Mary Ann Moon

Major Finding: 81% of dermatologists, 56% of internists, and 60% of family physicians report that they routinely perform full-body examinations for skin cancer.

Data Source: Survey of a representative sample of 679 dermatologists, 431 internists, and 559 family physicians.

Disclosures: The National Cancer Institute supported the study. No financial conflicts of interest were reported.

A majority of dermatologists, internists, and family physicians routinely perform full-body examinations for skin cancer – but time constraints and patient reluctance are common barriers to better exam rates, according to a recent report.

A total of 81% of dermatologists, 56% of internists, and 60% of family physicians in a nationally representative sample reported that they routinely perform skin cancer examinations.

All three groups of physicians also identified barriers to performing skin examinations more often, but the barriers varied by specialty, said Susan A. Oliveria, Sc.D., of Memorial Sloan-Kettering Cancer Center's dermatology service, New York, and her associates (Arch. Dermatol. 2011;147:39-44).

The investigators assessed skin cancer screening practices because little is known about the subject, and a better understanding both of the obstacles and of the facilitating factors could help improve primary and secondary screening.

To examine the issue, the researchers used data from a survey to which 1,669 physicians in group or solo private practice responded. The respondents included 679 dermatologists, 431 internists, and 559 family physicians. Most reported that they saw 200-600 patients per month, and most were aged 41-60 years.

Approximately 54% of internists and family physicians reported that time constraints prevented them from doing full-body skin exams more frequently, compared with 31% of dermatologists. Half of the internists and family physicians also said that “competing comorbidities” often took priority over skin exams, compared with only 16% of dermatologists.

In contrast, significantly more dermatologists (44%) identified patient embarrassment or reluctance as a barrier to performing full-body skin exams, compared with internists (33%) or family physicians (31%). That is likely because most patients see a dermatologist for an isolated skin condition such as a wart or rash, the investigators noted, and do not expect to undress for a full-body exam.

In contrast, patients expect to undress for an internist or family physician, because disrobing for pelvic or rectal exams often is part of their annual physical examinations. Moreover, primary care physicians “have years to build up relationships with their patients,” the study authors explained, while dermatologists typically do not.

To overcome that barrier, “dermatologists could educate their patients … by providing them with written material to read and establishing a comforting physician-patient relationship,” Dr. Oliveria and her colleagues said.

All the physicians said that they were more likely to screen for skin cancer in patients who had one or more risk factors, but only 87% of dermatologists, 65% of internists, and 70% of family physicians reported that they performed full-body exams in most high-risk patients.

Another common reason for performing a full-body skin cancer screen was the same for all three specialties: having a patient ask to have such an exam or to have a suspicious mole checked. That shows that it is important to maintain public education programs encouraging patients to request such exams, the researchers said.

Fewer internists (56%) and family physicians (54%) than dermatologists (78%) reported that their skill and expertise at performing skin exams and diagnosing skin cancer facilitated their screening practices. That finding suggests that enhanced dermatologic training in medical school and continuing medical education programs would be beneficial, they added.

Major Finding: 81% of dermatologists, 56% of internists, and 60% of family physicians report that they routinely perform full-body examinations for skin cancer.

Data Source: Survey of a representative sample of 679 dermatologists, 431 internists, and 559 family physicians.

Disclosures: The National Cancer Institute supported the study. No financial conflicts of interest were reported.

A majority of dermatologists, internists, and family physicians routinely perform full-body examinations for skin cancer – but time constraints and patient reluctance are common barriers to better exam rates, according to a recent report.

A total of 81% of dermatologists, 56% of internists, and 60% of family physicians in a nationally representative sample reported that they routinely perform skin cancer examinations.

All three groups of physicians also identified barriers to performing skin examinations more often, but the barriers varied by specialty, said Susan A. Oliveria, Sc.D., of Memorial Sloan-Kettering Cancer Center's dermatology service, New York, and her associates (Arch. Dermatol. 2011;147:39-44).

The investigators assessed skin cancer screening practices because little is known about the subject, and a better understanding both of the obstacles and of the facilitating factors could help improve primary and secondary screening.

To examine the issue, the researchers used data from a survey to which 1,669 physicians in group or solo private practice responded. The respondents included 679 dermatologists, 431 internists, and 559 family physicians. Most reported that they saw 200-600 patients per month, and most were aged 41-60 years.

Approximately 54% of internists and family physicians reported that time constraints prevented them from doing full-body skin exams more frequently, compared with 31% of dermatologists. Half of the internists and family physicians also said that “competing comorbidities” often took priority over skin exams, compared with only 16% of dermatologists.

In contrast, significantly more dermatologists (44%) identified patient embarrassment or reluctance as a barrier to performing full-body skin exams, compared with internists (33%) or family physicians (31%). That is likely because most patients see a dermatologist for an isolated skin condition such as a wart or rash, the investigators noted, and do not expect to undress for a full-body exam.

In contrast, patients expect to undress for an internist or family physician, because disrobing for pelvic or rectal exams often is part of their annual physical examinations. Moreover, primary care physicians “have years to build up relationships with their patients,” the study authors explained, while dermatologists typically do not.

To overcome that barrier, “dermatologists could educate their patients … by providing them with written material to read and establishing a comforting physician-patient relationship,” Dr. Oliveria and her colleagues said.

All the physicians said that they were more likely to screen for skin cancer in patients who had one or more risk factors, but only 87% of dermatologists, 65% of internists, and 70% of family physicians reported that they performed full-body exams in most high-risk patients.

Another common reason for performing a full-body skin cancer screen was the same for all three specialties: having a patient ask to have such an exam or to have a suspicious mole checked. That shows that it is important to maintain public education programs encouraging patients to request such exams, the researchers said.

Fewer internists (56%) and family physicians (54%) than dermatologists (78%) reported that their skill and expertise at performing skin exams and diagnosing skin cancer facilitated their screening practices. That finding suggests that enhanced dermatologic training in medical school and continuing medical education programs would be beneficial, they added.

Major Finding: 81% of dermatologists, 56% of internists, and 60% of family physicians report that they routinely perform full-body examinations for skin cancer.

Data Source: Survey of a representative sample of 679 dermatologists, 431 internists, and 559 family physicians.

Disclosures: The National Cancer Institute supported the study. No financial conflicts of interest were reported.

A majority of dermatologists, internists, and family physicians routinely perform full-body examinations for skin cancer – but time constraints and patient reluctance are common barriers to better exam rates, according to a recent report.

A total of 81% of dermatologists, 56% of internists, and 60% of family physicians in a nationally representative sample reported that they routinely perform skin cancer examinations.

All three groups of physicians also identified barriers to performing skin examinations more often, but the barriers varied by specialty, said Susan A. Oliveria, Sc.D., of Memorial Sloan-Kettering Cancer Center's dermatology service, New York, and her associates (Arch. Dermatol. 2011;147:39-44).

The investigators assessed skin cancer screening practices because little is known about the subject, and a better understanding both of the obstacles and of the facilitating factors could help improve primary and secondary screening.

To examine the issue, the researchers used data from a survey to which 1,669 physicians in group or solo private practice responded. The respondents included 679 dermatologists, 431 internists, and 559 family physicians. Most reported that they saw 200-600 patients per month, and most were aged 41-60 years.

Approximately 54% of internists and family physicians reported that time constraints prevented them from doing full-body skin exams more frequently, compared with 31% of dermatologists. Half of the internists and family physicians also said that “competing comorbidities” often took priority over skin exams, compared with only 16% of dermatologists.

In contrast, significantly more dermatologists (44%) identified patient embarrassment or reluctance as a barrier to performing full-body skin exams, compared with internists (33%) or family physicians (31%). That is likely because most patients see a dermatologist for an isolated skin condition such as a wart or rash, the investigators noted, and do not expect to undress for a full-body exam.

In contrast, patients expect to undress for an internist or family physician, because disrobing for pelvic or rectal exams often is part of their annual physical examinations. Moreover, primary care physicians “have years to build up relationships with their patients,” the study authors explained, while dermatologists typically do not.

To overcome that barrier, “dermatologists could educate their patients … by providing them with written material to read and establishing a comforting physician-patient relationship,” Dr. Oliveria and her colleagues said.

All the physicians said that they were more likely to screen for skin cancer in patients who had one or more risk factors, but only 87% of dermatologists, 65% of internists, and 70% of family physicians reported that they performed full-body exams in most high-risk patients.

Another common reason for performing a full-body skin cancer screen was the same for all three specialties: having a patient ask to have such an exam or to have a suspicious mole checked. That shows that it is important to maintain public education programs encouraging patients to request such exams, the researchers said.

Fewer internists (56%) and family physicians (54%) than dermatologists (78%) reported that their skill and expertise at performing skin exams and diagnosing skin cancer facilitated their screening practices. That finding suggests that enhanced dermatologic training in medical school and continuing medical education programs would be beneficial, they added.

Major Finding: The risks of opioid use in elderly patients vary substantially according to the specific drug used and the duration of use.

Data Source: A propensity-matched cohort analysis involving more than 31,000 Medicare patients.

Disclosures: This study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee and an unpaid member of the data safety monitoring board for an analgesic trial, both sponsored by Pfizer.

The risks of opioid use for elderly patients with nonmalignant pain vary considerably by different agents and by different durations of use, a study has shown.

Patients taking codeine for more than 180 days are at increased risk for cardiovascular events, and those taking oxycodone or codeine for only 30 days are at increased risk for mortality due to any cause, said Dr. Daniel H. Solomon and his associates in the rheumatology department and the pharmacoepidemiology division at Brigham and Women's Hospital, Boston.

“This study's findings do not agree with a commonly held belief that all opioids are associated with similar risk,” the investigators noted.

They compared the safety profiles of different opioids for the treatment of nonmalignant pain in elderly patients because “relatively little attention has been paid” to this issue even though the use of these drugs has increased by 50%-100% in recent years. In contrast, patients and physicians are relatively well informed about the toxicities of NSAIDs used for the same indications.

Dr. Solomon and his colleagues analyzed information in two states' Medicare databases of pharmaceutical coverage for low-income patients (mean age, 79 years) between 1995 and 2005. They were able to match 6,275 subjects who took five of the most commonly prescribed opioids for a variety of baseline factors using propensity scores.

Hydrocodone was used as the reference exposure, to which codeine, oxycodone, propoxyphene, and tramadol were compared.

The risk of cardiovascular events including MI, stroke, heart failure, revascularization, and cardiac death was similar across the five opioid groups after 30 days of use, but by 180 days the risk with codeine was significantly elevated (risk ratio, 1.62), compared with the other four opioids.

This finding is surprising and requires validation in other study populations, the investigators said (Arch. Intern. Med. 2010;170:1979-86).

All-cause mortality was elevated after only 30 days of use for patients taking oxycodone (RR, 2.43) or codeine (RR, 2.05), but not for those taking other opioids.

In contrast, the risk of fracture of the hip, pelvis, wrist, or humerus was significantly reduced after 30 days of treatment for patients taking tramadol (RR, 0.21) or propoxyphene (RR, 0.54)

The risk of gastrointestinal adverse events – which included upper or lower GI bleeding and bowel obstruction – did not differ across opioid groups at either 30 days or 180 days.

These risks remained consistent through a range of sensitivity analyses of the data. Importantly, the risks also were consistent regardless of whether patients were taking low, medium, high, or very high doses of the drugs. “The risks were substantial and translated into numbers needed to treat that would be considered clinically significant,” Dr. Solomon and his associates wrote.

View on the News

Opioids Not 'Interchangeable'

These findings “challenge the conventional notion that the safety profiles of opioids are generally interchangeable” and carry two important implications, said Dr. William C. Becker and Dr. Patrick G. O'Connor.

The first and most crucial implication is that the frequent use of codeine must be reexamined. “The untested but widespread assumption that codeine is safer from an addiction standpoint because of its lower potency may need to give way to these data demonstrating increased risk of cardiovascular events and all-cause mortality. If codeine is of middling efficacy for pain and is more risky than other opioids, there would be little reason to use it,” they noted.

Second, the elevated fracture risk with opioid use “has solid biological plausibility” by two mechanisms of action: Opioids raise the rate of falls, and they suppress the production of androgen and estradiol, imperiling bone health. “Efforts to improve patients' understanding of safe medication-taking practices, providers' understanding of safe prescribing practices, and standardization of safety-oriented follow-up are sorely needed,” they said.

DR. BECKER and DR. O'CONNOR are with Yale University, New Haven, Conn. They reported no relevant financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

Major Finding: The risks of opioid use in elderly patients vary substantially according to the specific drug used and the duration of use.

Data Source: A propensity-matched cohort analysis involving more than 31,000 Medicare patients.

Disclosures: This study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee and an unpaid member of the data safety monitoring board for an analgesic trial, both sponsored by Pfizer.

The risks of opioid use for elderly patients with nonmalignant pain vary considerably by different agents and by different durations of use, a study has shown.

Patients taking codeine for more than 180 days are at increased risk for cardiovascular events, and those taking oxycodone or codeine for only 30 days are at increased risk for mortality due to any cause, said Dr. Daniel H. Solomon and his associates in the rheumatology department and the pharmacoepidemiology division at Brigham and Women's Hospital, Boston.

“This study's findings do not agree with a commonly held belief that all opioids are associated with similar risk,” the investigators noted.

They compared the safety profiles of different opioids for the treatment of nonmalignant pain in elderly patients because “relatively little attention has been paid” to this issue even though the use of these drugs has increased by 50%-100% in recent years. In contrast, patients and physicians are relatively well informed about the toxicities of NSAIDs used for the same indications.

Dr. Solomon and his colleagues analyzed information in two states' Medicare databases of pharmaceutical coverage for low-income patients (mean age, 79 years) between 1995 and 2005. They were able to match 6,275 subjects who took five of the most commonly prescribed opioids for a variety of baseline factors using propensity scores.

Hydrocodone was used as the reference exposure, to which codeine, oxycodone, propoxyphene, and tramadol were compared.

The risk of cardiovascular events including MI, stroke, heart failure, revascularization, and cardiac death was similar across the five opioid groups after 30 days of use, but by 180 days the risk with codeine was significantly elevated (risk ratio, 1.62), compared with the other four opioids.

This finding is surprising and requires validation in other study populations, the investigators said (Arch. Intern. Med. 2010;170:1979-86).

All-cause mortality was elevated after only 30 days of use for patients taking oxycodone (RR, 2.43) or codeine (RR, 2.05), but not for those taking other opioids.

In contrast, the risk of fracture of the hip, pelvis, wrist, or humerus was significantly reduced after 30 days of treatment for patients taking tramadol (RR, 0.21) or propoxyphene (RR, 0.54)

The risk of gastrointestinal adverse events – which included upper or lower GI bleeding and bowel obstruction – did not differ across opioid groups at either 30 days or 180 days.

These risks remained consistent through a range of sensitivity analyses of the data. Importantly, the risks also were consistent regardless of whether patients were taking low, medium, high, or very high doses of the drugs. “The risks were substantial and translated into numbers needed to treat that would be considered clinically significant,” Dr. Solomon and his associates wrote.

View on the News

Opioids Not 'Interchangeable'

These findings “challenge the conventional notion that the safety profiles of opioids are generally interchangeable” and carry two important implications, said Dr. William C. Becker and Dr. Patrick G. O'Connor.

The first and most crucial implication is that the frequent use of codeine must be reexamined. “The untested but widespread assumption that codeine is safer from an addiction standpoint because of its lower potency may need to give way to these data demonstrating increased risk of cardiovascular events and all-cause mortality. If codeine is of middling efficacy for pain and is more risky than other opioids, there would be little reason to use it,” they noted.

Second, the elevated fracture risk with opioid use “has solid biological plausibility” by two mechanisms of action: Opioids raise the rate of falls, and they suppress the production of androgen and estradiol, imperiling bone health. “Efforts to improve patients' understanding of safe medication-taking practices, providers' understanding of safe prescribing practices, and standardization of safety-oriented follow-up are sorely needed,” they said.

DR. BECKER and DR. O'CONNOR are with Yale University, New Haven, Conn. They reported no relevant financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

Major Finding: The risks of opioid use in elderly patients vary substantially according to the specific drug used and the duration of use.

Data Source: A propensity-matched cohort analysis involving more than 31,000 Medicare patients.

Disclosures: This study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee and an unpaid member of the data safety monitoring board for an analgesic trial, both sponsored by Pfizer.

The risks of opioid use for elderly patients with nonmalignant pain vary considerably by different agents and by different durations of use, a study has shown.

Patients taking codeine for more than 180 days are at increased risk for cardiovascular events, and those taking oxycodone or codeine for only 30 days are at increased risk for mortality due to any cause, said Dr. Daniel H. Solomon and his associates in the rheumatology department and the pharmacoepidemiology division at Brigham and Women's Hospital, Boston.

“This study's findings do not agree with a commonly held belief that all opioids are associated with similar risk,” the investigators noted.

They compared the safety profiles of different opioids for the treatment of nonmalignant pain in elderly patients because “relatively little attention has been paid” to this issue even though the use of these drugs has increased by 50%-100% in recent years. In contrast, patients and physicians are relatively well informed about the toxicities of NSAIDs used for the same indications.

Dr. Solomon and his colleagues analyzed information in two states' Medicare databases of pharmaceutical coverage for low-income patients (mean age, 79 years) between 1995 and 2005. They were able to match 6,275 subjects who took five of the most commonly prescribed opioids for a variety of baseline factors using propensity scores.

Hydrocodone was used as the reference exposure, to which codeine, oxycodone, propoxyphene, and tramadol were compared.

The risk of cardiovascular events including MI, stroke, heart failure, revascularization, and cardiac death was similar across the five opioid groups after 30 days of use, but by 180 days the risk with codeine was significantly elevated (risk ratio, 1.62), compared with the other four opioids.

This finding is surprising and requires validation in other study populations, the investigators said (Arch. Intern. Med. 2010;170:1979-86).

All-cause mortality was elevated after only 30 days of use for patients taking oxycodone (RR, 2.43) or codeine (RR, 2.05), but not for those taking other opioids.

In contrast, the risk of fracture of the hip, pelvis, wrist, or humerus was significantly reduced after 30 days of treatment for patients taking tramadol (RR, 0.21) or propoxyphene (RR, 0.54)

The risk of gastrointestinal adverse events – which included upper or lower GI bleeding and bowel obstruction – did not differ across opioid groups at either 30 days or 180 days.

These risks remained consistent through a range of sensitivity analyses of the data. Importantly, the risks also were consistent regardless of whether patients were taking low, medium, high, or very high doses of the drugs. “The risks were substantial and translated into numbers needed to treat that would be considered clinically significant,” Dr. Solomon and his associates wrote.

View on the News

Opioids Not 'Interchangeable'

These findings “challenge the conventional notion that the safety profiles of opioids are generally interchangeable” and carry two important implications, said Dr. William C. Becker and Dr. Patrick G. O'Connor.

The first and most crucial implication is that the frequent use of codeine must be reexamined. “The untested but widespread assumption that codeine is safer from an addiction standpoint because of its lower potency may need to give way to these data demonstrating increased risk of cardiovascular events and all-cause mortality. If codeine is of middling efficacy for pain and is more risky than other opioids, there would be little reason to use it,” they noted.

Second, the elevated fracture risk with opioid use “has solid biological plausibility” by two mechanisms of action: Opioids raise the rate of falls, and they suppress the production of androgen and estradiol, imperiling bone health. “Efforts to improve patients' understanding of safe medication-taking practices, providers' understanding of safe prescribing practices, and standardization of safety-oriented follow-up are sorely needed,” they said.

DR. BECKER and DR. O'CONNOR are with Yale University, New Haven, Conn. They reported no relevant financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

HDL cholesterol's efflux capacity, a measure of its ability to promote cholesterol efflux from lipid-laden macrophages, was strongly inversely correlated with atherosclerotic burden in a study of two independent groups of subjects.

In a study assessing HDL cholesterol efflux capacity in two independent populations, this key measure of HDL function was a stronger predictor of both subclinical atherosclerosis disease (as assessed by carotid intima-media thickness) and coronary artery disease than was HDL level itself.

“These results could be important in the assessment of new therapies targeting HDL metabolism and reverse cholesterol transport,” and may even guide the development of new treatments, said Dr. Amit V. Khera of the cardiovascular institute at the University of Pennsylvania, Philadelphia, and his associates.

They first tested efflux capacity in serum samples from a cohort of 203 healthy white adults participating in a study of HDL-related biomarkers and atherosclerosis. These subjects underwent measurement of carotid artery intima-media thickness as part of that study.

There was no association between HDL level and subclinical CAD. In contrast, there was a significant inverse correlation between HDL cholesterol efflux capacity and subclinical CAD, which remained robust after the data were adjusted for HDL and apolipoprotein A-1 levels.

The investigators then assessed efflux capacity using serum samples from 793 white participants in a case-control cohort who underwent cardiac catheterization. The 442 patients found to have CAD showed significantly lower efflux capacity than did the 351 control subjects who were free of CAD.

In a further analysis, the proportion of patients with CAD decreased consistently with increasing efflux capacity. When the cohort was divided into quartiles of efflux capacity, the quartile with the highest efflux capacity showed a distinct decrease in CAD compared with the quartile with the lowest capacity.

All of these correlations remained robust after adjustment for subject age, sex, and traditional cardiovascular disease risk factors, Dr. Khera and his colleagues said (N. Engl. J. Med. 2010;364:127-35).

“Although cholesterol efflux from macrophages represents only a small fraction of overall flux through the reverse-cholesterol-transport pathway, it is probably the component that is most relevant to atheroprotection,” they noted.

“These findings reinforce the concept that assessment of HDL function” – not just HDL levels – “may prove informative in refining our understanding of HDL-mediated atheroprotection,” the researchers added.

This study was supported by the National Heart, Lung, and Blood Institute; the National Center for Research Resources; the Doris Duke Charitable Foundation; and the Howard Hughes Medical Institute. Dr. Khera's associates reported ties to Kinemed, Vascular Strategies, and GlaxoSmithKline, as well as involvement with a patent on cell culture systems for determining cholesterol efflux potential in serum.

View on the News

HDL Function Deserves Further Study

The central hypothesis of the study, which was based on findings from studies in animals and cell cultures, was that HDL promotes cholesterol efflux from macrophage foam cells in atheromatous vessels, thus decreasing both the cholesterol burden and macrophage-driven inflammation, said Dr. Jay Heinecke.

The results thus “provide important evidence that the ability of HDL to promote cholesterol efflux from macrophage foam cells is a key property that explains in part the inverse relationship between HDL and the risk of atherosclerotic coronary artery disease in humans.”

Measuring efflux capacity thus may become a useful tool in further investigation of HDL function as well as in developing treatments for CAD, he said.

DR. HEINECKE is with the University of Washington, Seattle. He reported ties to several drug and biomedical technology companies. These comments are taken from his editorial accompanying Dr. Khera's report (N. Engl. J. Med. 2010;364:170-1).

HDL cholesterol's efflux capacity, a measure of its ability to promote cholesterol efflux from lipid-laden macrophages, was strongly inversely correlated with atherosclerotic burden in a study of two independent groups of subjects.

In a study assessing HDL cholesterol efflux capacity in two independent populations, this key measure of HDL function was a stronger predictor of both subclinical atherosclerosis disease (as assessed by carotid intima-media thickness) and coronary artery disease than was HDL level itself.

“These results could be important in the assessment of new therapies targeting HDL metabolism and reverse cholesterol transport,” and may even guide the development of new treatments, said Dr. Amit V. Khera of the cardiovascular institute at the University of Pennsylvania, Philadelphia, and his associates.

They first tested efflux capacity in serum samples from a cohort of 203 healthy white adults participating in a study of HDL-related biomarkers and atherosclerosis. These subjects underwent measurement of carotid artery intima-media thickness as part of that study.

There was no association between HDL level and subclinical CAD. In contrast, there was a significant inverse correlation between HDL cholesterol efflux capacity and subclinical CAD, which remained robust after the data were adjusted for HDL and apolipoprotein A-1 levels.

The investigators then assessed efflux capacity using serum samples from 793 white participants in a case-control cohort who underwent cardiac catheterization. The 442 patients found to have CAD showed significantly lower efflux capacity than did the 351 control subjects who were free of CAD.

In a further analysis, the proportion of patients with CAD decreased consistently with increasing efflux capacity. When the cohort was divided into quartiles of efflux capacity, the quartile with the highest efflux capacity showed a distinct decrease in CAD compared with the quartile with the lowest capacity.

All of these correlations remained robust after adjustment for subject age, sex, and traditional cardiovascular disease risk factors, Dr. Khera and his colleagues said (N. Engl. J. Med. 2010;364:127-35).

“Although cholesterol efflux from macrophages represents only a small fraction of overall flux through the reverse-cholesterol-transport pathway, it is probably the component that is most relevant to atheroprotection,” they noted.

“These findings reinforce the concept that assessment of HDL function” – not just HDL levels – “may prove informative in refining our understanding of HDL-mediated atheroprotection,” the researchers added.

This study was supported by the National Heart, Lung, and Blood Institute; the National Center for Research Resources; the Doris Duke Charitable Foundation; and the Howard Hughes Medical Institute. Dr. Khera's associates reported ties to Kinemed, Vascular Strategies, and GlaxoSmithKline, as well as involvement with a patent on cell culture systems for determining cholesterol efflux potential in serum.

View on the News

HDL Function Deserves Further Study

The central hypothesis of the study, which was based on findings from studies in animals and cell cultures, was that HDL promotes cholesterol efflux from macrophage foam cells in atheromatous vessels, thus decreasing both the cholesterol burden and macrophage-driven inflammation, said Dr. Jay Heinecke.

The results thus “provide important evidence that the ability of HDL to promote cholesterol efflux from macrophage foam cells is a key property that explains in part the inverse relationship between HDL and the risk of atherosclerotic coronary artery disease in humans.”

Measuring efflux capacity thus may become a useful tool in further investigation of HDL function as well as in developing treatments for CAD, he said.

DR. HEINECKE is with the University of Washington, Seattle. He reported ties to several drug and biomedical technology companies. These comments are taken from his editorial accompanying Dr. Khera's report (N. Engl. J. Med. 2010;364:170-1).

HDL cholesterol's efflux capacity, a measure of its ability to promote cholesterol efflux from lipid-laden macrophages, was strongly inversely correlated with atherosclerotic burden in a study of two independent groups of subjects.

In a study assessing HDL cholesterol efflux capacity in two independent populations, this key measure of HDL function was a stronger predictor of both subclinical atherosclerosis disease (as assessed by carotid intima-media thickness) and coronary artery disease than was HDL level itself.

“These results could be important in the assessment of new therapies targeting HDL metabolism and reverse cholesterol transport,” and may even guide the development of new treatments, said Dr. Amit V. Khera of the cardiovascular institute at the University of Pennsylvania, Philadelphia, and his associates.

They first tested efflux capacity in serum samples from a cohort of 203 healthy white adults participating in a study of HDL-related biomarkers and atherosclerosis. These subjects underwent measurement of carotid artery intima-media thickness as part of that study.

There was no association between HDL level and subclinical CAD. In contrast, there was a significant inverse correlation between HDL cholesterol efflux capacity and subclinical CAD, which remained robust after the data were adjusted for HDL and apolipoprotein A-1 levels.

The investigators then assessed efflux capacity using serum samples from 793 white participants in a case-control cohort who underwent cardiac catheterization. The 442 patients found to have CAD showed significantly lower efflux capacity than did the 351 control subjects who were free of CAD.

In a further analysis, the proportion of patients with CAD decreased consistently with increasing efflux capacity. When the cohort was divided into quartiles of efflux capacity, the quartile with the highest efflux capacity showed a distinct decrease in CAD compared with the quartile with the lowest capacity.

All of these correlations remained robust after adjustment for subject age, sex, and traditional cardiovascular disease risk factors, Dr. Khera and his colleagues said (N. Engl. J. Med. 2010;364:127-35).

“Although cholesterol efflux from macrophages represents only a small fraction of overall flux through the reverse-cholesterol-transport pathway, it is probably the component that is most relevant to atheroprotection,” they noted.

“These findings reinforce the concept that assessment of HDL function” – not just HDL levels – “may prove informative in refining our understanding of HDL-mediated atheroprotection,” the researchers added.

This study was supported by the National Heart, Lung, and Blood Institute; the National Center for Research Resources; the Doris Duke Charitable Foundation; and the Howard Hughes Medical Institute. Dr. Khera's associates reported ties to Kinemed, Vascular Strategies, and GlaxoSmithKline, as well as involvement with a patent on cell culture systems for determining cholesterol efflux potential in serum.

View on the News

HDL Function Deserves Further Study

The central hypothesis of the study, which was based on findings from studies in animals and cell cultures, was that HDL promotes cholesterol efflux from macrophage foam cells in atheromatous vessels, thus decreasing both the cholesterol burden and macrophage-driven inflammation, said Dr. Jay Heinecke.

The results thus “provide important evidence that the ability of HDL to promote cholesterol efflux from macrophage foam cells is a key property that explains in part the inverse relationship between HDL and the risk of atherosclerotic coronary artery disease in humans.”

Measuring efflux capacity thus may become a useful tool in further investigation of HDL function as well as in developing treatments for CAD, he said.

DR. HEINECKE is with the University of Washington, Seattle. He reported ties to several drug and biomedical technology companies. These comments are taken from his editorial accompanying Dr. Khera's report (N. Engl. J. Med. 2010;364:170-1).

Major Finding: Only 14% of 4,218 individual recommendations in 41 Infectious Diseases Society of America clinical practice guidelines are based on level I evidence such as that from randomized clinical trials, while more than half are based on level III evidence, such as that from expert opinion or descriptive studies.

Data Source: A review of 41 current IDSA clinical practice guidelines aimed at assessing the quality of evidence on which each recommendation is based.

Disclosures: Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.

More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.

Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, Dr. Lee and Dr. Vielemeyer reported.

“Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data,” they noted.

“Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care.”

The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.

In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or “dramatic results from uncontrolled experiments” as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that “from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees,” the investigators said.

Dr. Lee and Dr. Vielemeyer identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendations and the quality of the evidence supporting them. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).

For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.

The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. “However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only,” Dr. Lee and Dr. Vielemeyer said.

In addition, “we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades,” they added.

These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also “as benchmarks in the appraisal of quality of care provision,” they said.

“We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.

“In such cases, we encourage reviewing the primary literature and using one's clinical judgment rather than relying solely on recommendations,” Dr. Lee and Dr. Vielemeyer concluded.

Major Finding: Only 14% of 4,218 individual recommendations in 41 Infectious Diseases Society of America clinical practice guidelines are based on level I evidence such as that from randomized clinical trials, while more than half are based on level III evidence, such as that from expert opinion or descriptive studies.

Data Source: A review of 41 current IDSA clinical practice guidelines aimed at assessing the quality of evidence on which each recommendation is based.

Disclosures: Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.

More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.

Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, Dr. Lee and Dr. Vielemeyer reported.

“Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data,” they noted.

“Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care.”

The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.

In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or “dramatic results from uncontrolled experiments” as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that “from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees,” the investigators said.

Dr. Lee and Dr. Vielemeyer identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendations and the quality of the evidence supporting them. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).

For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.

The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. “However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only,” Dr. Lee and Dr. Vielemeyer said.

In addition, “we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades,” they added.

These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also “as benchmarks in the appraisal of quality of care provision,” they said.

“We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.

“In such cases, we encourage reviewing the primary literature and using one's clinical judgment rather than relying solely on recommendations,” Dr. Lee and Dr. Vielemeyer concluded.

Major Finding: Only 14% of 4,218 individual recommendations in 41 Infectious Diseases Society of America clinical practice guidelines are based on level I evidence such as that from randomized clinical trials, while more than half are based on level III evidence, such as that from expert opinion or descriptive studies.

Data Source: A review of 41 current IDSA clinical practice guidelines aimed at assessing the quality of evidence on which each recommendation is based.

Disclosures: Dr. Lee and Dr. Vielemeyer reported that they had no relevant financial disclosures.

More than half of the current recommendations in practice guidelines concerning infectious disease are based on evidence derived only from expert opinion or descriptive studies, according to Dr. Dong Heun Lee and Dr. Ole Vielemeyer of Drexel University, Philadelphia.

Only 14% of the 4,218 individual recommendations included in 41 Infectious Diseases Society of America (IDSA) guidelines published in 1994-2010 are based on the highest-quality, or level I, evidence, such as that from randomized controlled trials, Dr. Lee and Dr. Vielemeyer reported.

“Guidelines can only summarize the best available evidence, which often may be weak. Thus, even more than 50 years since the inception of evidence-based medicine, following guidelines cannot always be equated with practicing medicine that is founded on robust data,” they noted.

“Physicians and policy makers should remain cautious when using current guidelines as the sole source guiding decisions in patient care.”

The study authors assessed the quality of evidence underlying 41 of the 52 IDSA guidelines currently available, which cover a wide range of topics and use an IDSA evidence-grading system. About half of these 41 guidelines are new and half are updates of earlier guidelines.

In addition to the highest-quality (level I) evidence, the IDSA grading system designates evidence from well-designed, but nonrandomized clinical trials, from cohort studies, from case-controlled analytical studies, or “dramatic results from uncontrolled experiments” as intermediate-quality (level II) evidence. The lowest-quality (level III) evidence is that “from the opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees,” the investigators said.

Dr. Lee and Dr. Vielemeyer identified 4,218 individual recommendations among the 41 guidelines that could be charted according to the strength of the recommendations and the quality of the evidence supporting them. Only 14% were supported by level I evidence, 31% by level II evidence, and 55% by level III evidence (Arch. Intern. Med. 2011;171:18-22).

For example, greater than 80% of the recommendations concerning blastomycosis, which were published in 2008, were based on level III evidence and did not have any level I support. The findings were the same for recommendations concerning sporotrichosis, which were published in 2007.

The investigators also assessed the extent to which the quality of evidence has improved over time by selecting five guidelines that had recently been updated and comparing them with their respective earlier versions. The updates did include evidence from more studies, as well as evidence from more recent studies, than did the earlier guidelines. “However, only two updated guidelines had a significant increase in the number of level I quality-of-evidence recommendations; most additional recommendations were supported by level II or III quality of evidence only,” Dr. Lee and Dr. Vielemeyer said.

In addition, “we came across imprecisions on more than one occasion and for more than one guideline, including illogical, erroneous, or missing references for recommendations and their associated grades,” they added.

These findings are particularly concerning because guidelines are used not only for decision making in clinical practice but also “as benchmarks in the appraisal of quality of care provision,” they said.

“We believe that the current clinical practice guidelines released by the IDSA constitute a great and reliable source of information that should be used. However, in circumstances when patient outcome is less than desirable, or when colleagues use diagnostic or therapeutic choices not included in the recommendations, it is prudent to remember that many of the individual recommendations are not supported by solid evidence.

“In such cases, we encourage reviewing the primary literature and using one's clinical judgment rather than relying solely on recommendations,” Dr. Lee and Dr. Vielemeyer concluded.

Major Finding: Of 161 treatment-naive patients, 109 had undetectable plasma levels of HCV RNA at weeks 4-20 and stopped treatment at 24 weeks (96% sustained virologic response), 29 patients with detectable HCV RNA continued the standard 48 weeks of treatment (79% sustained virologic response), and 33 patients dropped out.

Data Source: A multicenter, phase II, open-label study of telaprevir with ribavirin and peginterferon alfa-2a or 2b in treatment-naive patients aged 18-65 years with no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use.

Disclosures: The trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients who have chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as “the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor.”

The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, the Netherlands, and Spain, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-68.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin, who is with Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, Dr. Marcellin and his associates added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course, the investigators said.

This strategy of guiding treatment duration according to each patient's virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

“This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients,” Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. “Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing,” the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

Major Finding: Of 161 treatment-naive patients, 109 had undetectable plasma levels of HCV RNA at weeks 4-20 and stopped treatment at 24 weeks (96% sustained virologic response), 29 patients with detectable HCV RNA continued the standard 48 weeks of treatment (79% sustained virologic response), and 33 patients dropped out.

Data Source: A multicenter, phase II, open-label study of telaprevir with ribavirin and peginterferon alfa-2a or 2b in treatment-naive patients aged 18-65 years with no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use.

Disclosures: The trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients who have chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as “the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor.”

The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, the Netherlands, and Spain, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-68.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin, who is with Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, Dr. Marcellin and his associates added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course, the investigators said.

This strategy of guiding treatment duration according to each patient's virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

“This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients,” Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. “Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing,” the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

Major Finding: Of 161 treatment-naive patients, 109 had undetectable plasma levels of HCV RNA at weeks 4-20 and stopped treatment at 24 weeks (96% sustained virologic response), 29 patients with detectable HCV RNA continued the standard 48 weeks of treatment (79% sustained virologic response), and 33 patients dropped out.

Data Source: A multicenter, phase II, open-label study of telaprevir with ribavirin and peginterferon alfa-2a or 2b in treatment-naive patients aged 18-65 years with no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use.

Disclosures: The trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

In patients who have chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as “the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor.”

The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, the Netherlands, and Spain, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-68.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin, who is with Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, Dr. Marcellin and his associates added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course, the investigators said.

This strategy of guiding treatment duration according to each patient's virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

“This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients,” Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. “Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing,” the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

Major Finding: Children who attended large day-care programs before age 2 1/2 years had higher rates of respiratory and ear infections only around the time of enrollment, compared with those who were cared for at home or who attended small day-care programs. However, they had fewer respiratory and ear infections once in elementary school, so that the overall number of infections was similar among the three groups.

Data Source: Secondary analysis of data on 1,238 children participating in the Quebec Longitudinal Study of Child Development in 1998-2006.

Disclosures: This study was supported by the government of Quebec, Fondation Chagnon, Fond Québécois de la Recherche sur la Société et la Culture, Fonds pour la Recherche en Santé du Québec, Social Science and Humanities Research Council of Canada, Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the University of Montreal. No financial conflicts of interest were reported.

Children who attend large day-care programs before age 2 1/2 years show a short-term increase in the number of infections they acquire but are protected against infections during the elementary school years, according to a report.

“This study provides reassuring evidence for parents that their choices regarding child care (group size and age at enrollment) should not have a major effect on the health of their children from a long-term perspective, at least regarding respiratory tract infections, gastrointestinal tract infections, and ear infections,” said Sylvana M. Côté, Ph.D., of the department of social and preventive medicine, Ste-Justine Hospital, Montreal, and her associates.

“Physicians may reassure parents whose children initiate large group child care early that their child's experiencing infections is temporary and is likely to provide them with greater immunity during the elementary school years,” they noted.

Dr. Côté and her colleagues performed what they described as the first prospective, population-based study to examine the associations between different day-care experiences and three types of infections from early preschool age through mid-elementary school age. They used data from the Quebec Longitudinal Study of Child Development to follow a representative sample of 1,238 study subjects every year from 5 months of age in 1998 through 8 years of age in 2006.

The researchers statistically controlled for potentially confounding variables such as maternal education level, maternal health status, low birth weight, breast-feeding status, ethnicity, and family size.

In all, 244 children (approximately 20%) were cared for at home and did not attend day care of any size before enrolling in school. An additional 402 children (32%) attended a small, home-based day-care program for three to eight children younger than age 2 1/2, while 249 (20%) attended a large day-care program (up to 10 groups of 8-12 children per “class”) before age 2 1/2. The remaining children attended either small or large day-care programs after age 2 1/2.

Compared with home-cared children, those who started large day-care programs early in their preschool years had higher rates of respiratory and ear infections around the time they enrolled. However, they did not have higher rates of respiratory and ear infections at ages 3-4. More important, they had lower rates of such infections during the elementary school years, a time “when absenteeism carries more important consequences,” the investigators said (Arch. Pediatr. Adolesc. Med. 2010;164:1132-7).

Children who started large day-care programs later in their preschool years had higher rates of respiratory and ear infections at that time, but did not differ from home-cared children at any other time.

Children who started small day-care programs in either their early preschool years or late preschool years did not differ from home-cared children at any time. It thus appears that large day-care programs protect against future infections while small programs do not, perhaps because the large programs “provide exposure to a larger number of serotypes (and infectious agents) and … this wider exposure is necessary for preschoolers toacquire immunity,” they said.

Day care was not associated with gastrointestinal infections at any developmental period.

When the data were analyzed across the entire study period up to age 8 years, there was no difference in the overall number of infections between children who attended only home care before elementary school and children who attended either type of day care before elementary school.

Major Finding: Children who attended large day-care programs before age 2 1/2 years had higher rates of respiratory and ear infections only around the time of enrollment, compared with those who were cared for at home or who attended small day-care programs. However, they had fewer respiratory and ear infections once in elementary school, so that the overall number of infections was similar among the three groups.

Data Source: Secondary analysis of data on 1,238 children participating in the Quebec Longitudinal Study of Child Development in 1998-2006.

Disclosures: This study was supported by the government of Quebec, Fondation Chagnon, Fond Québécois de la Recherche sur la Société et la Culture, Fonds pour la Recherche en Santé du Québec, Social Science and Humanities Research Council of Canada, Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the University of Montreal. No financial conflicts of interest were reported.

Children who attend large day-care programs before age 2 1/2 years show a short-term increase in the number of infections they acquire but are protected against infections during the elementary school years, according to a report.

“This study provides reassuring evidence for parents that their choices regarding child care (group size and age at enrollment) should not have a major effect on the health of their children from a long-term perspective, at least regarding respiratory tract infections, gastrointestinal tract infections, and ear infections,” said Sylvana M. Côté, Ph.D., of the department of social and preventive medicine, Ste-Justine Hospital, Montreal, and her associates.

“Physicians may reassure parents whose children initiate large group child care early that their child's experiencing infections is temporary and is likely to provide them with greater immunity during the elementary school years,” they noted.

Dr. Côté and her colleagues performed what they described as the first prospective, population-based study to examine the associations between different day-care experiences and three types of infections from early preschool age through mid-elementary school age. They used data from the Quebec Longitudinal Study of Child Development to follow a representative sample of 1,238 study subjects every year from 5 months of age in 1998 through 8 years of age in 2006.

The researchers statistically controlled for potentially confounding variables such as maternal education level, maternal health status, low birth weight, breast-feeding status, ethnicity, and family size.

In all, 244 children (approximately 20%) were cared for at home and did not attend day care of any size before enrolling in school. An additional 402 children (32%) attended a small, home-based day-care program for three to eight children younger than age 2 1/2, while 249 (20%) attended a large day-care program (up to 10 groups of 8-12 children per “class”) before age 2 1/2. The remaining children attended either small or large day-care programs after age 2 1/2.

Compared with home-cared children, those who started large day-care programs early in their preschool years had higher rates of respiratory and ear infections around the time they enrolled. However, they did not have higher rates of respiratory and ear infections at ages 3-4. More important, they had lower rates of such infections during the elementary school years, a time “when absenteeism carries more important consequences,” the investigators said (Arch. Pediatr. Adolesc. Med. 2010;164:1132-7).

Children who started large day-care programs later in their preschool years had higher rates of respiratory and ear infections at that time, but did not differ from home-cared children at any other time.

Children who started small day-care programs in either their early preschool years or late preschool years did not differ from home-cared children at any time. It thus appears that large day-care programs protect against future infections while small programs do not, perhaps because the large programs “provide exposure to a larger number of serotypes (and infectious agents) and … this wider exposure is necessary for preschoolers toacquire immunity,” they said.

Day care was not associated with gastrointestinal infections at any developmental period.

When the data were analyzed across the entire study period up to age 8 years, there was no difference in the overall number of infections between children who attended only home care before elementary school and children who attended either type of day care before elementary school.

Major Finding: Children who attended large day-care programs before age 2 1/2 years had higher rates of respiratory and ear infections only around the time of enrollment, compared with those who were cared for at home or who attended small day-care programs. However, they had fewer respiratory and ear infections once in elementary school, so that the overall number of infections was similar among the three groups.

Data Source: Secondary analysis of data on 1,238 children participating in the Quebec Longitudinal Study of Child Development in 1998-2006.

Disclosures: This study was supported by the government of Quebec, Fondation Chagnon, Fond Québécois de la Recherche sur la Société et la Culture, Fonds pour la Recherche en Santé du Québec, Social Science and Humanities Research Council of Canada, Canadian Institutes for Health Research, Sainte-Justine Hospital's Research Center, and the University of Montreal. No financial conflicts of interest were reported.

Children who attend large day-care programs before age 2 1/2 years show a short-term increase in the number of infections they acquire but are protected against infections during the elementary school years, according to a report.

“This study provides reassuring evidence for parents that their choices regarding child care (group size and age at enrollment) should not have a major effect on the health of their children from a long-term perspective, at least regarding respiratory tract infections, gastrointestinal tract infections, and ear infections,” said Sylvana M. Côté, Ph.D., of the department of social and preventive medicine, Ste-Justine Hospital, Montreal, and her associates.

“Physicians may reassure parents whose children initiate large group child care early that their child's experiencing infections is temporary and is likely to provide them with greater immunity during the elementary school years,” they noted.

Dr. Côté and her colleagues performed what they described as the first prospective, population-based study to examine the associations between different day-care experiences and three types of infections from early preschool age through mid-elementary school age. They used data from the Quebec Longitudinal Study of Child Development to follow a representative sample of 1,238 study subjects every year from 5 months of age in 1998 through 8 years of age in 2006.

The researchers statistically controlled for potentially confounding variables such as maternal education level, maternal health status, low birth weight, breast-feeding status, ethnicity, and family size.

In all, 244 children (approximately 20%) were cared for at home and did not attend day care of any size before enrolling in school. An additional 402 children (32%) attended a small, home-based day-care program for three to eight children younger than age 2 1/2, while 249 (20%) attended a large day-care program (up to 10 groups of 8-12 children per “class”) before age 2 1/2. The remaining children attended either small or large day-care programs after age 2 1/2.

Compared with home-cared children, those who started large day-care programs early in their preschool years had higher rates of respiratory and ear infections around the time they enrolled. However, they did not have higher rates of respiratory and ear infections at ages 3-4. More important, they had lower rates of such infections during the elementary school years, a time “when absenteeism carries more important consequences,” the investigators said (Arch. Pediatr. Adolesc. Med. 2010;164:1132-7).

Children who started large day-care programs later in their preschool years had higher rates of respiratory and ear infections at that time, but did not differ from home-cared children at any other time.

Children who started small day-care programs in either their early preschool years or late preschool years did not differ from home-cared children at any time. It thus appears that large day-care programs protect against future infections while small programs do not, perhaps because the large programs “provide exposure to a larger number of serotypes (and infectious agents) and … this wider exposure is necessary for preschoolers toacquire immunity,” they said.

Day care was not associated with gastrointestinal infections at any developmental period.

When the data were analyzed across the entire study period up to age 8 years, there was no difference in the overall number of infections between children who attended only home care before elementary school and children who attended either type of day care before elementary school.

Consumers who typically pay $400-$2,000 to obtain their genetic risk profiles via the Internet appear to change very little after reading the results, at least in the short term, according to a new report.

In a prospective study involving 3,639 participants who chose to obtain direct-to-consumer, genomewide risk profiling with a commercially available test, there were no measurable changes in anxiety level, dietary fat intake, or exercise level –markers of change in health behavior – or in the use of screening tests for health disorders in the 3 months after they received their results.

In addition, only 10% of the subjects consulted with a genetic counselor, even though there was active outreach from the counselor and services were provided free of charge. A total of 26% reported sharing their results with their physician, according to Cinnamon S. Bloss, Ph.D., of Scripps Genomic Medicine and Scripps Health in La Jolla, Calif., and her associates.

The study participants are still being followed to track their longer-term psychological and behavioral responses during the next year. Meanwhile, "generally speaking, our findings support the null hypothesis (that provision of the results of a direct-to-consumer genomic risk test does not affect health-related behavior), but the potential effects on the population at large are still unknown," the investigators noted.

The clinical validity and utility of genomewide profiling have never been demonstrated. Proponents have argued that consumers who purchase the test may become more compliant with health-screening practices and adopt more healthful lifestyles. Opponents have argued that instead, such testing may raise consumers’ anxiety and boost their use of unnecessary and expensive medical screening and procedures.

To examine this issue, Dr. Bloss and her colleagues performed an ongoing, longitudinal, cohort study in which subjects were assessed at baseline and at 3 months to measure changes in their anxiety symptoms and behavior after profiling. All subjects purchased the genomewide risk profiles at a subsidized cost and were offered free genetic counseling in exchange for their participation.

Only 2,037 subjects completed the 3-month follow-up. A total of 55 completed the baseline health assessment but withdrew from the study, 223 never submitted a sample for genetic testing or never viewed their results, and 1,310 viewed their results but were lost to follow-up. "The failure of a large percentage of subjects (44%) to complete the study is notable," the researchers said.

"We found no evidence that learning the results of genomic risk testing had any short-term psychological, behavioral, or clinical effects on the study subjects," they said (N. Engl. J. Med. 2011 Jan. 12 [doi:10.1056/NEJMoa1011893]).

Overall, the participants showed no discernible change in anxiety level, according to measurements on the Impact of Events Scale–Revised or the Avoidance and Intrusion subscales of this anxiety-screening tool. More than 90% of subjects had low scores indicating no test-related distress, and more than 97% had low scores indicating no clinically significant test-related distress.

However, it is possible that subjects who may have been harmed psychologically by the testing are the ones who declined to participate in the first place, or who dropped out, Dr. Bloss and her associates noted.

The study subjects also showed no change in dietary fat intake or exercise level.

Subjects also did not pursue screening for a variety of disorders that their genetic profiles may have prompted, including thyroid testing, colonoscopy, cholesterol screening, cardiac stress testing, mammography, prostate-specific antigen testing, eye exams, or blood tests for numerous diseases that have a genetic component.

"This may be a good thing, given that the majority of the screening tests we assessed are considered inappropriate for asymptomatic persons. In most instances, the use of such tests would probably result in a waste of health care resources," the researchers said.

This study was limited in that it involved selected subjects and was of longitudinal design so it did not include a control group. Moreover, "the subjects in our study are clearly not representative of the broader U.S. population, and we therefore cannot draw conclusions about the effect of genomewide testing on the population at large," Dr. Bloss and her colleagues said.

Consumers who typically pay $400-$2,000 to obtain their genetic risk profiles via the Internet appear to change very little after reading the results, at least in the short term, according to a new report.

In a prospective study involving 3,639 participants who chose to obtain direct-to-consumer, genomewide risk profiling with a commercially available test, there were no measurable changes in anxiety level, dietary fat intake, or exercise level –markers of change in health behavior – or in the use of screening tests for health disorders in the 3 months after they received their results.

In addition, only 10% of the subjects consulted with a genetic counselor, even though there was active outreach from the counselor and services were provided free of charge. A total of 26% reported sharing their results with their physician, according to Cinnamon S. Bloss, Ph.D., of Scripps Genomic Medicine and Scripps Health in La Jolla, Calif., and her associates.

The study participants are still being followed to track their longer-term psychological and behavioral responses during the next year. Meanwhile, "generally speaking, our findings support the null hypothesis (that provision of the results of a direct-to-consumer genomic risk test does not affect health-related behavior), but the potential effects on the population at large are still unknown," the investigators noted.

The clinical validity and utility of genomewide profiling have never been demonstrated. Proponents have argued that consumers who purchase the test may become more compliant with health-screening practices and adopt more healthful lifestyles. Opponents have argued that instead, such testing may raise consumers’ anxiety and boost their use of unnecessary and expensive medical screening and procedures.

To examine this issue, Dr. Bloss and her colleagues performed an ongoing, longitudinal, cohort study in which subjects were assessed at baseline and at 3 months to measure changes in their anxiety symptoms and behavior after profiling. All subjects purchased the genomewide risk profiles at a subsidized cost and were offered free genetic counseling in exchange for their participation.

Only 2,037 subjects completed the 3-month follow-up. A total of 55 completed the baseline health assessment but withdrew from the study, 223 never submitted a sample for genetic testing or never viewed their results, and 1,310 viewed their results but were lost to follow-up. "The failure of a large percentage of subjects (44%) to complete the study is notable," the researchers said.

"We found no evidence that learning the results of genomic risk testing had any short-term psychological, behavioral, or clinical effects on the study subjects," they said (N. Engl. J. Med. 2011 Jan. 12 [doi:10.1056/NEJMoa1011893]).

Overall, the participants showed no discernible change in anxiety level, according to measurements on the Impact of Events Scale–Revised or the Avoidance and Intrusion subscales of this anxiety-screening tool. More than 90% of subjects had low scores indicating no test-related distress, and more than 97% had low scores indicating no clinically significant test-related distress.

However, it is possible that subjects who may have been harmed psychologically by the testing are the ones who declined to participate in the first place, or who dropped out, Dr. Bloss and her associates noted.

The study subjects also showed no change in dietary fat intake or exercise level.

Subjects also did not pursue screening for a variety of disorders that their genetic profiles may have prompted, including thyroid testing, colonoscopy, cholesterol screening, cardiac stress testing, mammography, prostate-specific antigen testing, eye exams, or blood tests for numerous diseases that have a genetic component.

"This may be a good thing, given that the majority of the screening tests we assessed are considered inappropriate for asymptomatic persons. In most instances, the use of such tests would probably result in a waste of health care resources," the researchers said.

This study was limited in that it involved selected subjects and was of longitudinal design so it did not include a control group. Moreover, "the subjects in our study are clearly not representative of the broader U.S. population, and we therefore cannot draw conclusions about the effect of genomewide testing on the population at large," Dr. Bloss and her colleagues said.

Consumers who typically pay $400-$2,000 to obtain their genetic risk profiles via the Internet appear to change very little after reading the results, at least in the short term, according to a new report.

In a prospective study involving 3,639 participants who chose to obtain direct-to-consumer, genomewide risk profiling with a commercially available test, there were no measurable changes in anxiety level, dietary fat intake, or exercise level –markers of change in health behavior – or in the use of screening tests for health disorders in the 3 months after they received their results.

In addition, only 10% of the subjects consulted with a genetic counselor, even though there was active outreach from the counselor and services were provided free of charge. A total of 26% reported sharing their results with their physician, according to Cinnamon S. Bloss, Ph.D., of Scripps Genomic Medicine and Scripps Health in La Jolla, Calif., and her associates.

The study participants are still being followed to track their longer-term psychological and behavioral responses during the next year. Meanwhile, "generally speaking, our findings support the null hypothesis (that provision of the results of a direct-to-consumer genomic risk test does not affect health-related behavior), but the potential effects on the population at large are still unknown," the investigators noted.

The clinical validity and utility of genomewide profiling have never been demonstrated. Proponents have argued that consumers who purchase the test may become more compliant with health-screening practices and adopt more healthful lifestyles. Opponents have argued that instead, such testing may raise consumers’ anxiety and boost their use of unnecessary and expensive medical screening and procedures.

To examine this issue, Dr. Bloss and her colleagues performed an ongoing, longitudinal, cohort study in which subjects were assessed at baseline and at 3 months to measure changes in their anxiety symptoms and behavior after profiling. All subjects purchased the genomewide risk profiles at a subsidized cost and were offered free genetic counseling in exchange for their participation.

Only 2,037 subjects completed the 3-month follow-up. A total of 55 completed the baseline health assessment but withdrew from the study, 223 never submitted a sample for genetic testing or never viewed their results, and 1,310 viewed their results but were lost to follow-up. "The failure of a large percentage of subjects (44%) to complete the study is notable," the researchers said.

"We found no evidence that learning the results of genomic risk testing had any short-term psychological, behavioral, or clinical effects on the study subjects," they said (N. Engl. J. Med. 2011 Jan. 12 [doi:10.1056/NEJMoa1011893]).

Overall, the participants showed no discernible change in anxiety level, according to measurements on the Impact of Events Scale–Revised or the Avoidance and Intrusion subscales of this anxiety-screening tool. More than 90% of subjects had low scores indicating no test-related distress, and more than 97% had low scores indicating no clinically significant test-related distress.

However, it is possible that subjects who may have been harmed psychologically by the testing are the ones who declined to participate in the first place, or who dropped out, Dr. Bloss and her associates noted.

The study subjects also showed no change in dietary fat intake or exercise level.

Subjects also did not pursue screening for a variety of disorders that their genetic profiles may have prompted, including thyroid testing, colonoscopy, cholesterol screening, cardiac stress testing, mammography, prostate-specific antigen testing, eye exams, or blood tests for numerous diseases that have a genetic component.

"This may be a good thing, given that the majority of the screening tests we assessed are considered inappropriate for asymptomatic persons. In most instances, the use of such tests would probably result in a waste of health care resources," the researchers said.

This study was limited in that it involved selected subjects and was of longitudinal design so it did not include a control group. Moreover, "the subjects in our study are clearly not representative of the broader U.S. population, and we therefore cannot draw conclusions about the effect of genomewide testing on the population at large," Dr. Bloss and her colleagues said.

A simple risk score calculated at hospital discharge helps predict which patients with acute pancreatitis are likely to require readmission, Dr. Tom Lee Whitlock and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

"With this information, a clinician may decide to delay discharge of a patient at high risk for readmission, increase the level of outpatient care, or schedule earlier clinic follow-up," the investigators said (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.017]).

Similarly, using this tool can reassure clinicians that they "can feel reasonably safe discharging" patients with low risk scores.

"Reducing the rates of early readmission in acute pancreatitis ultimately leads to improved overall care and may reduce overall health care costs," said Dr. Whitlock and his associates at Brigham and Women’s Hospital, Boston.

The investigators had recently reported results of another study in which the incidence of early readmission for patients hospitalized with acute pancreatitis was found to be 19%. They suspected that several risk factors observed in that study might be useful in predicting the need for early readmission, which could in turn improve clinical practice.

They then performed a retrospective cohort study of 248 adults admitted to their hospital between 2005 and 2007 with a wide spectrum of severity of acute pancreatitis, to determine which risk factors were predictive of readmission within 30 days of initial discharge. Patient factors that were considered included age, gender, race, insurance status, smoking status, body mass index, and alcohol intake.

Clinical factors that were considered included the presence or degree of hypoxia, leukocytosis, gastrointestinal symptoms, pain, pancreatic necrosis, fever, tachycardia, tachypnea, and hyper- or hypotension. The use of antibiotics, opiates, abdominal drains, and other invasive devices was assessed, as were the etiology of the pancreatitis and the patient’s length of hospital stay.

Five of these factors were found to significantly predict the need for readmission within 30 days of discharge: intolerance of a solid diet at discharge; GI symptoms of nausea, vomiting, or diarrhea at discharge; pancreatic necrosis; use of antibiotics at discharge; and pain at discharge.

Points were assigned to each of these five predictors, according to the degree to which they correlated with readmission. Based on the scoring system then devised, 39 patients (14%) were classified as being at high risk, with scores of 4 or more points. Two-thirds of the patients were classified as low risk, with scores of 0-1 points. And the remaining 47 patients (19%) were classified as moderate risk, with scores of 2-3 points.

A total of 68% of the high-risk group did require readmission, while only 6% of the low-risk group did.

The scoring system was then tested prospectively in a validation cohort of 198 patients hospitalized in 2008 and 2009.

Forty-seven patients (24%) were classified as high risk, and the rate of early readmission in this group was 68%, exactly the same as the rate found in the derivation cohort. A total of 112 patients (57%) was classified as low risk, and their rate of early readmission was only 5%.

The remaining 38 patients (20% of the entire group) were classified as moderate risk, and their rate of early readmission was 17%.

To help clinicians remember the five key risk factors, in order of importance, Dr. Whitlock and his colleagues proposed the pneumonic SNNAP, which stands for (GI) Symptoms, Nutrition, Necrosis, Antibiotics, and Pain. "This new scoring system may aid clinicians in their decisions regarding discharge planning for patients with acute pancreatitis," the researchers said.

The authors had no relevant conflicts of interest or disclosures.

A simple risk score calculated at hospital discharge helps predict which patients with acute pancreatitis are likely to require readmission, Dr. Tom Lee Whitlock and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

"With this information, a clinician may decide to delay discharge of a patient at high risk for readmission, increase the level of outpatient care, or schedule earlier clinic follow-up," the investigators said (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.017]).

Similarly, using this tool can reassure clinicians that they "can feel reasonably safe discharging" patients with low risk scores.

"Reducing the rates of early readmission in acute pancreatitis ultimately leads to improved overall care and may reduce overall health care costs," said Dr. Whitlock and his associates at Brigham and Women’s Hospital, Boston.

The investigators had recently reported results of another study in which the incidence of early readmission for patients hospitalized with acute pancreatitis was found to be 19%. They suspected that several risk factors observed in that study might be useful in predicting the need for early readmission, which could in turn improve clinical practice.

They then performed a retrospective cohort study of 248 adults admitted to their hospital between 2005 and 2007 with a wide spectrum of severity of acute pancreatitis, to determine which risk factors were predictive of readmission within 30 days of initial discharge. Patient factors that were considered included age, gender, race, insurance status, smoking status, body mass index, and alcohol intake.

Clinical factors that were considered included the presence or degree of hypoxia, leukocytosis, gastrointestinal symptoms, pain, pancreatic necrosis, fever, tachycardia, tachypnea, and hyper- or hypotension. The use of antibiotics, opiates, abdominal drains, and other invasive devices was assessed, as were the etiology of the pancreatitis and the patient’s length of hospital stay.

Five of these factors were found to significantly predict the need for readmission within 30 days of discharge: intolerance of a solid diet at discharge; GI symptoms of nausea, vomiting, or diarrhea at discharge; pancreatic necrosis; use of antibiotics at discharge; and pain at discharge.

Points were assigned to each of these five predictors, according to the degree to which they correlated with readmission. Based on the scoring system then devised, 39 patients (14%) were classified as being at high risk, with scores of 4 or more points. Two-thirds of the patients were classified as low risk, with scores of 0-1 points. And the remaining 47 patients (19%) were classified as moderate risk, with scores of 2-3 points.

A total of 68% of the high-risk group did require readmission, while only 6% of the low-risk group did.

The scoring system was then tested prospectively in a validation cohort of 198 patients hospitalized in 2008 and 2009.

Forty-seven patients (24%) were classified as high risk, and the rate of early readmission in this group was 68%, exactly the same as the rate found in the derivation cohort. A total of 112 patients (57%) was classified as low risk, and their rate of early readmission was only 5%.

The remaining 38 patients (20% of the entire group) were classified as moderate risk, and their rate of early readmission was 17%.

To help clinicians remember the five key risk factors, in order of importance, Dr. Whitlock and his colleagues proposed the pneumonic SNNAP, which stands for (GI) Symptoms, Nutrition, Necrosis, Antibiotics, and Pain. "This new scoring system may aid clinicians in their decisions regarding discharge planning for patients with acute pancreatitis," the researchers said.

The authors had no relevant conflicts of interest or disclosures.

A simple risk score calculated at hospital discharge helps predict which patients with acute pancreatitis are likely to require readmission, Dr. Tom Lee Whitlock and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

"With this information, a clinician may decide to delay discharge of a patient at high risk for readmission, increase the level of outpatient care, or schedule earlier clinic follow-up," the investigators said (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.017]).

Similarly, using this tool can reassure clinicians that they "can feel reasonably safe discharging" patients with low risk scores.

"Reducing the rates of early readmission in acute pancreatitis ultimately leads to improved overall care and may reduce overall health care costs," said Dr. Whitlock and his associates at Brigham and Women’s Hospital, Boston.

The investigators had recently reported results of another study in which the incidence of early readmission for patients hospitalized with acute pancreatitis was found to be 19%. They suspected that several risk factors observed in that study might be useful in predicting the need for early readmission, which could in turn improve clinical practice.

They then performed a retrospective cohort study of 248 adults admitted to their hospital between 2005 and 2007 with a wide spectrum of severity of acute pancreatitis, to determine which risk factors were predictive of readmission within 30 days of initial discharge. Patient factors that were considered included age, gender, race, insurance status, smoking status, body mass index, and alcohol intake.

Clinical factors that were considered included the presence or degree of hypoxia, leukocytosis, gastrointestinal symptoms, pain, pancreatic necrosis, fever, tachycardia, tachypnea, and hyper- or hypotension. The use of antibiotics, opiates, abdominal drains, and other invasive devices was assessed, as were the etiology of the pancreatitis and the patient’s length of hospital stay.

Five of these factors were found to significantly predict the need for readmission within 30 days of discharge: intolerance of a solid diet at discharge; GI symptoms of nausea, vomiting, or diarrhea at discharge; pancreatic necrosis; use of antibiotics at discharge; and pain at discharge.

Points were assigned to each of these five predictors, according to the degree to which they correlated with readmission. Based on the scoring system then devised, 39 patients (14%) were classified as being at high risk, with scores of 4 or more points. Two-thirds of the patients were classified as low risk, with scores of 0-1 points. And the remaining 47 patients (19%) were classified as moderate risk, with scores of 2-3 points.

A total of 68% of the high-risk group did require readmission, while only 6% of the low-risk group did.

The scoring system was then tested prospectively in a validation cohort of 198 patients hospitalized in 2008 and 2009.

Forty-seven patients (24%) were classified as high risk, and the rate of early readmission in this group was 68%, exactly the same as the rate found in the derivation cohort. A total of 112 patients (57%) was classified as low risk, and their rate of early readmission was only 5%.

The remaining 38 patients (20% of the entire group) were classified as moderate risk, and their rate of early readmission was 17%.

To help clinicians remember the five key risk factors, in order of importance, Dr. Whitlock and his colleagues proposed the pneumonic SNNAP, which stands for (GI) Symptoms, Nutrition, Necrosis, Antibiotics, and Pain. "This new scoring system may aid clinicians in their decisions regarding discharge planning for patients with acute pancreatitis," the researchers said.

The authors had no relevant conflicts of interest or disclosures.

A simple risk score calculated at hospital discharge helps predict which patients with acute pancreatitis are likely to require readmission, Dr. Tom Lee Whitlock and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

"With this information, a clinician may decide to delay discharge of a patient at high risk for readmission, increase the level of outpatient care, or schedule earlier clinic follow-up," the investigators said (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.017]).

Similarly, using this tool can reassure clinicians that they "can feel reasonably safe discharging" patients with low risk scores.

"Reducing the rates of early readmission in acute pancreatitis ultimately leads to improved overall care and may reduce overall health care costs," said Dr. Whitlock and his associates at Brigham and Women’s Hospital, Boston.

The investigators had recently reported results of another study in which the incidence of early readmission for patients hospitalized with acute pancreatitis was found to be 19%. They suspected that several risk factors observed in that study might be useful in predicting the need for early readmission, which could in turn improve clinical practice.

They then performed a retrospective cohort study of 248 adults admitted to their hospital between 2005 and 2007 with a wide spectrum of severity of acute pancreatitis, to determine which risk factors were predictive of readmission within 30 days of initial discharge. Patient factors that were considered included age, gender, race, insurance status, smoking status, body mass index, and alcohol intake.

Clinical factors that were considered included the presence or degree of hypoxia, leukocytosis, gastrointestinal symptoms, pain, pancreatic necrosis, fever, tachycardia, tachypnea, and hyper- or hypotension. The use of antibiotics, opiates, abdominal drains, and other invasive devices was assessed, as were the etiology of the pancreatitis and the patient’s length of hospital stay.

Five of these factors were found to significantly predict the need for readmission within 30 days of discharge: intolerance of a solid diet at discharge; GI symptoms of nausea, vomiting, or diarrhea at discharge; pancreatic necrosis; use of antibiotics at discharge; and pain at discharge.

Points were assigned to each of these five predictors, according to the degree to which they correlated with readmission. Based on the scoring system then devised, 39 patients (14%) were classified as being at high risk, with scores of 4 or more points. Two-thirds of the patients were classified as low risk, with scores of 0-1 points. And the remaining 47 patients (19%) were classified as moderate risk, with scores of 2-3 points.

A total of 68% of the high-risk group did require readmission, while only 6% of the low-risk group did.

The scoring system was then tested prospectively in a validation cohort of 198 patients hospitalized in 2008 and 2009.

Forty-seven patients (24%) were classified as high risk, and the rate of early readmission in this group was 68%, exactly the same as the rate found in the derivation cohort. A total of 112 patients (57%) was classified as low risk, and their rate of early readmission was only 5%.

The remaining 38 patients (20% of the entire group) were classified as moderate risk, and their rate of early readmission was 17%.

To help clinicians remember the five key risk factors, in order of importance, Dr. Whitlock and his colleagues proposed the pneumonic SNNAP, which stands for (GI) Symptoms, Nutrition, Necrosis, Antibiotics, and Pain. "This new scoring system may aid clinicians in their decisions regarding discharge planning for patients with acute pancreatitis," the researchers said.

The authors had no relevant conflicts of interest or disclosures.

A simple risk score calculated at hospital discharge helps predict which patients with acute pancreatitis are likely to require readmission, Dr. Tom Lee Whitlock and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

"With this information, a clinician may decide to delay discharge of a patient at high risk for readmission, increase the level of outpatient care, or schedule earlier clinic follow-up," the investigators said (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.017]).

Similarly, using this tool can reassure clinicians that they "can feel reasonably safe discharging" patients with low risk scores.

"Reducing the rates of early readmission in acute pancreatitis ultimately leads to improved overall care and may reduce overall health care costs," said Dr. Whitlock and his associates at Brigham and Women’s Hospital, Boston.

The investigators had recently reported results of another study in which the incidence of early readmission for patients hospitalized with acute pancreatitis was found to be 19%. They suspected that several risk factors observed in that study might be useful in predicting the need for early readmission, which could in turn improve clinical practice.

They then performed a retrospective cohort study of 248 adults admitted to their hospital between 2005 and 2007 with a wide spectrum of severity of acute pancreatitis, to determine which risk factors were predictive of readmission within 30 days of initial discharge. Patient factors that were considered included age, gender, race, insurance status, smoking status, body mass index, and alcohol intake.

Clinical factors that were considered included the presence or degree of hypoxia, leukocytosis, gastrointestinal symptoms, pain, pancreatic necrosis, fever, tachycardia, tachypnea, and hyper- or hypotension. The use of antibiotics, opiates, abdominal drains, and other invasive devices was assessed, as were the etiology of the pancreatitis and the patient’s length of hospital stay.

Five of these factors were found to significantly predict the need for readmission within 30 days of discharge: intolerance of a solid diet at discharge; GI symptoms of nausea, vomiting, or diarrhea at discharge; pancreatic necrosis; use of antibiotics at discharge; and pain at discharge.

Points were assigned to each of these five predictors, according to the degree to which they correlated with readmission. Based on the scoring system then devised, 39 patients (14%) were classified as being at high risk, with scores of 4 or more points. Two-thirds of the patients were classified as low risk, with scores of 0-1 points. And the remaining 47 patients (19%) were classified as moderate risk, with scores of 2-3 points.

A total of 68% of the high-risk group did require readmission, while only 6% of the low-risk group did.

The scoring system was then tested prospectively in a validation cohort of 198 patients hospitalized in 2008 and 2009.

Forty-seven patients (24%) were classified as high risk, and the rate of early readmission in this group was 68%, exactly the same as the rate found in the derivation cohort. A total of 112 patients (57%) was classified as low risk, and their rate of early readmission was only 5%.

The remaining 38 patients (20% of the entire group) were classified as moderate risk, and their rate of early readmission was 17%.

To help clinicians remember the five key risk factors, in order of importance, Dr. Whitlock and his colleagues proposed the pneumonic SNNAP, which stands for (GI) Symptoms, Nutrition, Necrosis, Antibiotics, and Pain. "This new scoring system may aid clinicians in their decisions regarding discharge planning for patients with acute pancreatitis," the researchers said.

The authors had no relevant conflicts of interest or disclosures.

A simple risk score calculated at hospital discharge helps predict which patients with acute pancreatitis are likely to require readmission, Dr. Tom Lee Whitlock and his colleagues reported in the February issue of Clinical Gastroenterology and Hepatology.

"With this information, a clinician may decide to delay discharge of a patient at high risk for readmission, increase the level of outpatient care, or schedule earlier clinic follow-up," the investigators said (Clin. Gastroenterol. Hepatol. 2011 February [doi:10.1016/j.cgh.2010.08.017]).

Similarly, using this tool can reassure clinicians that they "can feel reasonably safe discharging" patients with low risk scores.

"Reducing the rates of early readmission in acute pancreatitis ultimately leads to improved overall care and may reduce overall health care costs," said Dr. Whitlock and his associates at Brigham and Women’s Hospital, Boston.

The investigators had recently reported results of another study in which the incidence of early readmission for patients hospitalized with acute pancreatitis was found to be 19%. They suspected that several risk factors observed in that study might be useful in predicting the need for early readmission, which could in turn improve clinical practice.

They then performed a retrospective cohort study of 248 adults admitted to their hospital between 2005 and 2007 with a wide spectrum of severity of acute pancreatitis, to determine which risk factors were predictive of readmission within 30 days of initial discharge. Patient factors that were considered included age, gender, race, insurance status, smoking status, body mass index, and alcohol intake.

Clinical factors that were considered included the presence or degree of hypoxia, leukocytosis, gastrointestinal symptoms, pain, pancreatic necrosis, fever, tachycardia, tachypnea, and hyper- or hypotension. The use of antibiotics, opiates, abdominal drains, and other invasive devices was assessed, as were the etiology of the pancreatitis and the patient’s length of hospital stay.

Five of these factors were found to significantly predict the need for readmission within 30 days of discharge: intolerance of a solid diet at discharge; GI symptoms of nausea, vomiting, or diarrhea at discharge; pancreatic necrosis; use of antibiotics at discharge; and pain at discharge.

Points were assigned to each of these five predictors, according to the degree to which they correlated with readmission. Based on the scoring system then devised, 39 patients (14%) were classified as being at high risk, with scores of 4 or more points. Two-thirds of the patients were classified as low risk, with scores of 0-1 points. And the remaining 47 patients (19%) were classified as moderate risk, with scores of 2-3 points.

A total of 68% of the high-risk group did require readmission, while only 6% of the low-risk group did.

The scoring system was then tested prospectively in a validation cohort of 198 patients hospitalized in 2008 and 2009.

Forty-seven patients (24%) were classified as high risk, and the rate of early readmission in this group was 68%, exactly the same as the rate found in the derivation cohort. A total of 112 patients (57%) was classified as low risk, and their rate of early readmission was only 5%.

The remaining 38 patients (20% of the entire group) were classified as moderate risk, and their rate of early readmission was 17%.

To help clinicians remember the five key risk factors, in order of importance, Dr. Whitlock and his colleagues proposed the pneumonic SNNAP, which stands for (GI) Symptoms, Nutrition, Necrosis, Antibiotics, and Pain. "This new scoring system may aid clinicians in their decisions regarding discharge planning for patients with acute pancreatitis," the researchers said.

The authors had no relevant conflicts of interest or disclosures.

New guidelines for managing extracranial carotid and vertebral artery disease recommend against routine screening for obstruction, and advocate ultrasound examination only in patients who are symptomatic or have at least risk two factors for stroke.

The guidelines also state that based on current evidence, carotid endarterectomy and carotid stenting appear to be equally "reasonable and safe" for patients found to have more than 50% blockage, with the choice between the two approaches dictated by individual factors such as patient anatomy, comorbidities, and stroke risk, wrote cochairs Dr. Jonathan L. Halperin, professor of medicine at Mount Sinai School of Medicine, New York, and Dr. Thomas G. Brott, professor of neurology and director of research at the Mayo Clinic, Jacksonville, Fla., and their colleagues on the writing committee.

The new guidelines, issued jointly by the American Heart Association, American Stroke Association, American College of Cardiology, and other expert groups, "are intended to assist the diverse array of clinicians who provide care for patients with ECVD [extracranial carotid and vertebral artery disease]" and include a comprehensive review of the most recent literature. They detail dozens of recommendations for diagnostic testing, treatment of contributing factors such as hypertension and hyperlipidemia, selecting patients for carotid revascularization, managing restenosis, and handling anatomic abnormalities and special patient populations (J. Am. Coll. Cardiol. 2011 [doi.10.1016/j.jacc.2010.11005]).

Among these recommendations:

• Duplex ultrasonography is the initial diagnostic test of choice for detecting hemodynamically significant carotid stenosis. It is "reasonable" to use this technique in asymptomatic patients if they have a carotid bruit; symptomatic coronary artery disease, peripheral artery disease, or atherosclerotic aortic aneurysm; or at least two of the following risk factors: hypertension, hyperlipidemia, smoking, family history of atherosclerosis manifested before age 60, and family history of ischemic stroke.

• Carotid stenting and carotid endarterectomy are similarly safe for treating obstructions of 50% or more. Physicians and patients should decide between the two procedures on an individual basis, taking into account surgical risk, comorbidities, life expectancy, patient preferences, neck anatomy, and other factors.

• "The value of specific therapies to prevent stroke, even in symptomatic patients with severe carotid artery stenosis, largely lacks validation." Antiplatelet therapy reduces stroke risk in patients with transient ischemic attack or previous stroke, but "no adequately powered studies have demonstrated their efficacy for stroke prevention in asymptomatic patients with ECVD." Similarly, the use of anticoagulants in ECVD patients who develop stroke has not been explored.

• It remains unclear whether women benefit as much as men do from carotid endarterectomy. Information also is lacking for other important subsets of patients, including the elderly and various racial/ethnic groups.

• "The most pressing question is how either technique of revascularization compares with intensive contemporary medical therapy, particularly among asymptomatic patients." A clinical trial that directly compares the three approaches "should include a sufficiently broad range of patients to permit meaningful analysis of subgroups based on age, sex, ethnicity, and risk status."

Regarding vertebral artery disease, the guidelines state that its infrequency relative to carotid artery disease has made for "huge gaps in knowledge." Registries to capture data on the prevalence, pathophysiology, prognosis, and natural history of vertebral artery disease would be an important first step in addressing these gaps, the authors noted.

The executive summary and full guidelines are available on the websites of the American College of Cardiology and the American Heart Association, and they are also being co-published in Circulation, Catheterization and Cardiovascular Interventions, the Journal of Cardiovascular Computed Tomography, the Journal of NeuroInterventional Surgery, the Journal of Vascular Surgery, and Vascular Medicine.

Most of the members of the writing committee disclosed ties to pharmaceutical and/or device companies. A complete list of those relations, and those of the peer reviewers, is in the executive summary.

New guidelines for managing extracranial carotid and vertebral artery disease recommend against routine screening for obstruction, and advocate ultrasound examination only in patients who are symptomatic or have at least risk two factors for stroke.

The guidelines also state that based on current evidence, carotid endarterectomy and carotid stenting appear to be equally "reasonable and safe" for patients found to have more than 50% blockage, with the choice between the two approaches dictated by individual factors such as patient anatomy, comorbidities, and stroke risk, wrote cochairs Dr. Jonathan L. Halperin, professor of medicine at Mount Sinai School of Medicine, New York, and Dr. Thomas G. Brott, professor of neurology and director of research at the Mayo Clinic, Jacksonville, Fla., and their colleagues on the writing committee.

The new guidelines, issued jointly by the American Heart Association, American Stroke Association, American College of Cardiology, and other expert groups, "are intended to assist the diverse array of clinicians who provide care for patients with ECVD [extracranial carotid and vertebral artery disease]" and include a comprehensive review of the most recent literature. They detail dozens of recommendations for diagnostic testing, treatment of contributing factors such as hypertension and hyperlipidemia, selecting patients for carotid revascularization, managing restenosis, and handling anatomic abnormalities and special patient populations (J. Am. Coll. Cardiol. 2011 [doi.10.1016/j.jacc.2010.11005]).

Among these recommendations:

• Duplex ultrasonography is the initial diagnostic test of choice for detecting hemodynamically significant carotid stenosis. It is "reasonable" to use this technique in asymptomatic patients if they have a carotid bruit; symptomatic coronary artery disease, peripheral artery disease, or atherosclerotic aortic aneurysm; or at least two of the following risk factors: hypertension, hyperlipidemia, smoking, family history of atherosclerosis manifested before age 60, and family history of ischemic stroke.

• Carotid stenting and carotid endarterectomy are similarly safe for treating obstructions of 50% or more. Physicians and patients should decide between the two procedures on an individual basis, taking into account surgical risk, comorbidities, life expectancy, patient preferences, neck anatomy, and other factors.

• "The value of specific therapies to prevent stroke, even in symptomatic patients with severe carotid artery stenosis, largely lacks validation." Antiplatelet therapy reduces stroke risk in patients with transient ischemic attack or previous stroke, but "no adequately powered studies have demonstrated their efficacy for stroke prevention in asymptomatic patients with ECVD." Similarly, the use of anticoagulants in ECVD patients who develop stroke has not been explored.

• It remains unclear whether women benefit as much as men do from carotid endarterectomy. Information also is lacking for other important subsets of patients, including the elderly and various racial/ethnic groups.

• "The most pressing question is how either technique of revascularization compares with intensive contemporary medical therapy, particularly among asymptomatic patients." A clinical trial that directly compares the three approaches "should include a sufficiently broad range of patients to permit meaningful analysis of subgroups based on age, sex, ethnicity, and risk status."

Regarding vertebral artery disease, the guidelines state that its infrequency relative to carotid artery disease has made for "huge gaps in knowledge." Registries to capture data on the prevalence, pathophysiology, prognosis, and natural history of vertebral artery disease would be an important first step in addressing these gaps, the authors noted.

The executive summary and full guidelines are available on the websites of the American College of Cardiology and the American Heart Association, and they are also being co-published in Circulation, Catheterization and Cardiovascular Interventions, the Journal of Cardiovascular Computed Tomography, the Journal of NeuroInterventional Surgery, the Journal of Vascular Surgery, and Vascular Medicine.

Most of the members of the writing committee disclosed ties to pharmaceutical and/or device companies. A complete list of those relations, and those of the peer reviewers, is in the executive summary.

New guidelines for managing extracranial carotid and vertebral artery disease recommend against routine screening for obstruction, and advocate ultrasound examination only in patients who are symptomatic or have at least risk two factors for stroke.

The guidelines also state that based on current evidence, carotid endarterectomy and carotid stenting appear to be equally "reasonable and safe" for patients found to have more than 50% blockage, with the choice between the two approaches dictated by individual factors such as patient anatomy, comorbidities, and stroke risk, wrote cochairs Dr. Jonathan L. Halperin, professor of medicine at Mount Sinai School of Medicine, New York, and Dr. Thomas G. Brott, professor of neurology and director of research at the Mayo Clinic, Jacksonville, Fla., and their colleagues on the writing committee.

The new guidelines, issued jointly by the American Heart Association, American Stroke Association, American College of Cardiology, and other expert groups, "are intended to assist the diverse array of clinicians who provide care for patients with ECVD [extracranial carotid and vertebral artery disease]" and include a comprehensive review of the most recent literature. They detail dozens of recommendations for diagnostic testing, treatment of contributing factors such as hypertension and hyperlipidemia, selecting patients for carotid revascularization, managing restenosis, and handling anatomic abnormalities and special patient populations (J. Am. Coll. Cardiol. 2011 [doi.10.1016/j.jacc.2010.11005]).

Among these recommendations:

• Duplex ultrasonography is the initial diagnostic test of choice for detecting hemodynamically significant carotid stenosis. It is "reasonable" to use this technique in asymptomatic patients if they have a carotid bruit; symptomatic coronary artery disease, peripheral artery disease, or atherosclerotic aortic aneurysm; or at least two of the following risk factors: hypertension, hyperlipidemia, smoking, family history of atherosclerosis manifested before age 60, and family history of ischemic stroke.

• Carotid stenting and carotid endarterectomy are similarly safe for treating obstructions of 50% or more. Physicians and patients should decide between the two procedures on an individual basis, taking into account surgical risk, comorbidities, life expectancy, patient preferences, neck anatomy, and other factors.

• "The value of specific therapies to prevent stroke, even in symptomatic patients with severe carotid artery stenosis, largely lacks validation." Antiplatelet therapy reduces stroke risk in patients with transient ischemic attack or previous stroke, but "no adequately powered studies have demonstrated their efficacy for stroke prevention in asymptomatic patients with ECVD." Similarly, the use of anticoagulants in ECVD patients who develop stroke has not been explored.

• It remains unclear whether women benefit as much as men do from carotid endarterectomy. Information also is lacking for other important subsets of patients, including the elderly and various racial/ethnic groups.

• "The most pressing question is how either technique of revascularization compares with intensive contemporary medical therapy, particularly among asymptomatic patients." A clinical trial that directly compares the three approaches "should include a sufficiently broad range of patients to permit meaningful analysis of subgroups based on age, sex, ethnicity, and risk status."

Regarding vertebral artery disease, the guidelines state that its infrequency relative to carotid artery disease has made for "huge gaps in knowledge." Registries to capture data on the prevalence, pathophysiology, prognosis, and natural history of vertebral artery disease would be an important first step in addressing these gaps, the authors noted.

The executive summary and full guidelines are available on the websites of the American College of Cardiology and the American Heart Association, and they are also being co-published in Circulation, Catheterization and Cardiovascular Interventions, the Journal of Cardiovascular Computed Tomography, the Journal of NeuroInterventional Surgery, the Journal of Vascular Surgery, and Vascular Medicine.

Most of the members of the writing committee disclosed ties to pharmaceutical and/or device companies. A complete list of those relations, and those of the peer reviewers, is in the executive summary.