studied the records of a subset of 23,928 participants who had no coronary heart disease (CHD) at baseline and whose atrial fibrillation status was known. There were 1,631 study subjects who had already been diagnosed as having AF or who were found to have AF on baseline ECG.

A total of 648 MIs occurred during follow-up.

The age-adjusted incidence of MI was 12 per 1,000 in participants who had AF, compared with 6 per 1,000 in participants who didn\'t have AF, the researchers reported (JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11912]).

In a further analysis that adjusted for numerous sociodemographic factors, AF was associated with a 96% increase in MI risk, compared with no AF.

The association between AF and incident MI remained strong after further adjustment for CHD risk factors and numerous potential confounders.

These results indicate a bidirectional relationship between AF and MI, "with each leading to the other. Similar bidirectional relationships between AF and chronic kidney disease and between AF and heart failure have been reported," the researchers said.

In subgroup analyses, this association remained robust regardless of subject age, and was no different between older adults (those over age 65 or 75) and younger adults. However, the association was different according to subject gender and race: It was strongest among black men, less strong but still significant among white women, even less strong but still significant among black women, and nonsignificant among white men.

In addition, the association between AF and incident MI was significantly weaker among participants who were taking warfarin than among those who were not. "This accords with previous reports showing that warfarin might provide a protective effect against MI after acute coronary syndromes and in patients with AF who are prescribed anticoagulation for stroke prevention," the investigators said.

Although this study was not designed to determine why AF appears to raise the risk of incident MI, there are several plausible explanations.

First, both conditions share similar risk factors, so common pathophysiologic processes might underlie both outcomes. "That is, in susceptible individuals, both AF and MI may eventually occur, and it is just a matter of which comes first," Dr. Soliman and his associates said.

Second, subclinical CHD may be associated with a high risk of both AF and MI. Thus, "AF may not be a risk factor for incident MI but rather a marker of prevalent CHD that in turn places individuals at higher risk for MI events," they said.

A third possibility is that AF "creates and sustains an inflammatory and prothrombotic environment," including systemic platelet activation, thrombin generation, endothelial dysfunction, and inflammation, which in turn increase the risk of MI.

Finally, reports have suggested that MI due to coronary embolism actually is more frequent than it is thought to be, and have identified AF as an underlying cause of such emboli. So "coronary embolization, which may not be as rare as we think, could be one of the mechanisms explaining our findings," the investigators said.

The REGARDS study was supported by the National Institutes of Health. Dr. Soliman and his associates reported no financial conflicts of interest.

Atrial fibrillation is strongly associated with incident myocardial infarction, independently of coronary risk factors and potential confounders, according to an analysis of data from the REGARDS study published online Nov. 4 in JAMA.

In a cohort study involving nearly 24,000 adults in the general population, those who had AF at baseline were twice as likely to develop MI during the ensuing 7 years of follow-up as were those without AF. The increased risk conferred by AF was significantly stronger among women and blacks than among men and whites, reported Dr. Elsayed Z. Soliman of the Epidemiological Cardiology Research Center, Wake Forest University, Winston-Salem, N.C., and his associates.

"These findings add to the growing concerns of the seriousness of AF as a public health burden: In addition to being a well-known risk factor for stroke, it is also associated with increased risk of MI," they said.

This is the first report of such an association, the investigators noted.

MI is known to be a risk factor for AF, and recent research has suggested that the converse may also be true. But to date there has been little evidence from population studies to support this assertion.

Dr. Soliman and his colleagues examined the issue in a secondary analysis of data from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, a large biracial, population-based cohort study of the causes of regional and racial disparities in stroke mortality. REGARDS assessed more than 30,000 adults residing in the "stroke belt" of the southeastern United States, carefully characterizing their cardiovascular risk and rigorously adjudicating incident MIs during up to 7 years of close follow-up (median follow-up, 4.5 years).

For their analysis, Dr. Soliman and his associates studied the records of a subset of 23,928 participants who had no coronary heart disease (CHD) at baseline and whose atrial fibrillation status was known. There were 1,631 study subjects who had already been diagnosed as having AF or who were found to have AF on baseline ECG.

A total of 648 MIs occurred during follow-up.

The age-adjusted incidence of MI was 12 per 1,000 in participants who had AF, compared with 6 per 1,000 in participants who didn\'t have AF, the researchers reported (JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11912]).

In a further analysis that adjusted for numerous sociodemographic factors, AF was associated with a 96% increase in MI risk, compared with no AF.

The association between AF and incident MI remained strong after further adjustment for CHD risk factors and numerous potential confounders.

These results indicate a bidirectional relationship between AF and MI, "with each leading to the other. Similar bidirectional relationships between AF and chronic kidney disease and between AF and heart failure have been reported," the researchers said.

In subgroup analyses, this association remained robust regardless of subject age, and was no different between older adults (those over age 65 or 75) and younger adults. However, the association was different according to subject gender and race: It was strongest among black men, less strong but still significant among white women, even less strong but still significant among black women, and nonsignificant among white men.

In addition, the association between AF and incident MI was significantly weaker among participants who were taking warfarin than among those who were not. "This accords with previous reports showing that warfarin might provide a protective effect against MI after acute coronary syndromes and in patients with AF who are prescribed anticoagulation for stroke prevention," the investigators said.

Although this study was not designed to determine why AF appears to raise the risk of incident MI, there are several plausible explanations.

First, both conditions share similar risk factors, so common pathophysiologic processes might underlie both outcomes. "That is, in susceptible individuals, both AF and MI may eventually occur, and it is just a matter of which comes first," Dr. Soliman and his associates said.

Second, subclinical CHD may be associated with a high risk of both AF and MI. Thus, "AF may not be a risk factor for incident MI but rather a marker of prevalent CHD that in turn places individuals at higher risk for MI events," they said.

A third possibility is that AF "creates and sustains an inflammatory and prothrombotic environment," including systemic platelet activation, thrombin generation, endothelial dysfunction, and inflammation, which in turn increase the risk of MI.

Finally, reports have suggested that MI due to coronary embolism actually is more frequent than it is thought to be, and have identified AF as an underlying cause of such emboli. So "coronary embolization, which may not be as rare as we think, could be one of the mechanisms explaining our findings," the investigators said.

The REGARDS study was supported by the National Institutes of Health. Dr. Soliman and his associates reported no financial conflicts of interest.

Atrial fibrillation is strongly associated with incident myocardial infarction, independently of coronary risk factors and potential confounders, according to an analysis of data from the REGARDS study published online Nov. 4 in JAMA.

In a cohort study involving nearly 24,000 adults in the general population, those who had AF at baseline were twice as likely to develop MI during the ensuing 7 years of follow-up as were those without AF. The increased risk conferred by AF was significantly stronger among women and blacks than among men and whites, reported Dr. Elsayed Z. Soliman of the Epidemiological Cardiology Research Center, Wake Forest University, Winston-Salem, N.C., and his associates.

"These findings add to the growing concerns of the seriousness of AF as a public health burden: In addition to being a well-known risk factor for stroke, it is also associated with increased risk of MI," they said.

This is the first report of such an association, the investigators noted.

MI is known to be a risk factor for AF, and recent research has suggested that the converse may also be true. But to date there has been little evidence from population studies to support this assertion.

Dr. Soliman and his colleagues examined the issue in a secondary analysis of data from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, a large biracial, population-based cohort study of the causes of regional and racial disparities in stroke mortality. REGARDS assessed more than 30,000 adults residing in the "stroke belt" of the southeastern United States, carefully characterizing their cardiovascular risk and rigorously adjudicating incident MIs during up to 7 years of close follow-up (median follow-up, 4.5 years).

For their analysis, Dr. Soliman and his associates studied the records of a subset of 23,928 participants who had no coronary heart disease (CHD) at baseline and whose atrial fibrillation status was known. There were 1,631 study subjects who had already been diagnosed as having AF or who were found to have AF on baseline ECG.

A total of 648 MIs occurred during follow-up.

The age-adjusted incidence of MI was 12 per 1,000 in participants who had AF, compared with 6 per 1,000 in participants who didn\'t have AF, the researchers reported (JAMA Intern. Med. 2013 Nov. 4 [doi: 10.1001/jamainternmed.2013.11912]).

In a further analysis that adjusted for numerous sociodemographic factors, AF was associated with a 96% increase in MI risk, compared with no AF.

The association between AF and incident MI remained strong after further adjustment for CHD risk factors and numerous potential confounders.

These results indicate a bidirectional relationship between AF and MI, "with each leading to the other. Similar bidirectional relationships between AF and chronic kidney disease and between AF and heart failure have been reported," the researchers said.

In subgroup analyses, this association remained robust regardless of subject age, and was no different between older adults (those over age 65 or 75) and younger adults. However, the association was different according to subject gender and race: It was strongest among black men, less strong but still significant among white women, even less strong but still significant among black women, and nonsignificant among white men.

In addition, the association between AF and incident MI was significantly weaker among participants who were taking warfarin than among those who were not. "This accords with previous reports showing that warfarin might provide a protective effect against MI after acute coronary syndromes and in patients with AF who are prescribed anticoagulation for stroke prevention," the investigators said.

Although this study was not designed to determine why AF appears to raise the risk of incident MI, there are several plausible explanations.

First, both conditions share similar risk factors, so common pathophysiologic processes might underlie both outcomes. "That is, in susceptible individuals, both AF and MI may eventually occur, and it is just a matter of which comes first," Dr. Soliman and his associates said.

Second, subclinical CHD may be associated with a high risk of both AF and MI. Thus, "AF may not be a risk factor for incident MI but rather a marker of prevalent CHD that in turn places individuals at higher risk for MI events," they said.

A third possibility is that AF "creates and sustains an inflammatory and prothrombotic environment," including systemic platelet activation, thrombin generation, endothelial dysfunction, and inflammation, which in turn increase the risk of MI.

Finally, reports have suggested that MI due to coronary embolism actually is more frequent than it is thought to be, and have identified AF as an underlying cause of such emboli. So "coronary embolization, which may not be as rare as we think, could be one of the mechanisms explaining our findings," the investigators said.

The REGARDS study was supported by the National Institutes of Health. Dr. Soliman and his associates reported no financial conflicts of interest.

Clinicians can expect "substantial" weight loss in severely obese patients 3 years after they undergo Roux-en-Y gastric bypass but less impressive weight loss 3 years after laparoscopic adjustable gastric banding, according to a report published online Nov. 4 in JAMA.

In a multicenter follow-up study of 2,348 such patients, those who underwent Roux-en-Y gastric bypass (RYGB) lost a median of 31.5% of their baseline weight and those who underwent laparoscopic adjustable gastric banding (LAGB) lost a median of 15.9% of their baseline weight at 3 years, said Dr. Anita P. Courcoulas of the department of surgery, University of Pittsburgh Medical Center, and her associates.

"Because our patient population was diverse and our results were from a large number of surgeons and surgical centers, long-term sustained weight loss can be expected from RYGB, and the results are likely generalizable. [However,] weight loss associated with the LAGB procedure was less than anticipated ... and less than what would be expected based on published series," the investigators noted.

Dr. Courcoulas and her colleagues in the Longitudinal Assessment of Bariatric Surgery consortium performed this observational cohort study at 10 hospitals across the United States. A total of 1,738 adults underwent RYGB, and 610 underwent LAGB. The median age was 46 years (range, 18-78 years). Most of the study subjects were women (79%), and 14% were nonwhite.

After 3 years, patients in the RYGB group lost a median of 41 kg (range, 110-kg loss to a 1-kg gain). Most of that loss occurred during the first postsurgical year, and typically there was "mild" weight regain between years 2 and 3.

Patients in the LAGB group lost a median of 20 kg (range, 75-kg loss to a 20-kg gain). Most of that loss also occurred during the first postsurgical year, with less than 20% of patients losing much weight after that. Typically, that weight loss was maintained between years 2 and 3, the investigators said (JAMA 2013 Nov. 4 [doi:10.1001/jama.2013.280928]).

Approximately 67% of patients in the RYGB group had at least partial remission of diabetes at year 3, a percentage similar to that reported in the literature. In contrast, only 27% of those in the LAGB group had at least partial remission of diabetes at year 3, which is a substantially lower rate than the 73% reported in the literature.

At the same time, 0.9% of patients in the RYGB group and 3.2% of those in the LAGB group developed new-onset diabetes during follow-up.

Approximately 62% of the RYGB group had remission of dyslipidemia, while 3.2% developed new-onset dyslipidemia. In contrast, only 27% of the LAGB group had remission of dyslipidemia, while 16% developed new-onset dyslipidemia. The pattern was similar for hyperlipidemia.

Approximately 38% of the RYGB group had remission of hypertension, while 13% developed new-onset hypertension during follow-up. For the LAGB group, the proportion of new-onset cases of hypertension (18.1%) actually exceeded the proportion of remissions (17.4%).

Concerning adverse events, three deaths occurred within 30 days of an RYGB procedure, and two revision procedures and two reversal procedures were required during 3-year follow-up. The corresponding figures for LAGB were zero postsurgical deaths and 77 surgeries to remove the band or revise the surgery during follow-up.

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Courcoulas reported ties to Allergan, Covidien, EndoGastric Solutions, Ethicon J & J Healthcare System, Nutrisystem, and Pfizer, and her associates reported ties to several industry sources.

Clinicians can expect "substantial" weight loss in severely obese patients 3 years after they undergo Roux-en-Y gastric bypass but less impressive weight loss 3 years after laparoscopic adjustable gastric banding, according to a report published online Nov. 4 in JAMA.

In a multicenter follow-up study of 2,348 such patients, those who underwent Roux-en-Y gastric bypass (RYGB) lost a median of 31.5% of their baseline weight and those who underwent laparoscopic adjustable gastric banding (LAGB) lost a median of 15.9% of their baseline weight at 3 years, said Dr. Anita P. Courcoulas of the department of surgery, University of Pittsburgh Medical Center, and her associates.

"Because our patient population was diverse and our results were from a large number of surgeons and surgical centers, long-term sustained weight loss can be expected from RYGB, and the results are likely generalizable. [However,] weight loss associated with the LAGB procedure was less than anticipated ... and less than what would be expected based on published series," the investigators noted.

Dr. Courcoulas and her colleagues in the Longitudinal Assessment of Bariatric Surgery consortium performed this observational cohort study at 10 hospitals across the United States. A total of 1,738 adults underwent RYGB, and 610 underwent LAGB. The median age was 46 years (range, 18-78 years). Most of the study subjects were women (79%), and 14% were nonwhite.

After 3 years, patients in the RYGB group lost a median of 41 kg (range, 110-kg loss to a 1-kg gain). Most of that loss occurred during the first postsurgical year, and typically there was "mild" weight regain between years 2 and 3.

Patients in the LAGB group lost a median of 20 kg (range, 75-kg loss to a 20-kg gain). Most of that loss also occurred during the first postsurgical year, with less than 20% of patients losing much weight after that. Typically, that weight loss was maintained between years 2 and 3, the investigators said (JAMA 2013 Nov. 4 [doi:10.1001/jama.2013.280928]).

Approximately 67% of patients in the RYGB group had at least partial remission of diabetes at year 3, a percentage similar to that reported in the literature. In contrast, only 27% of those in the LAGB group had at least partial remission of diabetes at year 3, which is a substantially lower rate than the 73% reported in the literature.

At the same time, 0.9% of patients in the RYGB group and 3.2% of those in the LAGB group developed new-onset diabetes during follow-up.

Approximately 62% of the RYGB group had remission of dyslipidemia, while 3.2% developed new-onset dyslipidemia. In contrast, only 27% of the LAGB group had remission of dyslipidemia, while 16% developed new-onset dyslipidemia. The pattern was similar for hyperlipidemia.

Approximately 38% of the RYGB group had remission of hypertension, while 13% developed new-onset hypertension during follow-up. For the LAGB group, the proportion of new-onset cases of hypertension (18.1%) actually exceeded the proportion of remissions (17.4%).

Concerning adverse events, three deaths occurred within 30 days of an RYGB procedure, and two revision procedures and two reversal procedures were required during 3-year follow-up. The corresponding figures for LAGB were zero postsurgical deaths and 77 surgeries to remove the band or revise the surgery during follow-up.

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Courcoulas reported ties to Allergan, Covidien, EndoGastric Solutions, Ethicon J & J Healthcare System, Nutrisystem, and Pfizer, and her associates reported ties to several industry sources.

Clinicians can expect "substantial" weight loss in severely obese patients 3 years after they undergo Roux-en-Y gastric bypass but less impressive weight loss 3 years after laparoscopic adjustable gastric banding, according to a report published online Nov. 4 in JAMA.

In a multicenter follow-up study of 2,348 such patients, those who underwent Roux-en-Y gastric bypass (RYGB) lost a median of 31.5% of their baseline weight and those who underwent laparoscopic adjustable gastric banding (LAGB) lost a median of 15.9% of their baseline weight at 3 years, said Dr. Anita P. Courcoulas of the department of surgery, University of Pittsburgh Medical Center, and her associates.

"Because our patient population was diverse and our results were from a large number of surgeons and surgical centers, long-term sustained weight loss can be expected from RYGB, and the results are likely generalizable. [However,] weight loss associated with the LAGB procedure was less than anticipated ... and less than what would be expected based on published series," the investigators noted.

Dr. Courcoulas and her colleagues in the Longitudinal Assessment of Bariatric Surgery consortium performed this observational cohort study at 10 hospitals across the United States. A total of 1,738 adults underwent RYGB, and 610 underwent LAGB. The median age was 46 years (range, 18-78 years). Most of the study subjects were women (79%), and 14% were nonwhite.

After 3 years, patients in the RYGB group lost a median of 41 kg (range, 110-kg loss to a 1-kg gain). Most of that loss occurred during the first postsurgical year, and typically there was "mild" weight regain between years 2 and 3.

Patients in the LAGB group lost a median of 20 kg (range, 75-kg loss to a 20-kg gain). Most of that loss also occurred during the first postsurgical year, with less than 20% of patients losing much weight after that. Typically, that weight loss was maintained between years 2 and 3, the investigators said (JAMA 2013 Nov. 4 [doi:10.1001/jama.2013.280928]).

Approximately 67% of patients in the RYGB group had at least partial remission of diabetes at year 3, a percentage similar to that reported in the literature. In contrast, only 27% of those in the LAGB group had at least partial remission of diabetes at year 3, which is a substantially lower rate than the 73% reported in the literature.

At the same time, 0.9% of patients in the RYGB group and 3.2% of those in the LAGB group developed new-onset diabetes during follow-up.

Approximately 62% of the RYGB group had remission of dyslipidemia, while 3.2% developed new-onset dyslipidemia. In contrast, only 27% of the LAGB group had remission of dyslipidemia, while 16% developed new-onset dyslipidemia. The pattern was similar for hyperlipidemia.

Approximately 38% of the RYGB group had remission of hypertension, while 13% developed new-onset hypertension during follow-up. For the LAGB group, the proportion of new-onset cases of hypertension (18.1%) actually exceeded the proportion of remissions (17.4%).

Concerning adverse events, three deaths occurred within 30 days of an RYGB procedure, and two revision procedures and two reversal procedures were required during 3-year follow-up. The corresponding figures for LAGB were zero postsurgical deaths and 77 surgeries to remove the band or revise the surgery during follow-up.

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Courcoulas reported ties to Allergan, Covidien, EndoGastric Solutions, Ethicon J & J Healthcare System, Nutrisystem, and Pfizer, and her associates reported ties to several industry sources.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.

Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.

These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.

Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.

For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.

Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).

Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.

Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.

"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.

HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.

This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.

Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.

The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).

At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.

The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.

Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.

At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.

Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.

Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.

Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.

The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.

Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.

Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.

This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.

Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.

The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).

At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.

The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.

Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.

At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.

Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.

Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.

Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.

The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.

Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.

Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.

This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.

Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.

The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).

At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.

The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.

Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.

At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.

Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.

Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.

Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.

The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.

Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.

Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.

This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.

Patients who sustain a concussion need their physicians’ guidance in returning to school in a way that facilitates rather than hinders their recovery, and the American Academy of Pediatrics has issued a clinical report to help.

Most research on pediatric concussions has focused on returning the patient to sports or other physical activities, while data for managing the "return to learn" are sparse. Many published statements emphasize the need for "cognitive rest" – avoiding obvious potential cognitive stressors such as class work and homework – but fall short of identifying and dealing with the myriad other stimuli that can impede recovery or even worsen symptoms, reported Dr. Mark E. Halstead and his associates on the AAP Council on Sports Medicine and Fitness and the AAP Council on School Health (Pediatrics 2013;132:948-57).

©Fuse/Thinkstockphotos.com

An estimated 1.7 million traumatic brain injuries occur each year, many of them concussions. "Given that students typically appear well physically after a concussion, it may be difficult for educators, school administrators, and peers to fully understand the extent of deficits experienced by a student with a concussion." This, in turn, might make school officials reluctant to accept that they must make adjustments for such students.

Pediatricians are in an excellent position to inform these educators, as well as the patients themselves and their families, of the symptoms that might develop and the strategies to prevent or minimize cognitive stress during recovery, said Dr. Halstead, an orthopedic surgeon and sports medicine specialist at Washington University in St. Louis and Children’s Hospital of St. Louis, and his associates. Dr. Halstead also presented the clinical report Oct. 27 at the annual meeting of the American Academy of Pediatrics in Orlando.

The clinical report notes that most concussions resolve within 3 weeks of the injury, so most adjustments to the school environment can be made in the individual classroom setting without the need for a formalized written plan such as a 504 plan or individualized education plan. However, students who require longer-term recovery need more formalized accommodations and modifications.

The report lists typical signs and symptoms of concussion, along with adjustments that teachers and administrators can make to help the child returning to school.

Headache is the most frequent symptom and can recur throughout recovery. School personnel should be made aware that fluorescent lighting, loud noises, and even simply concentrating on a task can elicit headache in these patients, so they should be allowed to take breaks in a quiet area when needed.

Dizziness and lightheadedness also are common and can be provoked by standing quickly, walking in a crowd, or even just viewing motion on a screen or in person. Students with concussion should be allowed to close their eyes or put their heads down on the desk if necessary, and should be permitted to avoid crowded hallways and to move slowly from one place to another.

Common visual symptoms include light sensitivity and blurred or double vision. Students should be allowed to wear a hat with a brim or sunglasses, to turn off or dim room lights, to dim video screens, or to forgo movies or slide presentations. They should be excused if they have trouble reading or writing, or even paying attention to visual tasks.

Sensitivity to noise means that students with concussion might need to be excused from the lunchroom, recess, shop classes, music (band or choir) classes, activities in a gymnasium, and any other excessively noisy location, and should be permitted to use earplugs, Dr. Halstead and his associates said.

Students with concussion also have trouble with concentrating and remembering. Allowances should be made for a student’s difficulty absorbing new material and focusing in the classroom; in particular, testing, especially standardized testing, might need to be postponed until after the student has recovered from the concussion.

Finally, concussions often cause sleep disturbances that can lead to excessive fatigue, tardiness, falling asleep in class, and excessive absences from class. Students might require a late start to the school day or a shortened school day to allow them to rest.

This AAP clinical report was endorsed by the American Medical Society for Sports Medicine, the Brain Injury Association of America, the Canadian Paediatric Society, the National Association of School Nurses, the National Association of School Psychologists, and the National Federation of State High School Associations.

All clinical reports from the AAP expire automatically 5 years after publication unless "reaffirmed, revised, or retired at or before that time."

No conflicts of interest were reported.

Patients who sustain a concussion need their physicians’ guidance in returning to school in a way that facilitates rather than hinders their recovery, and the American Academy of Pediatrics has issued a clinical report to help.

Most research on pediatric concussions has focused on returning the patient to sports or other physical activities, while data for managing the "return to learn" are sparse. Many published statements emphasize the need for "cognitive rest" – avoiding obvious potential cognitive stressors such as class work and homework – but fall short of identifying and dealing with the myriad other stimuli that can impede recovery or even worsen symptoms, reported Dr. Mark E. Halstead and his associates on the AAP Council on Sports Medicine and Fitness and the AAP Council on School Health (Pediatrics 2013;132:948-57).

©Fuse/Thinkstockphotos.com

An estimated 1.7 million traumatic brain injuries occur each year, many of them concussions. "Given that students typically appear well physically after a concussion, it may be difficult for educators, school administrators, and peers to fully understand the extent of deficits experienced by a student with a concussion." This, in turn, might make school officials reluctant to accept that they must make adjustments for such students.

Pediatricians are in an excellent position to inform these educators, as well as the patients themselves and their families, of the symptoms that might develop and the strategies to prevent or minimize cognitive stress during recovery, said Dr. Halstead, an orthopedic surgeon and sports medicine specialist at Washington University in St. Louis and Children’s Hospital of St. Louis, and his associates. Dr. Halstead also presented the clinical report Oct. 27 at the annual meeting of the American Academy of Pediatrics in Orlando.

The clinical report notes that most concussions resolve within 3 weeks of the injury, so most adjustments to the school environment can be made in the individual classroom setting without the need for a formalized written plan such as a 504 plan or individualized education plan. However, students who require longer-term recovery need more formalized accommodations and modifications.

The report lists typical signs and symptoms of concussion, along with adjustments that teachers and administrators can make to help the child returning to school.

Headache is the most frequent symptom and can recur throughout recovery. School personnel should be made aware that fluorescent lighting, loud noises, and even simply concentrating on a task can elicit headache in these patients, so they should be allowed to take breaks in a quiet area when needed.

Dizziness and lightheadedness also are common and can be provoked by standing quickly, walking in a crowd, or even just viewing motion on a screen or in person. Students with concussion should be allowed to close their eyes or put their heads down on the desk if necessary, and should be permitted to avoid crowded hallways and to move slowly from one place to another.

Common visual symptoms include light sensitivity and blurred or double vision. Students should be allowed to wear a hat with a brim or sunglasses, to turn off or dim room lights, to dim video screens, or to forgo movies or slide presentations. They should be excused if they have trouble reading or writing, or even paying attention to visual tasks.

Sensitivity to noise means that students with concussion might need to be excused from the lunchroom, recess, shop classes, music (band or choir) classes, activities in a gymnasium, and any other excessively noisy location, and should be permitted to use earplugs, Dr. Halstead and his associates said.

Students with concussion also have trouble with concentrating and remembering. Allowances should be made for a student’s difficulty absorbing new material and focusing in the classroom; in particular, testing, especially standardized testing, might need to be postponed until after the student has recovered from the concussion.

Finally, concussions often cause sleep disturbances that can lead to excessive fatigue, tardiness, falling asleep in class, and excessive absences from class. Students might require a late start to the school day or a shortened school day to allow them to rest.

This AAP clinical report was endorsed by the American Medical Society for Sports Medicine, the Brain Injury Association of America, the Canadian Paediatric Society, the National Association of School Nurses, the National Association of School Psychologists, and the National Federation of State High School Associations.

All clinical reports from the AAP expire automatically 5 years after publication unless "reaffirmed, revised, or retired at or before that time."

No conflicts of interest were reported.

Patients who sustain a concussion need their physicians’ guidance in returning to school in a way that facilitates rather than hinders their recovery, and the American Academy of Pediatrics has issued a clinical report to help.

Most research on pediatric concussions has focused on returning the patient to sports or other physical activities, while data for managing the "return to learn" are sparse. Many published statements emphasize the need for "cognitive rest" – avoiding obvious potential cognitive stressors such as class work and homework – but fall short of identifying and dealing with the myriad other stimuli that can impede recovery or even worsen symptoms, reported Dr. Mark E. Halstead and his associates on the AAP Council on Sports Medicine and Fitness and the AAP Council on School Health (Pediatrics 2013;132:948-57).

©Fuse/Thinkstockphotos.com

An estimated 1.7 million traumatic brain injuries occur each year, many of them concussions. "Given that students typically appear well physically after a concussion, it may be difficult for educators, school administrators, and peers to fully understand the extent of deficits experienced by a student with a concussion." This, in turn, might make school officials reluctant to accept that they must make adjustments for such students.

Pediatricians are in an excellent position to inform these educators, as well as the patients themselves and their families, of the symptoms that might develop and the strategies to prevent or minimize cognitive stress during recovery, said Dr. Halstead, an orthopedic surgeon and sports medicine specialist at Washington University in St. Louis and Children’s Hospital of St. Louis, and his associates. Dr. Halstead also presented the clinical report Oct. 27 at the annual meeting of the American Academy of Pediatrics in Orlando.

The clinical report notes that most concussions resolve within 3 weeks of the injury, so most adjustments to the school environment can be made in the individual classroom setting without the need for a formalized written plan such as a 504 plan or individualized education plan. However, students who require longer-term recovery need more formalized accommodations and modifications.

The report lists typical signs and symptoms of concussion, along with adjustments that teachers and administrators can make to help the child returning to school.

Headache is the most frequent symptom and can recur throughout recovery. School personnel should be made aware that fluorescent lighting, loud noises, and even simply concentrating on a task can elicit headache in these patients, so they should be allowed to take breaks in a quiet area when needed.

Dizziness and lightheadedness also are common and can be provoked by standing quickly, walking in a crowd, or even just viewing motion on a screen or in person. Students with concussion should be allowed to close their eyes or put their heads down on the desk if necessary, and should be permitted to avoid crowded hallways and to move slowly from one place to another.

Common visual symptoms include light sensitivity and blurred or double vision. Students should be allowed to wear a hat with a brim or sunglasses, to turn off or dim room lights, to dim video screens, or to forgo movies or slide presentations. They should be excused if they have trouble reading or writing, or even paying attention to visual tasks.

Sensitivity to noise means that students with concussion might need to be excused from the lunchroom, recess, shop classes, music (band or choir) classes, activities in a gymnasium, and any other excessively noisy location, and should be permitted to use earplugs, Dr. Halstead and his associates said.

Students with concussion also have trouble with concentrating and remembering. Allowances should be made for a student’s difficulty absorbing new material and focusing in the classroom; in particular, testing, especially standardized testing, might need to be postponed until after the student has recovered from the concussion.

Finally, concussions often cause sleep disturbances that can lead to excessive fatigue, tardiness, falling asleep in class, and excessive absences from class. Students might require a late start to the school day or a shortened school day to allow them to rest.

This AAP clinical report was endorsed by the American Medical Society for Sports Medicine, the Brain Injury Association of America, the Canadian Paediatric Society, the National Association of School Nurses, the National Association of School Psychologists, and the National Federation of State High School Associations.

All clinical reports from the AAP expire automatically 5 years after publication unless "reaffirmed, revised, or retired at or before that time."

No conflicts of interest were reported.

Urologists who incorporate intensity-modulated radiation therapy services into their own practices are much more likely to refer men with newly diagnosed nonmetastatic prostate cancer for IMRT than are other urologists, according to a report. The study was published online Oct. 23 in the New England Journal of Medicine.

Referral to an IMRT service in which the urologist holds a financial stake, also known as self-referral, is controversial because it poses a conflict of interest for the referring physician/investor or physician/owner. Yet many urologists have incorporated IMRT, which enjoys a high reimbursement rate, into their practices: An estimated 19% of urology practices in the United States included IMRT as of 2012, said Jean M. Mitchell, Ph.D., of Georgetown University, Washington.

The increase in IMRT has occurred "despite evidence that all treatments yield similar outcomes" for this type of cancer. "The findings raise concerns regarding the appropriate use of IMRT, especially among older Medicare beneficiaries, for whom the risks of undergoing intensive irradiation probably exceed the benefits," she said.

Dr. Mitchell compared the frequency of IMRT use in two analyses. In the first, she examined claims data for Medicare fee-for-service beneficiaries residing in 26 geographically dispersed states who were newly diagnosed as having nonmetastatic prostate cancer during a 5-year period, when many practices began offering their own IMRT services.

She then identified 35 self-referring urology practices in those states and matched them with an equal number of non–self-referring urology practices in the same area, which served as controls.

Dr. Mitchell found that among beneficiaries treated by self-referring urologists, the rate of IMRT referral increased by over 19%, from 13.1% to 32.3%, during the study period. In contrast, the rate of IMRT referral did not change in patients treated by non–self-referring urologists.

At the same time, the rates of use of two other treatments for noninvasive prostate cancer – brachytherapy and hormone use – fell by a combined 21% in the self-referring practices, she said (N. Engl. J. Med. 2013 Oct. 23 [doi:10.1056/NEJMsa1201141]).

In the second analysis, Dr. Mitchell assessed the records for urologists working at 11 self-referring private practices and urologists employed at 11 non–self-referring cancer centers participating in the National Comprehensive Cancer Network (NCCN) during the same time period. IMRT use by self-referring urologists increased from 9% to 42%, during the course of the study. Another 4.5% of men treated by self-referring urologists also obtained IMRT but attended a different provider to do so.

As in the other study, the corresponding rates of brachytherapy and hormone use in the self-referring practices dropped; in this case by 25%. Active surveillance decreased by 6% and the use of prostatectomy and other procedures declined by 4%.

"By contrast, there was virtually no change in the practice patterns of urologists employed by NCCN centers," where the rate of IMRT use held steady throughout the study period at approximately 8%.

"These findings are consistent with the results of other studies showing substantial increases in the frequency of use of advanced imaging techniques, clinical laboratory testing, and anatomical-pathology services by self-referring physicians," she said.

Financial incentives that may have contributed to the increased use of IMRT are clear. Marketing materials from one company that sells the technology to urologists claim that "treating 1.5 new patients monthly with IMRT could generate more than $425,000 in additional revenue per urologist annually," Dr. Mitchell said.

In some cases, the pressure to simply recoup the costs of investing in IMRT rather than to generate "extra" income may have contributed. Establishing IMRT in a urology practice, which includes hiring advanced support staff, can cost $2 million.

In other cases, "urologists may integrate IMRT into their practice because they believe this treatment will reduce the risk of adverse events and improve quality of life." However, the evidence shows that IMRT is no better than alternative treatments, and that each treatment offers pros and cons that affect quality of life, she added.

This study was funded by the American Society for Radiation Oncology and Georgetown University. Dr. Mitchell reported no financial conflicts of interest.

Urologists who incorporate intensity-modulated radiation therapy services into their own practices are much more likely to refer men with newly diagnosed nonmetastatic prostate cancer for IMRT than are other urologists, according to a report. The study was published online Oct. 23 in the New England Journal of Medicine.

Referral to an IMRT service in which the urologist holds a financial stake, also known as self-referral, is controversial because it poses a conflict of interest for the referring physician/investor or physician/owner. Yet many urologists have incorporated IMRT, which enjoys a high reimbursement rate, into their practices: An estimated 19% of urology practices in the United States included IMRT as of 2012, said Jean M. Mitchell, Ph.D., of Georgetown University, Washington.

The increase in IMRT has occurred "despite evidence that all treatments yield similar outcomes" for this type of cancer. "The findings raise concerns regarding the appropriate use of IMRT, especially among older Medicare beneficiaries, for whom the risks of undergoing intensive irradiation probably exceed the benefits," she said.

Dr. Mitchell compared the frequency of IMRT use in two analyses. In the first, she examined claims data for Medicare fee-for-service beneficiaries residing in 26 geographically dispersed states who were newly diagnosed as having nonmetastatic prostate cancer during a 5-year period, when many practices began offering their own IMRT services.

She then identified 35 self-referring urology practices in those states and matched them with an equal number of non–self-referring urology practices in the same area, which served as controls.

Dr. Mitchell found that among beneficiaries treated by self-referring urologists, the rate of IMRT referral increased by over 19%, from 13.1% to 32.3%, during the study period. In contrast, the rate of IMRT referral did not change in patients treated by non–self-referring urologists.

At the same time, the rates of use of two other treatments for noninvasive prostate cancer – brachytherapy and hormone use – fell by a combined 21% in the self-referring practices, she said (N. Engl. J. Med. 2013 Oct. 23 [doi:10.1056/NEJMsa1201141]).

In the second analysis, Dr. Mitchell assessed the records for urologists working at 11 self-referring private practices and urologists employed at 11 non–self-referring cancer centers participating in the National Comprehensive Cancer Network (NCCN) during the same time period. IMRT use by self-referring urologists increased from 9% to 42%, during the course of the study. Another 4.5% of men treated by self-referring urologists also obtained IMRT but attended a different provider to do so.

As in the other study, the corresponding rates of brachytherapy and hormone use in the self-referring practices dropped; in this case by 25%. Active surveillance decreased by 6% and the use of prostatectomy and other procedures declined by 4%.

"By contrast, there was virtually no change in the practice patterns of urologists employed by NCCN centers," where the rate of IMRT use held steady throughout the study period at approximately 8%.

"These findings are consistent with the results of other studies showing substantial increases in the frequency of use of advanced imaging techniques, clinical laboratory testing, and anatomical-pathology services by self-referring physicians," she said.

Financial incentives that may have contributed to the increased use of IMRT are clear. Marketing materials from one company that sells the technology to urologists claim that "treating 1.5 new patients monthly with IMRT could generate more than $425,000 in additional revenue per urologist annually," Dr. Mitchell said.

In some cases, the pressure to simply recoup the costs of investing in IMRT rather than to generate "extra" income may have contributed. Establishing IMRT in a urology practice, which includes hiring advanced support staff, can cost $2 million.

In other cases, "urologists may integrate IMRT into their practice because they believe this treatment will reduce the risk of adverse events and improve quality of life." However, the evidence shows that IMRT is no better than alternative treatments, and that each treatment offers pros and cons that affect quality of life, she added.

This study was funded by the American Society for Radiation Oncology and Georgetown University. Dr. Mitchell reported no financial conflicts of interest.

Urologists who incorporate intensity-modulated radiation therapy services into their own practices are much more likely to refer men with newly diagnosed nonmetastatic prostate cancer for IMRT than are other urologists, according to a report. The study was published online Oct. 23 in the New England Journal of Medicine.

Referral to an IMRT service in which the urologist holds a financial stake, also known as self-referral, is controversial because it poses a conflict of interest for the referring physician/investor or physician/owner. Yet many urologists have incorporated IMRT, which enjoys a high reimbursement rate, into their practices: An estimated 19% of urology practices in the United States included IMRT as of 2012, said Jean M. Mitchell, Ph.D., of Georgetown University, Washington.

The increase in IMRT has occurred "despite evidence that all treatments yield similar outcomes" for this type of cancer. "The findings raise concerns regarding the appropriate use of IMRT, especially among older Medicare beneficiaries, for whom the risks of undergoing intensive irradiation probably exceed the benefits," she said.

Dr. Mitchell compared the frequency of IMRT use in two analyses. In the first, she examined claims data for Medicare fee-for-service beneficiaries residing in 26 geographically dispersed states who were newly diagnosed as having nonmetastatic prostate cancer during a 5-year period, when many practices began offering their own IMRT services.

She then identified 35 self-referring urology practices in those states and matched them with an equal number of non–self-referring urology practices in the same area, which served as controls.

Dr. Mitchell found that among beneficiaries treated by self-referring urologists, the rate of IMRT referral increased by over 19%, from 13.1% to 32.3%, during the study period. In contrast, the rate of IMRT referral did not change in patients treated by non–self-referring urologists.

At the same time, the rates of use of two other treatments for noninvasive prostate cancer – brachytherapy and hormone use – fell by a combined 21% in the self-referring practices, she said (N. Engl. J. Med. 2013 Oct. 23 [doi:10.1056/NEJMsa1201141]).

In the second analysis, Dr. Mitchell assessed the records for urologists working at 11 self-referring private practices and urologists employed at 11 non–self-referring cancer centers participating in the National Comprehensive Cancer Network (NCCN) during the same time period. IMRT use by self-referring urologists increased from 9% to 42%, during the course of the study. Another 4.5% of men treated by self-referring urologists also obtained IMRT but attended a different provider to do so.

As in the other study, the corresponding rates of brachytherapy and hormone use in the self-referring practices dropped; in this case by 25%. Active surveillance decreased by 6% and the use of prostatectomy and other procedures declined by 4%.

"By contrast, there was virtually no change in the practice patterns of urologists employed by NCCN centers," where the rate of IMRT use held steady throughout the study period at approximately 8%.

"These findings are consistent with the results of other studies showing substantial increases in the frequency of use of advanced imaging techniques, clinical laboratory testing, and anatomical-pathology services by self-referring physicians," she said.

Financial incentives that may have contributed to the increased use of IMRT are clear. Marketing materials from one company that sells the technology to urologists claim that "treating 1.5 new patients monthly with IMRT could generate more than $425,000 in additional revenue per urologist annually," Dr. Mitchell said.

In some cases, the pressure to simply recoup the costs of investing in IMRT rather than to generate "extra" income may have contributed. Establishing IMRT in a urology practice, which includes hiring advanced support staff, can cost $2 million.

In other cases, "urologists may integrate IMRT into their practice because they believe this treatment will reduce the risk of adverse events and improve quality of life." However, the evidence shows that IMRT is no better than alternative treatments, and that each treatment offers pros and cons that affect quality of life, she added.

This study was funded by the American Society for Radiation Oncology and Georgetown University. Dr. Mitchell reported no financial conflicts of interest.

For elderly patients with carotid disease, carotid endarterectomy carries a lower risk of perioperative stroke or transient ischemic attack, the same risk of perioperative MI, and a slightly higher risk of perioperative death compared with carotid stenting, according to a meta-analysis. The results were published online Oct. 23 in JAMA Surgery.

However, the individual elderly patient’s vascular anatomy plays a crucial role in determining perioperative risk, as does his or her overall health and clinical profile.

"The results of [our] analysis suggest that careful consideration of a constellation of clinical and anatomic factors is required before an appropriate treatment of carotid disease in elderly patients is selected. The cardiovascular disease burden and general health of the individual patient should be meticulously evaluated before interventional instead of optimal medical treatment is applied," said Dr. George A. Antoniou of the department of vascular surgery, Hellenic Red Cross Hospital, Athens, and his associates.

Which treatment is the most appropriate for elderly patients with carotid disease is still much debated. Dr. Antoniou and his colleagues performed a comprehensive review of the medical literature since 1986 and a meta-analysis of 44 articles that directly compared outcomes in elderly patients with those of younger patients after carotid endarterectomy (39 studies) or carotid stenting (18 articles).

"Elderly" was defined as older than 80 years in most of these studies, and as older than 75 years in many, but there was great variability among the studies, and some even considered "older than 65 years" to be elderly.

Overall, the meta-analysis included 269,596 endarterectomies in elderly patients against 243,089 in younger patients, and 38,751 carotid stenting procedures in elderly patients against 36,450 in younger patients.

For endarterectomy, the rate of perioperative stroke was not significantly different between elderly (0.9%) and younger (1.2%) patients, nor was the rate of TIA (1.9% vs 1.8%, respectively). However, perioperative mortality was significantly higher in elderly (0.5%) than in younger (0.4%) patients.

In contrast, for carotid stenting, the rate of perioperative stroke was significantly higher for elderly patients (2.4%) than for younger patients (1.7%), as was the rate of TIA (3.6% vs 2.1%). And mortality was not significantly different between elderly patients (0.6%) and younger patients (0.7%), the researchers wrote (JAMA Surg. 2013 Oct. 23 [doi:10.1001/jamasurg.2013.4135]).

Both procedures were associated with an increased rate of perioperative MI in elderly patients, compared with younger patients. These rates were 2.2% in elderly patients, compared with 1.4% in younger patients undergoing endarterectomy; and 2.3% in elderly patients, compared with 1.5% in younger patients undergoing carotid stenting.

These findings remained robust in sensitivity analyses.

"It seems that endarterectomy is associated with improved neurologic outcomes compared with carotid stenting in elderly patients, at the expense of increased perioperative mortality." However, the small increase in mortality seen with endarterectomy – one-tenth of 1% – may not be clinically significant, Dr. Antoniou and his associates said.

Moreover, neurologic risk is closely tied to vascular anatomy. Elderly patients tend to have more unfavorable anatomy than do younger patients, but should be assessed on an individual basis. Unfavorable traits include heavily calcified and tortuous supra-aortic branches, as well as adverse morphology of the aortic arch such as elongation, distortion, and stenosis.

Manipulating the stenting instruments through such features may in itself raise the risk of neurologic sequelae. It also makes the procedure more technically difficult, which increases the risk of endothelial trauma, thrombus dislodgement, and thromboembolic events.

"In addition, elderly patients with significant extracranial atherosclerotic disease are likely to have a compromised cerebrovascular reserve, which makes them more susceptible to ischemic events from cerebral microembolization," the researchers said.

No financial conflicts of interest were disclosed.

For elderly patients with carotid disease, carotid endarterectomy carries a lower risk of perioperative stroke or transient ischemic attack, the same risk of perioperative MI, and a slightly higher risk of perioperative death compared with carotid stenting, according to a meta-analysis. The results were published online Oct. 23 in JAMA Surgery.

However, the individual elderly patient’s vascular anatomy plays a crucial role in determining perioperative risk, as does his or her overall health and clinical profile.

"The results of [our] analysis suggest that careful consideration of a constellation of clinical and anatomic factors is required before an appropriate treatment of carotid disease in elderly patients is selected. The cardiovascular disease burden and general health of the individual patient should be meticulously evaluated before interventional instead of optimal medical treatment is applied," said Dr. George A. Antoniou of the department of vascular surgery, Hellenic Red Cross Hospital, Athens, and his associates.

Which treatment is the most appropriate for elderly patients with carotid disease is still much debated. Dr. Antoniou and his colleagues performed a comprehensive review of the medical literature since 1986 and a meta-analysis of 44 articles that directly compared outcomes in elderly patients with those of younger patients after carotid endarterectomy (39 studies) or carotid stenting (18 articles).

"Elderly" was defined as older than 80 years in most of these studies, and as older than 75 years in many, but there was great variability among the studies, and some even considered "older than 65 years" to be elderly.

Overall, the meta-analysis included 269,596 endarterectomies in elderly patients against 243,089 in younger patients, and 38,751 carotid stenting procedures in elderly patients against 36,450 in younger patients.

For endarterectomy, the rate of perioperative stroke was not significantly different between elderly (0.9%) and younger (1.2%) patients, nor was the rate of TIA (1.9% vs 1.8%, respectively). However, perioperative mortality was significantly higher in elderly (0.5%) than in younger (0.4%) patients.

In contrast, for carotid stenting, the rate of perioperative stroke was significantly higher for elderly patients (2.4%) than for younger patients (1.7%), as was the rate of TIA (3.6% vs 2.1%). And mortality was not significantly different between elderly patients (0.6%) and younger patients (0.7%), the researchers wrote (JAMA Surg. 2013 Oct. 23 [doi:10.1001/jamasurg.2013.4135]).

Both procedures were associated with an increased rate of perioperative MI in elderly patients, compared with younger patients. These rates were 2.2% in elderly patients, compared with 1.4% in younger patients undergoing endarterectomy; and 2.3% in elderly patients, compared with 1.5% in younger patients undergoing carotid stenting.

These findings remained robust in sensitivity analyses.

"It seems that endarterectomy is associated with improved neurologic outcomes compared with carotid stenting in elderly patients, at the expense of increased perioperative mortality." However, the small increase in mortality seen with endarterectomy – one-tenth of 1% – may not be clinically significant, Dr. Antoniou and his associates said.

Moreover, neurologic risk is closely tied to vascular anatomy. Elderly patients tend to have more unfavorable anatomy than do younger patients, but should be assessed on an individual basis. Unfavorable traits include heavily calcified and tortuous supra-aortic branches, as well as adverse morphology of the aortic arch such as elongation, distortion, and stenosis.

Manipulating the stenting instruments through such features may in itself raise the risk of neurologic sequelae. It also makes the procedure more technically difficult, which increases the risk of endothelial trauma, thrombus dislodgement, and thromboembolic events.

"In addition, elderly patients with significant extracranial atherosclerotic disease are likely to have a compromised cerebrovascular reserve, which makes them more susceptible to ischemic events from cerebral microembolization," the researchers said.

No financial conflicts of interest were disclosed.

For elderly patients with carotid disease, carotid endarterectomy carries a lower risk of perioperative stroke or transient ischemic attack, the same risk of perioperative MI, and a slightly higher risk of perioperative death compared with carotid stenting, according to a meta-analysis. The results were published online Oct. 23 in JAMA Surgery.

However, the individual elderly patient’s vascular anatomy plays a crucial role in determining perioperative risk, as does his or her overall health and clinical profile.

"The results of [our] analysis suggest that careful consideration of a constellation of clinical and anatomic factors is required before an appropriate treatment of carotid disease in elderly patients is selected. The cardiovascular disease burden and general health of the individual patient should be meticulously evaluated before interventional instead of optimal medical treatment is applied," said Dr. George A. Antoniou of the department of vascular surgery, Hellenic Red Cross Hospital, Athens, and his associates.

Which treatment is the most appropriate for elderly patients with carotid disease is still much debated. Dr. Antoniou and his colleagues performed a comprehensive review of the medical literature since 1986 and a meta-analysis of 44 articles that directly compared outcomes in elderly patients with those of younger patients after carotid endarterectomy (39 studies) or carotid stenting (18 articles).

"Elderly" was defined as older than 80 years in most of these studies, and as older than 75 years in many, but there was great variability among the studies, and some even considered "older than 65 years" to be elderly.

Overall, the meta-analysis included 269,596 endarterectomies in elderly patients against 243,089 in younger patients, and 38,751 carotid stenting procedures in elderly patients against 36,450 in younger patients.

For endarterectomy, the rate of perioperative stroke was not significantly different between elderly (0.9%) and younger (1.2%) patients, nor was the rate of TIA (1.9% vs 1.8%, respectively). However, perioperative mortality was significantly higher in elderly (0.5%) than in younger (0.4%) patients.

In contrast, for carotid stenting, the rate of perioperative stroke was significantly higher for elderly patients (2.4%) than for younger patients (1.7%), as was the rate of TIA (3.6% vs 2.1%). And mortality was not significantly different between elderly patients (0.6%) and younger patients (0.7%), the researchers wrote (JAMA Surg. 2013 Oct. 23 [doi:10.1001/jamasurg.2013.4135]).

Both procedures were associated with an increased rate of perioperative MI in elderly patients, compared with younger patients. These rates were 2.2% in elderly patients, compared with 1.4% in younger patients undergoing endarterectomy; and 2.3% in elderly patients, compared with 1.5% in younger patients undergoing carotid stenting.

These findings remained robust in sensitivity analyses.

"It seems that endarterectomy is associated with improved neurologic outcomes compared with carotid stenting in elderly patients, at the expense of increased perioperative mortality." However, the small increase in mortality seen with endarterectomy – one-tenth of 1% – may not be clinically significant, Dr. Antoniou and his associates said.

Moreover, neurologic risk is closely tied to vascular anatomy. Elderly patients tend to have more unfavorable anatomy than do younger patients, but should be assessed on an individual basis. Unfavorable traits include heavily calcified and tortuous supra-aortic branches, as well as adverse morphology of the aortic arch such as elongation, distortion, and stenosis.

Manipulating the stenting instruments through such features may in itself raise the risk of neurologic sequelae. It also makes the procedure more technically difficult, which increases the risk of endothelial trauma, thrombus dislodgement, and thromboembolic events.

"In addition, elderly patients with significant extracranial atherosclerotic disease are likely to have a compromised cerebrovascular reserve, which makes them more susceptible to ischemic events from cerebral microembolization," the researchers said.

No financial conflicts of interest were disclosed.