Mitchel L. Zoler, PhD

ORLANDO — Bariatric surgery produces rapid, dramatic improvements in obese adolescents, but after the first 6 months post surgery these patients appear to hit a wall and further gains in their clinical status usually do not occur, according to a follow-up study of 44 patients.

“There is generally a plateau [of weight loss] at about 6-12 months, and sometimes a creep-up after 1 year. Even though [these adolescents] are significantly better, they're still not normal, so we should intervene even sooner,” Dr. Holly M. Ippisch said at the annual scientific sessions of the American Heart Association.

In a series of 87 adolescents who underwent Roux-en-Y bariatric surgery at Cincinnati Children's Hospital Medical Center, average body mass index dropped from 58 kg/m

Cardiovascular measures showed a similar pattern, with substantial improvements in parameters such as left ventricular mass and diastolic dysfunction during the first 6 months after surgery, followed by a leveling off to values that remained abnormally high and potentially dangerous.

“Even though it significantly improves [compared with baseline], it is still abnormal. It raises the issue of whether we should intervene [with bariatric surgery] sooner [in very obese adolescents], before they get beyond a certain point,” she said.

Diminishing weight loss more than 6 months out from surgery “is very interesting and is being seen at a number of U.S. centers” that are doing bariatric surgery on adolescents, said Dr. Stephen R. Daniels, a pediatric cardiologist and professor and chairman of pediatrics at the University of Colorado in Denver.

“It's something that we don't understand and need to learn more about. From what we can tell they are in general eating in a healthy way. There probably is some plateauing in adults, too, but many of them get bariatric surgery at a healthier state [a lower body mass index], so they often get down to a body mass index that is closer to normal,” he said in an interview.

At Cincinnati Children's and other centers, adolescents who are candidates for bariatric surgery must have a body mass index of at least 40 kg/m

To qualify without a serious comorbidity, their body mass index has to be at least 50 kg/m

When bariatric surgery for adolescents began a few years ago, “the thought was to be as conservative as possible, and reserve it for only the most severely affected adolescents,” Dr. Daniels added.

“We didn't know if it was safe for adolescents, so it was reserved for extreme cases,” Dr. Ippisch said.

But the plateauing effect now being widely seen “is starting a thought process on what the criteria should be,” Dr. Daniels said.

The 87 adolescents who underwent Roux-en-Y surgery in Cincinnati were aged 13-19 years, and three-quarters were girls.

Their average left ventricular mass at baseline was 52 g/m

Another way that Dr. Ippisch assessed left ventricular size and shape was to divide patients into four risk categories: normal (low-risk), concentric remodeling (mildly elevated risk), eccentric ventricular hypertrophy (moderately elevated risk), and concentric ventricular hypertrophy (highest risk).

The patients showed a shift overall, from half having normal-shaped hearts at baseline to about 80% with normal shapes at 6, 12, and 24 months' follow-up. (See box.)

The patients also had an elevated left ventricular end diastolic pressure at baseline and an average mitral E/Ea ratio of about 7.0, indicating diastolic dysfunction, that improved to an average ratio of about 6.0 after 6 months and remained at that level through 2 years of follow-up.

Other improvements included heart rate, which fell from an average of 83 bpm at baseline to 63 bpm at 6 months and 61 bpm at 2 years, and blood pressure, which dropped from an average of 121/69 mm Hg at baseline to an average of 113/65 mm Hg at 6 months and 114/66 mm Hg at 2 years.

Disclosures: Dr. Ippisch had no commercial financial disclosures related to this study.

Cardiovascular parameters leveled off to abnormally high and potentially dangerous values.

Source DR. IPPISCH

Source Elsevier Global Medical News

ORLANDO — Bariatric surgery produces rapid, dramatic improvements in obese adolescents, but after the first 6 months post surgery these patients appear to hit a wall and further gains in their clinical status usually do not occur, according to a follow-up study of 44 patients.

“There is generally a plateau [of weight loss] at about 6-12 months, and sometimes a creep-up after 1 year. Even though [these adolescents] are significantly better, they're still not normal, so we should intervene even sooner,” Dr. Holly M. Ippisch said at the annual scientific sessions of the American Heart Association.

In a series of 87 adolescents who underwent Roux-en-Y bariatric surgery at Cincinnati Children's Hospital Medical Center, average body mass index dropped from 58 kg/m

Cardiovascular measures showed a similar pattern, with substantial improvements in parameters such as left ventricular mass and diastolic dysfunction during the first 6 months after surgery, followed by a leveling off to values that remained abnormally high and potentially dangerous.

“Even though it significantly improves [compared with baseline], it is still abnormal. It raises the issue of whether we should intervene [with bariatric surgery] sooner [in very obese adolescents], before they get beyond a certain point,” she said.

Diminishing weight loss more than 6 months out from surgery “is very interesting and is being seen at a number of U.S. centers” that are doing bariatric surgery on adolescents, said Dr. Stephen R. Daniels, a pediatric cardiologist and professor and chairman of pediatrics at the University of Colorado in Denver.

“It's something that we don't understand and need to learn more about. From what we can tell they are in general eating in a healthy way. There probably is some plateauing in adults, too, but many of them get bariatric surgery at a healthier state [a lower body mass index], so they often get down to a body mass index that is closer to normal,” he said in an interview.

At Cincinnati Children's and other centers, adolescents who are candidates for bariatric surgery must have a body mass index of at least 40 kg/m

To qualify without a serious comorbidity, their body mass index has to be at least 50 kg/m

When bariatric surgery for adolescents began a few years ago, “the thought was to be as conservative as possible, and reserve it for only the most severely affected adolescents,” Dr. Daniels added.

“We didn't know if it was safe for adolescents, so it was reserved for extreme cases,” Dr. Ippisch said.

But the plateauing effect now being widely seen “is starting a thought process on what the criteria should be,” Dr. Daniels said.

The 87 adolescents who underwent Roux-en-Y surgery in Cincinnati were aged 13-19 years, and three-quarters were girls.

Their average left ventricular mass at baseline was 52 g/m

Another way that Dr. Ippisch assessed left ventricular size and shape was to divide patients into four risk categories: normal (low-risk), concentric remodeling (mildly elevated risk), eccentric ventricular hypertrophy (moderately elevated risk), and concentric ventricular hypertrophy (highest risk).

The patients showed a shift overall, from half having normal-shaped hearts at baseline to about 80% with normal shapes at 6, 12, and 24 months' follow-up. (See box.)

The patients also had an elevated left ventricular end diastolic pressure at baseline and an average mitral E/Ea ratio of about 7.0, indicating diastolic dysfunction, that improved to an average ratio of about 6.0 after 6 months and remained at that level through 2 years of follow-up.

Other improvements included heart rate, which fell from an average of 83 bpm at baseline to 63 bpm at 6 months and 61 bpm at 2 years, and blood pressure, which dropped from an average of 121/69 mm Hg at baseline to an average of 113/65 mm Hg at 6 months and 114/66 mm Hg at 2 years.

Disclosures: Dr. Ippisch had no commercial financial disclosures related to this study.

Cardiovascular parameters leveled off to abnormally high and potentially dangerous values.

Source DR. IPPISCH

Source Elsevier Global Medical News

ORLANDO — Bariatric surgery produces rapid, dramatic improvements in obese adolescents, but after the first 6 months post surgery these patients appear to hit a wall and further gains in their clinical status usually do not occur, according to a follow-up study of 44 patients.

“There is generally a plateau [of weight loss] at about 6-12 months, and sometimes a creep-up after 1 year. Even though [these adolescents] are significantly better, they're still not normal, so we should intervene even sooner,” Dr. Holly M. Ippisch said at the annual scientific sessions of the American Heart Association.

In a series of 87 adolescents who underwent Roux-en-Y bariatric surgery at Cincinnati Children's Hospital Medical Center, average body mass index dropped from 58 kg/m

Cardiovascular measures showed a similar pattern, with substantial improvements in parameters such as left ventricular mass and diastolic dysfunction during the first 6 months after surgery, followed by a leveling off to values that remained abnormally high and potentially dangerous.

“Even though it significantly improves [compared with baseline], it is still abnormal. It raises the issue of whether we should intervene [with bariatric surgery] sooner [in very obese adolescents], before they get beyond a certain point,” she said.

Diminishing weight loss more than 6 months out from surgery “is very interesting and is being seen at a number of U.S. centers” that are doing bariatric surgery on adolescents, said Dr. Stephen R. Daniels, a pediatric cardiologist and professor and chairman of pediatrics at the University of Colorado in Denver.

“It's something that we don't understand and need to learn more about. From what we can tell they are in general eating in a healthy way. There probably is some plateauing in adults, too, but many of them get bariatric surgery at a healthier state [a lower body mass index], so they often get down to a body mass index that is closer to normal,” he said in an interview.

At Cincinnati Children's and other centers, adolescents who are candidates for bariatric surgery must have a body mass index of at least 40 kg/m

To qualify without a serious comorbidity, their body mass index has to be at least 50 kg/m

When bariatric surgery for adolescents began a few years ago, “the thought was to be as conservative as possible, and reserve it for only the most severely affected adolescents,” Dr. Daniels added.

“We didn't know if it was safe for adolescents, so it was reserved for extreme cases,” Dr. Ippisch said.

But the plateauing effect now being widely seen “is starting a thought process on what the criteria should be,” Dr. Daniels said.

The 87 adolescents who underwent Roux-en-Y surgery in Cincinnati were aged 13-19 years, and three-quarters were girls.

Their average left ventricular mass at baseline was 52 g/m

Another way that Dr. Ippisch assessed left ventricular size and shape was to divide patients into four risk categories: normal (low-risk), concentric remodeling (mildly elevated risk), eccentric ventricular hypertrophy (moderately elevated risk), and concentric ventricular hypertrophy (highest risk).

The patients showed a shift overall, from half having normal-shaped hearts at baseline to about 80% with normal shapes at 6, 12, and 24 months' follow-up. (See box.)

The patients also had an elevated left ventricular end diastolic pressure at baseline and an average mitral E/Ea ratio of about 7.0, indicating diastolic dysfunction, that improved to an average ratio of about 6.0 after 6 months and remained at that level through 2 years of follow-up.

Other improvements included heart rate, which fell from an average of 83 bpm at baseline to 63 bpm at 6 months and 61 bpm at 2 years, and blood pressure, which dropped from an average of 121/69 mm Hg at baseline to an average of 113/65 mm Hg at 6 months and 114/66 mm Hg at 2 years.

Disclosures: Dr. Ippisch had no commercial financial disclosures related to this study.

Cardiovascular parameters leveled off to abnormally high and potentially dangerous values.

Source DR. IPPISCH

Source Elsevier Global Medical News

Major Findings: Survival to adulthood has significantly improved for persons born with congenital heart disease, from 82% in those born in the 1970s to 89% in those born in the 1990s.

Data Source: Clinical database of 17,044 patients in the congenital heart disease program at Catholic University, Leuven, Belgium.

Disclosures: Dr. Moons had no financial conflicts of interest to report.

ORLANDO — Infants born with a congenital heart disease during 1990-1999 who underwent care at a tertiary center had an 89% actuarial survival rate to age 18 or older, data on more than 3,800 patients at one Belgium center showed.

That was a significant improvement over 85% survival to adulthood for infants born during 1980-1989 and managed at the same center, and the 82% rate in those born during 1970-1979, Philip Moons, Ph.D., said at the annual scientific sessions of the American Heart Association.

The 89% rate improved on the 85% rate from the 32nd Bethesda Conference in a report based on outcomes of congenital heart disease patients born in the 1980s, Dr. Moon said (J. Am. Coll. Cardiol. 2001;37:1170-5).

Dr. Moons and his associates analyzed survival data from the clinical database of the congenital heart disease program at Catholic University, Leuven, Belgium. It included 17,044 patients born with gross structural abnormalities of the heart or intrathoracic great vessels with actual or potential functional significance. The subset of these patients born during 1990-1999 was 23%; 24% were born before 1970, 10% during 1970-1979, 21% during 1980-1989, and 17% in 2000 or later.

The most common congenital diseases for the entire group was ventricular septal defect (22%), followed by atrial septal defect (15%), and pulmonary valve abnormality (10%).

Among infants born in 1990-1999, mortality from congenital heart disease was due to cardiac failure in 56%, postoperative complications in 22%, and perioperative complications in 9%. In the 1990-1999 subgroup, survival during follow-up was 99% in patients with mild congenital heart disease, 90% in those with moderate disease, and 59% in patients with a complex abnormality, said Dr. Moons, a health services researcher at Catholic University.

Major Findings: Survival to adulthood has significantly improved for persons born with congenital heart disease, from 82% in those born in the 1970s to 89% in those born in the 1990s.

Data Source: Clinical database of 17,044 patients in the congenital heart disease program at Catholic University, Leuven, Belgium.

Disclosures: Dr. Moons had no financial conflicts of interest to report.

ORLANDO — Infants born with a congenital heart disease during 1990-1999 who underwent care at a tertiary center had an 89% actuarial survival rate to age 18 or older, data on more than 3,800 patients at one Belgium center showed.

That was a significant improvement over 85% survival to adulthood for infants born during 1980-1989 and managed at the same center, and the 82% rate in those born during 1970-1979, Philip Moons, Ph.D., said at the annual scientific sessions of the American Heart Association.

The 89% rate improved on the 85% rate from the 32nd Bethesda Conference in a report based on outcomes of congenital heart disease patients born in the 1980s, Dr. Moon said (J. Am. Coll. Cardiol. 2001;37:1170-5).

Dr. Moons and his associates analyzed survival data from the clinical database of the congenital heart disease program at Catholic University, Leuven, Belgium. It included 17,044 patients born with gross structural abnormalities of the heart or intrathoracic great vessels with actual or potential functional significance. The subset of these patients born during 1990-1999 was 23%; 24% were born before 1970, 10% during 1970-1979, 21% during 1980-1989, and 17% in 2000 or later.

The most common congenital diseases for the entire group was ventricular septal defect (22%), followed by atrial septal defect (15%), and pulmonary valve abnormality (10%).

Among infants born in 1990-1999, mortality from congenital heart disease was due to cardiac failure in 56%, postoperative complications in 22%, and perioperative complications in 9%. In the 1990-1999 subgroup, survival during follow-up was 99% in patients with mild congenital heart disease, 90% in those with moderate disease, and 59% in patients with a complex abnormality, said Dr. Moons, a health services researcher at Catholic University.

Major Findings: Survival to adulthood has significantly improved for persons born with congenital heart disease, from 82% in those born in the 1970s to 89% in those born in the 1990s.

Data Source: Clinical database of 17,044 patients in the congenital heart disease program at Catholic University, Leuven, Belgium.

Disclosures: Dr. Moons had no financial conflicts of interest to report.

ORLANDO — Infants born with a congenital heart disease during 1990-1999 who underwent care at a tertiary center had an 89% actuarial survival rate to age 18 or older, data on more than 3,800 patients at one Belgium center showed.

That was a significant improvement over 85% survival to adulthood for infants born during 1980-1989 and managed at the same center, and the 82% rate in those born during 1970-1979, Philip Moons, Ph.D., said at the annual scientific sessions of the American Heart Association.

The 89% rate improved on the 85% rate from the 32nd Bethesda Conference in a report based on outcomes of congenital heart disease patients born in the 1980s, Dr. Moon said (J. Am. Coll. Cardiol. 2001;37:1170-5).

Dr. Moons and his associates analyzed survival data from the clinical database of the congenital heart disease program at Catholic University, Leuven, Belgium. It included 17,044 patients born with gross structural abnormalities of the heart or intrathoracic great vessels with actual or potential functional significance. The subset of these patients born during 1990-1999 was 23%; 24% were born before 1970, 10% during 1970-1979, 21% during 1980-1989, and 17% in 2000 or later.

The most common congenital diseases for the entire group was ventricular septal defect (22%), followed by atrial septal defect (15%), and pulmonary valve abnormality (10%).

Among infants born in 1990-1999, mortality from congenital heart disease was due to cardiac failure in 56%, postoperative complications in 22%, and perioperative complications in 9%. In the 1990-1999 subgroup, survival during follow-up was 99% in patients with mild congenital heart disease, 90% in those with moderate disease, and 59% in patients with a complex abnormality, said Dr. Moons, a health services researcher at Catholic University.

Major Finding: At 24 weeks, Patient Global Assessment scores improved in 50% of the 304 heart failure patients receiving intravenous iron and in 28% of the 155 patients on placebo, a statistically significant difference.

Source of Data: FAIR-HF, placebo-controlled phase III study of 459 patients, from 75 sites in 11 countries, randomized to iron or placebo.

Disclosures: The study was sponsored by Vifor Pharma, a Swiss company that markets Ferinject in Europe. Dr. Jessup disclosed that she is a speaker for, or consultant to, Boston Scientific, Medtronic, Ventracor, and ACORN. Dr. Cleland received research support from several drug and cardiac device companies.

ORLANDO — The clinical benefits from intravenous iron in chronic heart failure seen in a placebo-controlled study of 459 patients abruptly made iron repletion a new, plausible treatment for a sizable fraction of heart failure patients.

“This is a new therapeutic concept. When patients [with heart failure] are symptomatic, physicians should think about iron deficiency,” Dr. Stefan D. Anker said at the annual scientific sessions of the American Heart Association. The study results also showed that the boost from iron occurred regardless of whether patients were anemic before starting treatment, a finding that suggests iron helps patients by a mechanism that does not involve hemoglobin.

The study findings “are very intriguing. Iron deficiency hasn't been on our radar screen,” commented Dr. Mariell L. Jessup, professor of medicine and associate chief of clinical affairs in the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia. “I think this is something that people will start to act on quickly. I wouldn't be surprised if some physicians start to say, 'You're iron deficient? Let's give you some iron.' Iron supplements by injection are clearly [already] out there in the nephrology world.”

“Iron deficiency is extremely common in this population if you look for it. Intravenous iron is probably the way to go,” commented Dr. John G.F. Cleland, professor and chairman of cardiology at the University of Hull, England.

Dr. Cleland, who has studied oral iron supplements in heart failure patients, and has found that by that route repletion lags and clinical benefits are lacking, possibly because many heart failure patients have impaired iron absorption in their gut, he said in an interview.

Despite the promising new results, Dr. Anker stressed that the study was not powered to adequately address safety or efficacy end points such as survival and hospitalization. Further study is needed to build up a larger experience with the tested agent, ferric carboxymaltose, in heart failure patients, although Dr. Anker's study included 150 patient-years of treatment with this drug with no hint of excess adverse events aside from an expected, modest increase in gastrointestinal disorders. Dr. Anker also expressed eagerness to test this strategy in patients with diastolic dysfunction: heart failure with preserved left ventricular function.

About 20%–30% of heart failure patients likely have iron deficiency, said Dr. Anker, professor in the Center for Cardiovascular Research at Charité University in Berlin.

The Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial enrolled patients during June 2007–December 2008 at 75 sites in 11 countries. Dr. Anker and his associates screened more than 950 patients to find the 459 who fulfilled the study's criteria for heart failure and serum ferritin level. Eligible patients had either New York Heart Association class III heart failure and a left ventricular ejection fraction of 45% or less, or class II heart failure and an ejection fraction of 40% or less. Their hemoglobin at enrollment could be 95-135 g/L, and so the study included nearly equal numbers of patients with anemia (hemoglobin of 120 g/L or less) and those without (more than 120 g/L). Their average age was 68, and 82% had class III heart failure.

The researchers randomized patients on a two-to-one basis to receive an intravenous, bolus injection of ferric carboxymaltose equivalent to 200 mg iron weekly or placebo. Once iron repletion occurred, after 8 or 12 weeks, the iron dosage scaled back to one injection every 4 weeks.

The study was sponsored by Vifor Pharma, a Swiss company that markets a formulation of ferric carboxymaltose (Ferinject) in Europe but which does not have U.S. approval. Dr. Anker said that he has received fees from Vifor for consulting, lecturing, and serving on the study's executive committee, and he also has received fees from Roche and Amgen.

After 24 weeks, the self-reported Patient Global Assessment was at least moderately improved in 50% of the 304 patients receiving iron and in 28% of the 155 patients on placebo, a statistically significant difference for this primary end point. New York Heart Association heart failure class improved in 47% of the patients on iron and in 30% of the control patients, also a significant difference in the second primary end point. The results appeared in an article published online (N. Engl. J. Med. 2009 Nov. 17 [doi:10.1056/NEJMoa0908355

Dr. Anker said the fast action may relate to his hypothesis to explain how iron supplementation exerts a benefit that is apparently independent of a hemoglobin effect. “Iron is needed for the proper function of mitochondria to generate energy in both the heart and in peripheral muscles,” Dr. Anker said. “I think intravenous iron is a powerful intervention; it's a legal way to do doping.”

During the study, mortality rates were 3% in the iron group and 6% in the control patients, a nonsignificant difference. Hospitalization for any cardiovascular reason occurred in 10% of the iron patients and 20% of the controls, a difference that came close to, but did not reach, statistical significance. Cardiac disorders of any type were significantly more common in the control patients, 50%, than in those on iron, 28%. The most notable adverse event more common in the iron patients was gastrointestinal disorder, in 17% of the iron patients and 7% of the controls, a difference that just missed statistical significance.

Dr. Anker noted that his findings show no suggestion of a safety concern, but he conceded that the current experience is limited and the drug needs testing in more patients. Vifor Pharma is currently discussing what further steps it will take in studying its ferric carboxymaltose formulation in patients with heart failure, said Dr. David R. Ebsworth, Vifor's chief executive officer.

My Take

'The Effect Occurs So Quickly'

This is a remarkable result. I am especially impressed that the separation in the primary end points between the patients receiving iron and those on placebo began to be statistically significant after the first 4 weeks on treatment and then continued to separate further.

The effect occurs so quickly. This is probably the fastest separation we've seen in a clinical trial in heart failure.

Major Finding: At 24 weeks, Patient Global Assessment scores improved in 50% of the 304 heart failure patients receiving intravenous iron and in 28% of the 155 patients on placebo, a statistically significant difference.

Source of Data: FAIR-HF, placebo-controlled phase III study of 459 patients, from 75 sites in 11 countries, randomized to iron or placebo.

Disclosures: The study was sponsored by Vifor Pharma, a Swiss company that markets Ferinject in Europe. Dr. Jessup disclosed that she is a speaker for, or consultant to, Boston Scientific, Medtronic, Ventracor, and ACORN. Dr. Cleland received research support from several drug and cardiac device companies.

ORLANDO — The clinical benefits from intravenous iron in chronic heart failure seen in a placebo-controlled study of 459 patients abruptly made iron repletion a new, plausible treatment for a sizable fraction of heart failure patients.

“This is a new therapeutic concept. When patients [with heart failure] are symptomatic, physicians should think about iron deficiency,” Dr. Stefan D. Anker said at the annual scientific sessions of the American Heart Association. The study results also showed that the boost from iron occurred regardless of whether patients were anemic before starting treatment, a finding that suggests iron helps patients by a mechanism that does not involve hemoglobin.

The study findings “are very intriguing. Iron deficiency hasn't been on our radar screen,” commented Dr. Mariell L. Jessup, professor of medicine and associate chief of clinical affairs in the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia. “I think this is something that people will start to act on quickly. I wouldn't be surprised if some physicians start to say, 'You're iron deficient? Let's give you some iron.' Iron supplements by injection are clearly [already] out there in the nephrology world.”

“Iron deficiency is extremely common in this population if you look for it. Intravenous iron is probably the way to go,” commented Dr. John G.F. Cleland, professor and chairman of cardiology at the University of Hull, England.

Dr. Cleland, who has studied oral iron supplements in heart failure patients, and has found that by that route repletion lags and clinical benefits are lacking, possibly because many heart failure patients have impaired iron absorption in their gut, he said in an interview.

Despite the promising new results, Dr. Anker stressed that the study was not powered to adequately address safety or efficacy end points such as survival and hospitalization. Further study is needed to build up a larger experience with the tested agent, ferric carboxymaltose, in heart failure patients, although Dr. Anker's study included 150 patient-years of treatment with this drug with no hint of excess adverse events aside from an expected, modest increase in gastrointestinal disorders. Dr. Anker also expressed eagerness to test this strategy in patients with diastolic dysfunction: heart failure with preserved left ventricular function.

About 20%–30% of heart failure patients likely have iron deficiency, said Dr. Anker, professor in the Center for Cardiovascular Research at Charité University in Berlin.

The Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial enrolled patients during June 2007–December 2008 at 75 sites in 11 countries. Dr. Anker and his associates screened more than 950 patients to find the 459 who fulfilled the study's criteria for heart failure and serum ferritin level. Eligible patients had either New York Heart Association class III heart failure and a left ventricular ejection fraction of 45% or less, or class II heart failure and an ejection fraction of 40% or less. Their hemoglobin at enrollment could be 95-135 g/L, and so the study included nearly equal numbers of patients with anemia (hemoglobin of 120 g/L or less) and those without (more than 120 g/L). Their average age was 68, and 82% had class III heart failure.

The researchers randomized patients on a two-to-one basis to receive an intravenous, bolus injection of ferric carboxymaltose equivalent to 200 mg iron weekly or placebo. Once iron repletion occurred, after 8 or 12 weeks, the iron dosage scaled back to one injection every 4 weeks.

The study was sponsored by Vifor Pharma, a Swiss company that markets a formulation of ferric carboxymaltose (Ferinject) in Europe but which does not have U.S. approval. Dr. Anker said that he has received fees from Vifor for consulting, lecturing, and serving on the study's executive committee, and he also has received fees from Roche and Amgen.

After 24 weeks, the self-reported Patient Global Assessment was at least moderately improved in 50% of the 304 patients receiving iron and in 28% of the 155 patients on placebo, a statistically significant difference for this primary end point. New York Heart Association heart failure class improved in 47% of the patients on iron and in 30% of the control patients, also a significant difference in the second primary end point. The results appeared in an article published online (N. Engl. J. Med. 2009 Nov. 17 [doi:10.1056/NEJMoa0908355

Dr. Anker said the fast action may relate to his hypothesis to explain how iron supplementation exerts a benefit that is apparently independent of a hemoglobin effect. “Iron is needed for the proper function of mitochondria to generate energy in both the heart and in peripheral muscles,” Dr. Anker said. “I think intravenous iron is a powerful intervention; it's a legal way to do doping.”

During the study, mortality rates were 3% in the iron group and 6% in the control patients, a nonsignificant difference. Hospitalization for any cardiovascular reason occurred in 10% of the iron patients and 20% of the controls, a difference that came close to, but did not reach, statistical significance. Cardiac disorders of any type were significantly more common in the control patients, 50%, than in those on iron, 28%. The most notable adverse event more common in the iron patients was gastrointestinal disorder, in 17% of the iron patients and 7% of the controls, a difference that just missed statistical significance.

Dr. Anker noted that his findings show no suggestion of a safety concern, but he conceded that the current experience is limited and the drug needs testing in more patients. Vifor Pharma is currently discussing what further steps it will take in studying its ferric carboxymaltose formulation in patients with heart failure, said Dr. David R. Ebsworth, Vifor's chief executive officer.

My Take

'The Effect Occurs So Quickly'

This is a remarkable result. I am especially impressed that the separation in the primary end points between the patients receiving iron and those on placebo began to be statistically significant after the first 4 weeks on treatment and then continued to separate further.

The effect occurs so quickly. This is probably the fastest separation we've seen in a clinical trial in heart failure.

Major Finding: At 24 weeks, Patient Global Assessment scores improved in 50% of the 304 heart failure patients receiving intravenous iron and in 28% of the 155 patients on placebo, a statistically significant difference.

Source of Data: FAIR-HF, placebo-controlled phase III study of 459 patients, from 75 sites in 11 countries, randomized to iron or placebo.

Disclosures: The study was sponsored by Vifor Pharma, a Swiss company that markets Ferinject in Europe. Dr. Jessup disclosed that she is a speaker for, or consultant to, Boston Scientific, Medtronic, Ventracor, and ACORN. Dr. Cleland received research support from several drug and cardiac device companies.

ORLANDO — The clinical benefits from intravenous iron in chronic heart failure seen in a placebo-controlled study of 459 patients abruptly made iron repletion a new, plausible treatment for a sizable fraction of heart failure patients.

“This is a new therapeutic concept. When patients [with heart failure] are symptomatic, physicians should think about iron deficiency,” Dr. Stefan D. Anker said at the annual scientific sessions of the American Heart Association. The study results also showed that the boost from iron occurred regardless of whether patients were anemic before starting treatment, a finding that suggests iron helps patients by a mechanism that does not involve hemoglobin.

The study findings “are very intriguing. Iron deficiency hasn't been on our radar screen,” commented Dr. Mariell L. Jessup, professor of medicine and associate chief of clinical affairs in the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia. “I think this is something that people will start to act on quickly. I wouldn't be surprised if some physicians start to say, 'You're iron deficient? Let's give you some iron.' Iron supplements by injection are clearly [already] out there in the nephrology world.”

“Iron deficiency is extremely common in this population if you look for it. Intravenous iron is probably the way to go,” commented Dr. John G.F. Cleland, professor and chairman of cardiology at the University of Hull, England.

Dr. Cleland, who has studied oral iron supplements in heart failure patients, and has found that by that route repletion lags and clinical benefits are lacking, possibly because many heart failure patients have impaired iron absorption in their gut, he said in an interview.

Despite the promising new results, Dr. Anker stressed that the study was not powered to adequately address safety or efficacy end points such as survival and hospitalization. Further study is needed to build up a larger experience with the tested agent, ferric carboxymaltose, in heart failure patients, although Dr. Anker's study included 150 patient-years of treatment with this drug with no hint of excess adverse events aside from an expected, modest increase in gastrointestinal disorders. Dr. Anker also expressed eagerness to test this strategy in patients with diastolic dysfunction: heart failure with preserved left ventricular function.

About 20%–30% of heart failure patients likely have iron deficiency, said Dr. Anker, professor in the Center for Cardiovascular Research at Charité University in Berlin.

The Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial enrolled patients during June 2007–December 2008 at 75 sites in 11 countries. Dr. Anker and his associates screened more than 950 patients to find the 459 who fulfilled the study's criteria for heart failure and serum ferritin level. Eligible patients had either New York Heart Association class III heart failure and a left ventricular ejection fraction of 45% or less, or class II heart failure and an ejection fraction of 40% or less. Their hemoglobin at enrollment could be 95-135 g/L, and so the study included nearly equal numbers of patients with anemia (hemoglobin of 120 g/L or less) and those without (more than 120 g/L). Their average age was 68, and 82% had class III heart failure.

The researchers randomized patients on a two-to-one basis to receive an intravenous, bolus injection of ferric carboxymaltose equivalent to 200 mg iron weekly or placebo. Once iron repletion occurred, after 8 or 12 weeks, the iron dosage scaled back to one injection every 4 weeks.

The study was sponsored by Vifor Pharma, a Swiss company that markets a formulation of ferric carboxymaltose (Ferinject) in Europe but which does not have U.S. approval. Dr. Anker said that he has received fees from Vifor for consulting, lecturing, and serving on the study's executive committee, and he also has received fees from Roche and Amgen.

After 24 weeks, the self-reported Patient Global Assessment was at least moderately improved in 50% of the 304 patients receiving iron and in 28% of the 155 patients on placebo, a statistically significant difference for this primary end point. New York Heart Association heart failure class improved in 47% of the patients on iron and in 30% of the control patients, also a significant difference in the second primary end point. The results appeared in an article published online (N. Engl. J. Med. 2009 Nov. 17 [doi:10.1056/NEJMoa0908355

Dr. Anker said the fast action may relate to his hypothesis to explain how iron supplementation exerts a benefit that is apparently independent of a hemoglobin effect. “Iron is needed for the proper function of mitochondria to generate energy in both the heart and in peripheral muscles,” Dr. Anker said. “I think intravenous iron is a powerful intervention; it's a legal way to do doping.”

During the study, mortality rates were 3% in the iron group and 6% in the control patients, a nonsignificant difference. Hospitalization for any cardiovascular reason occurred in 10% of the iron patients and 20% of the controls, a difference that came close to, but did not reach, statistical significance. Cardiac disorders of any type were significantly more common in the control patients, 50%, than in those on iron, 28%. The most notable adverse event more common in the iron patients was gastrointestinal disorder, in 17% of the iron patients and 7% of the controls, a difference that just missed statistical significance.

Dr. Anker noted that his findings show no suggestion of a safety concern, but he conceded that the current experience is limited and the drug needs testing in more patients. Vifor Pharma is currently discussing what further steps it will take in studying its ferric carboxymaltose formulation in patients with heart failure, said Dr. David R. Ebsworth, Vifor's chief executive officer.

My Take

'The Effect Occurs So Quickly'

This is a remarkable result. I am especially impressed that the separation in the primary end points between the patients receiving iron and those on placebo began to be statistically significant after the first 4 weeks on treatment and then continued to separate further.

The effect occurs so quickly. This is probably the fastest separation we've seen in a clinical trial in heart failure.

Much of the American public has unofficially declared the influenza A(H1N1) pandemic of 2009-2010 over, even though health officials continue to urge Americans to get vaccinated.

The U.S. population spoke with its unrolled sleeves and averted nostrils. That's to say that during January, the period when the H1N1 vaccine was available to all U.S. residents and not officially limited to just those in high-risk groups, the pace of vaccination fell to the relatively low rate of about 9 million people immunized during the month. This was a significant drop compared with an average rate of about 20 million vaccinations per month from October through December, according to survey results and extrapolations made by the Centers for Disease Control and Prevention (CDC).

Interest in the H1N1 vaccine in January ran parallel with the low level of H1N1 infection that month. During the final week of January, the CDC's sentinel system found that 1.9% of physician visits involved influenza, with virtually all identified strains H1N1, compared with a national baseline level “during the off-season” of 2.3%, indicating infection rates were far from epidemic.

The prospects for much more H1N1 vaccine uptake by Americans seem dim, given results from a poll conducted Jan. 20-24 by the Harvard Opinion Research Program of Harvard University's School of Public Health, Boston. A telephone interview survey of more than 1,400 American adults found that 44% said the H1N1 outbreak was “over,” and only 32% had concern that they or someone in their immediate family might get sick from H1N1 during the next several months.

The poll also found that 61% of respondents had not received the H1N1 vaccine and did not intend to get it in the future, with 37% of those polled saying their major reason for shunning the vaccine was that they did not think the H1N1 outbreak to be as serious now as public health officials once thought.

“The skepticism of this group indicates that, going forward, it may be difficult to get more movement in the percentage of adults vaccinated for H1N1,” Robert J. Blendon, Sc.D., professor of health policy and political analysis at Harvard and director of the Opinion Research Program, said in a statement.

“The public aren't dummies. They figured out that despite the exhortations of the CDC to still get vaccinated [against H1N1] because the virus is still out there, at the moment it's a much quieter flu season than usual and so they are not lining up for vaccine,” said Dr. William Schaffner, professor and chairman of the department of preventive medicine at Vanderbilt University in Nashville. “In Tennessee, we have ample supplies of vaccine and few customers right now. The stock is not moving.”

CDC officials maintained their commitment to widespread vaccination of the American public against H1N1. At a media briefing in February, Dr. Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases, warned that “many people believe the outbreak is over, and I think it's too soon for us to have that type of complacency. … My sense is that we are not at all out of the woods, because the [H1N1] virus continues to circulate. The chances of a very large, additional wave are very hard to predict.”

But indications are that the CDC will not meet a receptive public unless a third wave of widespread H1N1 infection does indeed occur before the end of the flu season this spring.

Statistics show the H1N1 vaccine never caught on in the United States. The approximately 70 million Americans who got the vaccine through the end of January—23% of the population according to CDC numbers—contrasts with the 32% of Americans who received the seasonal 2009-2010 flu vaccine through mid-November 2009, according to a survey by the RAND Corp. For the 2008-2009 season, 38% of American adults had received the seasonal flu vaccine as of March 2009, according to RAND.

Experts cite poor timing in the H1N1 vaccine's availability last fall, confusion about who was to get the vaccine based on its limited early supply, and concerns about the vaccine's safety.

“The vaccine was too little, too late in the public's mind,” said Dr. Gregory A. Poland, professor of medicine and director of the vaccine research group at the Mayo Clinic, Rochester, Minn.

“Vaccine availability peaked just as the second wave of the pandemic diminished.” The public “waited and waited for [the vaccine], and when it become available they stopped hearing reports of cases.” Another important factor was the “underlying distrust and suspicion about vaccines, with many Americans believing the vaccine was too rushed, untested, and not safe.”

The striking difference in H1N1 vaccine uptake, compared with the reception the seasonal flu vaccine received in September through November, isn't surprising because “people looked at the H1N1 vaccine differently,” Dr. Poland said in an interview.

“People are familiar with the seasonal vaccine and presumably more comfortable with its safety; drugstores and supermarkets heavily promoted [seasonal] flu shots; and most important, in contrast to H1N1, there was seasonal vaccine available to meet demand at the time vaccination was being heavily promoted. The public heeded the call to be vaccinated early,” said Katherine M. Harris, Ph.D., a senior economist at RAND Corp. and lead researcher on RAND's flu vaccine surveys. “Three times as many people were vaccinated against seasonal flu in September compared with the same time last year.”

Dr. Georges C. Benjamin, executive director of the American Public Health Association, agreed. “Seasonal vaccine was available in an environment when people were concerned about the flu. Public health officials were effective at promoting the need to get seasonal vaccine. The diminishing risk of high mortality and morbidity from H1N1 in the broader population reinforced the belief that the [H1N1] vaccine was not essential. The failure of a third wave to occur to date has also reinforced this belief.”

Dr. Benjamin also cited the public's safety concerns about the “new” H1N1 vaccine, and confusion about the number of vaccinations needed for protection.

Dr. Poland highlighted the tiered approach that targeted the earliest available H1N1 vaccine exclusively to high-risk people as another factor that dissipated momentum of the vaccination effort last fall.

“It caused delay, and as a result we'll have tens of millions of H1N1 vaccines go to waste.”

The major underlying problem appears to have been a mismatch between vaccine supply and demand, which meant missing the key vaccination window as the second wave of H1N1 infection built and peaked last fall.

“The single biggest problem is that we did not have enough vaccine early enough,” Dr. Schaffner said. “The bulk of the vaccine began to arrive between the [Thanksgiving and Christmas] holidays, and there was a sense by then that H1N1 had peaked.”

Because the vaccine strain of the H1N1 virus grew more slowly than expected, “the output of vaccine was not optimal,” Dr. Benjamin said. “This argues for current efforts the scientific community is undertaking to use newer methods to make the vaccine.”

Disclosures: Because the federal government fully funded H1N1 vaccine production, the sources in this article have no relevant disclosures, except for Dr. Schuchat, who is a government employee.

'We have ample supplies of vaccine and few customers right now. The stock is not moving.'

Source: DR. SCHAFFNER

Much of the American public has unofficially declared the influenza A(H1N1) pandemic of 2009-2010 over, even though health officials continue to urge Americans to get vaccinated.

The U.S. population spoke with its unrolled sleeves and averted nostrils. That's to say that during January, the period when the H1N1 vaccine was available to all U.S. residents and not officially limited to just those in high-risk groups, the pace of vaccination fell to the relatively low rate of about 9 million people immunized during the month. This was a significant drop compared with an average rate of about 20 million vaccinations per month from October through December, according to survey results and extrapolations made by the Centers for Disease Control and Prevention (CDC).

Interest in the H1N1 vaccine in January ran parallel with the low level of H1N1 infection that month. During the final week of January, the CDC's sentinel system found that 1.9% of physician visits involved influenza, with virtually all identified strains H1N1, compared with a national baseline level “during the off-season” of 2.3%, indicating infection rates were far from epidemic.

The prospects for much more H1N1 vaccine uptake by Americans seem dim, given results from a poll conducted Jan. 20-24 by the Harvard Opinion Research Program of Harvard University's School of Public Health, Boston. A telephone interview survey of more than 1,400 American adults found that 44% said the H1N1 outbreak was “over,” and only 32% had concern that they or someone in their immediate family might get sick from H1N1 during the next several months.

The poll also found that 61% of respondents had not received the H1N1 vaccine and did not intend to get it in the future, with 37% of those polled saying their major reason for shunning the vaccine was that they did not think the H1N1 outbreak to be as serious now as public health officials once thought.

“The skepticism of this group indicates that, going forward, it may be difficult to get more movement in the percentage of adults vaccinated for H1N1,” Robert J. Blendon, Sc.D., professor of health policy and political analysis at Harvard and director of the Opinion Research Program, said in a statement.

“The public aren't dummies. They figured out that despite the exhortations of the CDC to still get vaccinated [against H1N1] because the virus is still out there, at the moment it's a much quieter flu season than usual and so they are not lining up for vaccine,” said Dr. William Schaffner, professor and chairman of the department of preventive medicine at Vanderbilt University in Nashville. “In Tennessee, we have ample supplies of vaccine and few customers right now. The stock is not moving.”

CDC officials maintained their commitment to widespread vaccination of the American public against H1N1. At a media briefing in February, Dr. Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases, warned that “many people believe the outbreak is over, and I think it's too soon for us to have that type of complacency. … My sense is that we are not at all out of the woods, because the [H1N1] virus continues to circulate. The chances of a very large, additional wave are very hard to predict.”

But indications are that the CDC will not meet a receptive public unless a third wave of widespread H1N1 infection does indeed occur before the end of the flu season this spring.

Statistics show the H1N1 vaccine never caught on in the United States. The approximately 70 million Americans who got the vaccine through the end of January—23% of the population according to CDC numbers—contrasts with the 32% of Americans who received the seasonal 2009-2010 flu vaccine through mid-November 2009, according to a survey by the RAND Corp. For the 2008-2009 season, 38% of American adults had received the seasonal flu vaccine as of March 2009, according to RAND.

Experts cite poor timing in the H1N1 vaccine's availability last fall, confusion about who was to get the vaccine based on its limited early supply, and concerns about the vaccine's safety.

“The vaccine was too little, too late in the public's mind,” said Dr. Gregory A. Poland, professor of medicine and director of the vaccine research group at the Mayo Clinic, Rochester, Minn.

“Vaccine availability peaked just as the second wave of the pandemic diminished.” The public “waited and waited for [the vaccine], and when it become available they stopped hearing reports of cases.” Another important factor was the “underlying distrust and suspicion about vaccines, with many Americans believing the vaccine was too rushed, untested, and not safe.”

The striking difference in H1N1 vaccine uptake, compared with the reception the seasonal flu vaccine received in September through November, isn't surprising because “people looked at the H1N1 vaccine differently,” Dr. Poland said in an interview.

“People are familiar with the seasonal vaccine and presumably more comfortable with its safety; drugstores and supermarkets heavily promoted [seasonal] flu shots; and most important, in contrast to H1N1, there was seasonal vaccine available to meet demand at the time vaccination was being heavily promoted. The public heeded the call to be vaccinated early,” said Katherine M. Harris, Ph.D., a senior economist at RAND Corp. and lead researcher on RAND's flu vaccine surveys. “Three times as many people were vaccinated against seasonal flu in September compared with the same time last year.”

Dr. Georges C. Benjamin, executive director of the American Public Health Association, agreed. “Seasonal vaccine was available in an environment when people were concerned about the flu. Public health officials were effective at promoting the need to get seasonal vaccine. The diminishing risk of high mortality and morbidity from H1N1 in the broader population reinforced the belief that the [H1N1] vaccine was not essential. The failure of a third wave to occur to date has also reinforced this belief.”

Dr. Benjamin also cited the public's safety concerns about the “new” H1N1 vaccine, and confusion about the number of vaccinations needed for protection.

Dr. Poland highlighted the tiered approach that targeted the earliest available H1N1 vaccine exclusively to high-risk people as another factor that dissipated momentum of the vaccination effort last fall.

“It caused delay, and as a result we'll have tens of millions of H1N1 vaccines go to waste.”

The major underlying problem appears to have been a mismatch between vaccine supply and demand, which meant missing the key vaccination window as the second wave of H1N1 infection built and peaked last fall.

“The single biggest problem is that we did not have enough vaccine early enough,” Dr. Schaffner said. “The bulk of the vaccine began to arrive between the [Thanksgiving and Christmas] holidays, and there was a sense by then that H1N1 had peaked.”

Because the vaccine strain of the H1N1 virus grew more slowly than expected, “the output of vaccine was not optimal,” Dr. Benjamin said. “This argues for current efforts the scientific community is undertaking to use newer methods to make the vaccine.”

Disclosures: Because the federal government fully funded H1N1 vaccine production, the sources in this article have no relevant disclosures, except for Dr. Schuchat, who is a government employee.

'We have ample supplies of vaccine and few customers right now. The stock is not moving.'

Source: DR. SCHAFFNER

Much of the American public has unofficially declared the influenza A(H1N1) pandemic of 2009-2010 over, even though health officials continue to urge Americans to get vaccinated.

The U.S. population spoke with its unrolled sleeves and averted nostrils. That's to say that during January, the period when the H1N1 vaccine was available to all U.S. residents and not officially limited to just those in high-risk groups, the pace of vaccination fell to the relatively low rate of about 9 million people immunized during the month. This was a significant drop compared with an average rate of about 20 million vaccinations per month from October through December, according to survey results and extrapolations made by the Centers for Disease Control and Prevention (CDC).

Interest in the H1N1 vaccine in January ran parallel with the low level of H1N1 infection that month. During the final week of January, the CDC's sentinel system found that 1.9% of physician visits involved influenza, with virtually all identified strains H1N1, compared with a national baseline level “during the off-season” of 2.3%, indicating infection rates were far from epidemic.

The prospects for much more H1N1 vaccine uptake by Americans seem dim, given results from a poll conducted Jan. 20-24 by the Harvard Opinion Research Program of Harvard University's School of Public Health, Boston. A telephone interview survey of more than 1,400 American adults found that 44% said the H1N1 outbreak was “over,” and only 32% had concern that they or someone in their immediate family might get sick from H1N1 during the next several months.

The poll also found that 61% of respondents had not received the H1N1 vaccine and did not intend to get it in the future, with 37% of those polled saying their major reason for shunning the vaccine was that they did not think the H1N1 outbreak to be as serious now as public health officials once thought.

“The skepticism of this group indicates that, going forward, it may be difficult to get more movement in the percentage of adults vaccinated for H1N1,” Robert J. Blendon, Sc.D., professor of health policy and political analysis at Harvard and director of the Opinion Research Program, said in a statement.

“The public aren't dummies. They figured out that despite the exhortations of the CDC to still get vaccinated [against H1N1] because the virus is still out there, at the moment it's a much quieter flu season than usual and so they are not lining up for vaccine,” said Dr. William Schaffner, professor and chairman of the department of preventive medicine at Vanderbilt University in Nashville. “In Tennessee, we have ample supplies of vaccine and few customers right now. The stock is not moving.”

CDC officials maintained their commitment to widespread vaccination of the American public against H1N1. At a media briefing in February, Dr. Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases, warned that “many people believe the outbreak is over, and I think it's too soon for us to have that type of complacency. … My sense is that we are not at all out of the woods, because the [H1N1] virus continues to circulate. The chances of a very large, additional wave are very hard to predict.”

But indications are that the CDC will not meet a receptive public unless a third wave of widespread H1N1 infection does indeed occur before the end of the flu season this spring.

Statistics show the H1N1 vaccine never caught on in the United States. The approximately 70 million Americans who got the vaccine through the end of January—23% of the population according to CDC numbers—contrasts with the 32% of Americans who received the seasonal 2009-2010 flu vaccine through mid-November 2009, according to a survey by the RAND Corp. For the 2008-2009 season, 38% of American adults had received the seasonal flu vaccine as of March 2009, according to RAND.

Experts cite poor timing in the H1N1 vaccine's availability last fall, confusion about who was to get the vaccine based on its limited early supply, and concerns about the vaccine's safety.

“The vaccine was too little, too late in the public's mind,” said Dr. Gregory A. Poland, professor of medicine and director of the vaccine research group at the Mayo Clinic, Rochester, Minn.

“Vaccine availability peaked just as the second wave of the pandemic diminished.” The public “waited and waited for [the vaccine], and when it become available they stopped hearing reports of cases.” Another important factor was the “underlying distrust and suspicion about vaccines, with many Americans believing the vaccine was too rushed, untested, and not safe.”

The striking difference in H1N1 vaccine uptake, compared with the reception the seasonal flu vaccine received in September through November, isn't surprising because “people looked at the H1N1 vaccine differently,” Dr. Poland said in an interview.

“People are familiar with the seasonal vaccine and presumably more comfortable with its safety; drugstores and supermarkets heavily promoted [seasonal] flu shots; and most important, in contrast to H1N1, there was seasonal vaccine available to meet demand at the time vaccination was being heavily promoted. The public heeded the call to be vaccinated early,” said Katherine M. Harris, Ph.D., a senior economist at RAND Corp. and lead researcher on RAND's flu vaccine surveys. “Three times as many people were vaccinated against seasonal flu in September compared with the same time last year.”

Dr. Georges C. Benjamin, executive director of the American Public Health Association, agreed. “Seasonal vaccine was available in an environment when people were concerned about the flu. Public health officials were effective at promoting the need to get seasonal vaccine. The diminishing risk of high mortality and morbidity from H1N1 in the broader population reinforced the belief that the [H1N1] vaccine was not essential. The failure of a third wave to occur to date has also reinforced this belief.”

Dr. Benjamin also cited the public's safety concerns about the “new” H1N1 vaccine, and confusion about the number of vaccinations needed for protection.

Dr. Poland highlighted the tiered approach that targeted the earliest available H1N1 vaccine exclusively to high-risk people as another factor that dissipated momentum of the vaccination effort last fall.

“It caused delay, and as a result we'll have tens of millions of H1N1 vaccines go to waste.”

The major underlying problem appears to have been a mismatch between vaccine supply and demand, which meant missing the key vaccination window as the second wave of H1N1 infection built and peaked last fall.

“The single biggest problem is that we did not have enough vaccine early enough,” Dr. Schaffner said. “The bulk of the vaccine began to arrive between the [Thanksgiving and Christmas] holidays, and there was a sense by then that H1N1 had peaked.”

Because the vaccine strain of the H1N1 virus grew more slowly than expected, “the output of vaccine was not optimal,” Dr. Benjamin said. “This argues for current efforts the scientific community is undertaking to use newer methods to make the vaccine.”

Disclosures: Because the federal government fully funded H1N1 vaccine production, the sources in this article have no relevant disclosures, except for Dr. Schuchat, who is a government employee.

'We have ample supplies of vaccine and few customers right now. The stock is not moving.'

Source: DR. SCHAFFNER

Now that more than one injectable formulation of botulinum toxin is on the market, the competition may help drive down prices. 

Aside from potential price differences, little seems to distinguish the two injectable formulations of botulinum toxin type A on the market, Botox (Allergan) and Dysport (Medicis), Dr. Mark G. Rubin explained at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

"As of January 2010, I have injected over 700 patients with Dysport, all of whom have had Botox previously. In the vast majority of patients, they were unable to tell the difference," said Dr. Rubin, a dermatologist in private practice in Beverly Hills, Calif.

Price competition among various botulinum toxin type A brands will likely intensify when additional formulations, PurTox (Mentor) and Xeomin (Merz), receive expected Food and Drug Administration approvals.

These brands differ by parameters that include complexing proteins, dose equivalency, and need for refrigeration, but available data suggest few meaningful differences exist except for storage temperature. Both Botox and Dysport require refrigerated storage, while Xeomin and PurTox are stable when stored at temperatures up to 25º C, Dr. Rubin noted.

Perhaps the most hyped difference among botulinum toxin type A formulations is spread or diffusion following injection, a property also known as "field of effect." The evidence indicates little difference in the diffusion rates of Botox and Dysport, according to Dr. Rubin.

The active molecule in botulinum toxin type A is identical in all formulations. The difference is the complexing proteins that wrap around the active molecule. Data reported at the Toxins 2008 meeting in Baveno, Italy showed that, at physiological pH, the active molecule dissociates from complexing protein within 1 minute, after which diffusion should be the same for all formulations.

This interpretation received further support from data that showed the onset of action, efficacy, and duration of effect of Botox and Xeomin were nearly identical (Neurology 2005;64:1949-51; J. Neural Transm. 2006;113:303-12).

Additional results from other studies have also supported the notion that Botox, Dysport, and Xeomin all act in similar ways, he noted. Moreover, trials done for the FDA for treatment of blepharospasm and cervical dystonia showed similar adverse effect profiles for Botox and Xeomin, suggesting similar diffusion rates.

The only other area in which some of these products differ is in dosing. Xeomin and PurTox appear roughly similar in dosing to Botox, with 1 unit of each being about equivalent to 1 unit of Botox. Dysport, though, has different dosing: 2.5 units of Dysport generally have the same effect as 1 unit of Botox.

Dysport and Botox also have shown similar efficacy and adverse effect profiles in clinical studies, according to Dr. Rubin. In effects on frown lines, Botox has been found to have 84% efficacy, compared with 90% for Dysport. Median duration of response has been found to be 90 days for Botox and 117 days for Dysport. The incidence of headaches is reported to be 15% with Botox and 11% with Dysport, and the rate of blepharoptosis is 5% with Botox and less than 2% with Dysport, he reported.

^{Photo Courtesy Dr. Mark G. Rubin}

Dr. Rubin disclosed being a consultant to Medicis, the company that markets Dysport, and to Revance Therapeutics, a company developing a topical formulation of botulinum toxin. SDEF and this news organization are owned by Elsevier.

Now that more than one injectable formulation of botulinum toxin is on the market, the competition may help drive down prices. 

Aside from potential price differences, little seems to distinguish the two injectable formulations of botulinum toxin type A on the market, Botox (Allergan) and Dysport (Medicis), Dr. Mark G. Rubin explained at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

"As of January 2010, I have injected over 700 patients with Dysport, all of whom have had Botox previously. In the vast majority of patients, they were unable to tell the difference," said Dr. Rubin, a dermatologist in private practice in Beverly Hills, Calif.

Price competition among various botulinum toxin type A brands will likely intensify when additional formulations, PurTox (Mentor) and Xeomin (Merz), receive expected Food and Drug Administration approvals.

These brands differ by parameters that include complexing proteins, dose equivalency, and need for refrigeration, but available data suggest few meaningful differences exist except for storage temperature. Both Botox and Dysport require refrigerated storage, while Xeomin and PurTox are stable when stored at temperatures up to 25º C, Dr. Rubin noted.

Perhaps the most hyped difference among botulinum toxin type A formulations is spread or diffusion following injection, a property also known as "field of effect." The evidence indicates little difference in the diffusion rates of Botox and Dysport, according to Dr. Rubin.

The active molecule in botulinum toxin type A is identical in all formulations. The difference is the complexing proteins that wrap around the active molecule. Data reported at the Toxins 2008 meeting in Baveno, Italy showed that, at physiological pH, the active molecule dissociates from complexing protein within 1 minute, after which diffusion should be the same for all formulations.

This interpretation received further support from data that showed the onset of action, efficacy, and duration of effect of Botox and Xeomin were nearly identical (Neurology 2005;64:1949-51; J. Neural Transm. 2006;113:303-12).

Additional results from other studies have also supported the notion that Botox, Dysport, and Xeomin all act in similar ways, he noted. Moreover, trials done for the FDA for treatment of blepharospasm and cervical dystonia showed similar adverse effect profiles for Botox and Xeomin, suggesting similar diffusion rates.

The only other area in which some of these products differ is in dosing. Xeomin and PurTox appear roughly similar in dosing to Botox, with 1 unit of each being about equivalent to 1 unit of Botox. Dysport, though, has different dosing: 2.5 units of Dysport generally have the same effect as 1 unit of Botox.

Dysport and Botox also have shown similar efficacy and adverse effect profiles in clinical studies, according to Dr. Rubin. In effects on frown lines, Botox has been found to have 84% efficacy, compared with 90% for Dysport. Median duration of response has been found to be 90 days for Botox and 117 days for Dysport. The incidence of headaches is reported to be 15% with Botox and 11% with Dysport, and the rate of blepharoptosis is 5% with Botox and less than 2% with Dysport, he reported.

^{Photo Courtesy Dr. Mark G. Rubin}

Dr. Rubin disclosed being a consultant to Medicis, the company that markets Dysport, and to Revance Therapeutics, a company developing a topical formulation of botulinum toxin. SDEF and this news organization are owned by Elsevier.

Now that more than one injectable formulation of botulinum toxin is on the market, the competition may help drive down prices. 

Aside from potential price differences, little seems to distinguish the two injectable formulations of botulinum toxin type A on the market, Botox (Allergan) and Dysport (Medicis), Dr. Mark G. Rubin explained at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

"As of January 2010, I have injected over 700 patients with Dysport, all of whom have had Botox previously. In the vast majority of patients, they were unable to tell the difference," said Dr. Rubin, a dermatologist in private practice in Beverly Hills, Calif.

Price competition among various botulinum toxin type A brands will likely intensify when additional formulations, PurTox (Mentor) and Xeomin (Merz), receive expected Food and Drug Administration approvals.

These brands differ by parameters that include complexing proteins, dose equivalency, and need for refrigeration, but available data suggest few meaningful differences exist except for storage temperature. Both Botox and Dysport require refrigerated storage, while Xeomin and PurTox are stable when stored at temperatures up to 25º C, Dr. Rubin noted.

Perhaps the most hyped difference among botulinum toxin type A formulations is spread or diffusion following injection, a property also known as "field of effect." The evidence indicates little difference in the diffusion rates of Botox and Dysport, according to Dr. Rubin.

The active molecule in botulinum toxin type A is identical in all formulations. The difference is the complexing proteins that wrap around the active molecule. Data reported at the Toxins 2008 meeting in Baveno, Italy showed that, at physiological pH, the active molecule dissociates from complexing protein within 1 minute, after which diffusion should be the same for all formulations.

This interpretation received further support from data that showed the onset of action, efficacy, and duration of effect of Botox and Xeomin were nearly identical (Neurology 2005;64:1949-51; J. Neural Transm. 2006;113:303-12).

Additional results from other studies have also supported the notion that Botox, Dysport, and Xeomin all act in similar ways, he noted. Moreover, trials done for the FDA for treatment of blepharospasm and cervical dystonia showed similar adverse effect profiles for Botox and Xeomin, suggesting similar diffusion rates.

The only other area in which some of these products differ is in dosing. Xeomin and PurTox appear roughly similar in dosing to Botox, with 1 unit of each being about equivalent to 1 unit of Botox. Dysport, though, has different dosing: 2.5 units of Dysport generally have the same effect as 1 unit of Botox.

Dysport and Botox also have shown similar efficacy and adverse effect profiles in clinical studies, according to Dr. Rubin. In effects on frown lines, Botox has been found to have 84% efficacy, compared with 90% for Dysport. Median duration of response has been found to be 90 days for Botox and 117 days for Dysport. The incidence of headaches is reported to be 15% with Botox and 11% with Dysport, and the rate of blepharoptosis is 5% with Botox and less than 2% with Dysport, he reported.

^{Photo Courtesy Dr. Mark G. Rubin}

Dr. Rubin disclosed being a consultant to Medicis, the company that markets Dysport, and to Revance Therapeutics, a company developing a topical formulation of botulinum toxin. SDEF and this news organization are owned by Elsevier.

New criteria for diagnosing rheumatoid arthritis should lead to earlier diagnoses, easier insurance coverage for treatment, and improved patient outcomes, agreed many rheumatologists. The new criteria are also likely to be adopted fairly quickly, experts added.

“It's a paradigm shift: Prevent disease or significantly abrogate it if rheumatoid arthritis is caught early. If you wait for the 1987 criteria to be fulfilled, patients will have established disease. Our goal is to identify and treat patients as early as possible,” said Dr. Clifton O. Bingham III, associate director of the Johns Hopkins Arthritis Center in Baltimore and a member of the panel that came up with the new RA criteria.

A panel of 22 rheumatologists formed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) worked for 3 years to devise new RA diagnostic criteria to replace the existing RA classification criteria that were released by the ACR in 1987 (Arthritis Rheum. 1988;31:315-24). An initial public report on the new diagnostic criteria occurred last October at the annual meeting of the ACR in Philadelphia. (See box.) A peer-reviewed, written version of the criteria, as well as reports on the multistage process that led to their creation, should appear later this year in a trio of articles in the journals Arthritis & Rheumatism and Annals of the Rheumatic Diseases, said Dr. Gillian A. Hawker, chief of medicine at Women's College Hospital in Toronto and a project leader.

“This will lead to earlier, definitive assessment and treatment of patients with RA. A major weakness of the previous classification criteria is that they included a bad outcome [and] erosions, and required more extensive disease. We want to treat patients before erosions occur,” said Dr. Eric L. Matteson, professor and chairman of rheumatology at the Mayo Clinic in Rochester, Minn.

“These criteria should help clinicians diagnose patients at an earlier stage, and possibly lead to earlier treatment as well, thereby improving outcomes. They may help qualify patients for therapy at an earlier stage of their disease,” said Dr. Arthur F. Kavanaugh, professor of medicine at the University of California, San Diego.

A major way in which the new criteria enable earlier diagnosis is by setting a lower threshold for the number of involved joints, noted Dr. Michael E. Weinblatt, professor of medicine at Harvard Medical School and associate director of the center for arthritis and joint diseases at Brigham and Women's Hospital, both in Boston. “A lot of times patients don't seek care or don't get referred because only a couple of joints are involved.” The new criteria make it clear that “a couple of joints could be RA.”

These criteria “will allow for earlier diagnosis, but there is a great deal of clinical judgment [involved], and I've certainly diagnosed RA in many patients who did not fulfill the [1987] ACR criteria,” said Dr. Daniel Furst, professor of medicine at the University of California, Los Angeles. “What this does is codify and validate the fact that we make diagnoses earlier” than the old classification criteria allowed. Now primary care physicians “will feel comfortable making an earlier diagnosis,” he said.

Earlier diagnosis was a major goal of the panel that came up with the new diagnostic criteria, based on an “increasing concern that we were missing patients with aggressive, erosive disease,” said Dr. Philip J. Mease, a panel member and a rheumatologist at Swedish Hospital Medical Center in Seattle. “I'm not sure that the criteria will identify more patients, but they will more precisely identify patients who'll have an aggressive course. The hope is that if you start treatment [of these patients] sooner, you may prevent disease progression.”

Experts were split on how confident they were that earlier diagnosis and treatment would lead to better outcomes, although that's what they generally expect.

“We hope it leads to better outcomes. That's the underlying assumption,” said Dr. Furst.

“Earlier treatment of RA means better outcomes, including less irreversible damage,” said Dr. Matteson.

Dr. Mease said that some evidence already exists for improved outcomes from early treatment. He cited results from studies such as TICORA (Tight Control for Rheumatoid Arthritis) (Lancet 2004;364:263-9), BeSt (Behandel-Strategieën) (Arthritis Rheum. 2005:52:3381-90), and CAMERA (Computer-Assisted Management of Early Rheumatoid Arthritis) (Ann. Rheum. Dis. 2007;66:1443-9). Results from all three studies showed that aggressive treatment early in RA led to better outcomes, with lower joint counts, better function, and more significant inhibition of radiologic damage, Dr. Mease said in an interview.

The new criteria should also ease insurance-coverage problems, said some experts. Currently, some insurers ask whether the patient fulfills the 1987 criteria for RA, “and if you answer truthfully, some patients [with early RA] may not fulfill the criteria.” The 2009 criteria “may allow earlier access to medications. This will make it easier to document RA,” said Dr. Bingham.

The number of involved joints has been a diagnostic feature that has held up insurance coverage for some patients, with insurers insisting that patients meet the 1987 standard of at least six involved joints, Dr. Weinblatt said. Dr. Furst and Dr. Matteson also cited experiences with denied insurance coverage, something they anticipate will become a thing of the past, more or less, with the new criteria.

“The first thing insurers ask in prior authorization forms is whether a patient meets the criteria for RA,” Dr. Weinblatt noted. This slowed the use of disease-modifying antirheumatic drugs in some patients. The new criteria will eliminate this barrier in many cases, he said.

Although all the experts who were interviewed agreed that the new criteria accurately reflected current thinking on what constitutes RA, a few envisioned certain situations that could cause problems. One concern involved mixing apples and oranges: Could results from RA patients in prior treatment studies always be appropriately applied to patients whose disease is defined by the new criteria? Dr. Furst asked. Similarly, he wondered whether drug toxicity profiles that were worked out in prior cohorts of RA patients would match the toxicities faced by newly defined RA patients.

Dr. Mease said he was concerned about a group of patients who are sick but fall short of the diagnostic criteria. These are the patients who present with fewer than 10 involved medium or large joints, low titers of rheumatoid factor and anti–citrullinated protein antibody, and a very high level of C-reactive protein, a constellation showing that the patient “clearly has an inflammatory process,” yet one that would tally a diagnostic score of 4-5 points (depending on symptom duration), which is less than the 6 points needed for a definitive RA diagnosis. Despite such concerns, Dr. Furst noted that the 2009 criteria had higher specificity and sensitivity than did the 1987 criteria. Also, new serologic and genomic tests that will likely emerge in the next several years will further refine diagnoses and will be incorporated into the scoring formula, Dr. Mease said.

“I think it will improve the outcome of our patients, and so it's a very good thing,” said Dr. Furst. The new criteria will become widely adopted because “all of us who talk about it will insist on it. But I bet it will take longer than we'd like.”

Dr. Bingham and Dr. Mease participated on the panel that developed the criteria; this work was sponsored by the ACR and EULAR.

The rheumatologists who were interviewed said that because the new criteria do not deal directly with treatment, they did not have relevant disclosures on the topic.

The new EULAR/ACR criteria aim to diagnose rheumatoid arthritis before formation of bone erosions, as shown here.

Source ©J. Cavallini/Custom Medical Stock Photo

The New Criteria in Brief

Patients are definitively diagnosed with RA if they score 6 or more points according to these criteria:

Joint Involvement

▸ 1 medium-large joint (0 points)

▸ 2-10 medium-large joints (1 point)

▸ 1-3 small joints (2 points)

▸ 4-10 small joints (3 points)

▸ More than 10 small joints (5 points)

Serology

▸ Not positive for either rheumatoid factor or anti–citrullinated protein antibody (0 points)

▸ At least one of these two tests are positive at low titer, defined as more than the upper limit of normal but not higher than three times the upper limit of normal (2 points)

▸ At least one test is positive at high titer, defined as more than three times the upper limit of normal (3 points)

Duration of synovitis

▸ Lasting fewer than 6 weeks (0 points)

▸ Lasting 6 weeks or longer (1 point)

Acute phase reactants

▸ Neither C-reactive protein nor erythrocyte sedimentation rate is abnormal (0 points)

▸ Abnormal CRP or abnormal ESR (1 point)

Note: Patients receive the highest point level they fulfill within each domain. For example, a patient with five small joints involved and four large joints involved scores 3 points, according to the criteria.

Note: Based on presentation by Dr. Hawker at the annual meeting of the American College of Rheumatology, October, 2009.

New criteria for diagnosing rheumatoid arthritis should lead to earlier diagnoses, easier insurance coverage for treatment, and improved patient outcomes, agreed many rheumatologists. The new criteria are also likely to be adopted fairly quickly, experts added.

“It's a paradigm shift: Prevent disease or significantly abrogate it if rheumatoid arthritis is caught early. If you wait for the 1987 criteria to be fulfilled, patients will have established disease. Our goal is to identify and treat patients as early as possible,” said Dr. Clifton O. Bingham III, associate director of the Johns Hopkins Arthritis Center in Baltimore and a member of the panel that came up with the new RA criteria.

A panel of 22 rheumatologists formed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) worked for 3 years to devise new RA diagnostic criteria to replace the existing RA classification criteria that were released by the ACR in 1987 (Arthritis Rheum. 1988;31:315-24). An initial public report on the new diagnostic criteria occurred last October at the annual meeting of the ACR in Philadelphia. (See box.) A peer-reviewed, written version of the criteria, as well as reports on the multistage process that led to their creation, should appear later this year in a trio of articles in the journals Arthritis & Rheumatism and Annals of the Rheumatic Diseases, said Dr. Gillian A. Hawker, chief of medicine at Women's College Hospital in Toronto and a project leader.

“This will lead to earlier, definitive assessment and treatment of patients with RA. A major weakness of the previous classification criteria is that they included a bad outcome [and] erosions, and required more extensive disease. We want to treat patients before erosions occur,” said Dr. Eric L. Matteson, professor and chairman of rheumatology at the Mayo Clinic in Rochester, Minn.

“These criteria should help clinicians diagnose patients at an earlier stage, and possibly lead to earlier treatment as well, thereby improving outcomes. They may help qualify patients for therapy at an earlier stage of their disease,” said Dr. Arthur F. Kavanaugh, professor of medicine at the University of California, San Diego.

A major way in which the new criteria enable earlier diagnosis is by setting a lower threshold for the number of involved joints, noted Dr. Michael E. Weinblatt, professor of medicine at Harvard Medical School and associate director of the center for arthritis and joint diseases at Brigham and Women's Hospital, both in Boston. “A lot of times patients don't seek care or don't get referred because only a couple of joints are involved.” The new criteria make it clear that “a couple of joints could be RA.”

These criteria “will allow for earlier diagnosis, but there is a great deal of clinical judgment [involved], and I've certainly diagnosed RA in many patients who did not fulfill the [1987] ACR criteria,” said Dr. Daniel Furst, professor of medicine at the University of California, Los Angeles. “What this does is codify and validate the fact that we make diagnoses earlier” than the old classification criteria allowed. Now primary care physicians “will feel comfortable making an earlier diagnosis,” he said.

Earlier diagnosis was a major goal of the panel that came up with the new diagnostic criteria, based on an “increasing concern that we were missing patients with aggressive, erosive disease,” said Dr. Philip J. Mease, a panel member and a rheumatologist at Swedish Hospital Medical Center in Seattle. “I'm not sure that the criteria will identify more patients, but they will more precisely identify patients who'll have an aggressive course. The hope is that if you start treatment [of these patients] sooner, you may prevent disease progression.”

Experts were split on how confident they were that earlier diagnosis and treatment would lead to better outcomes, although that's what they generally expect.

“We hope it leads to better outcomes. That's the underlying assumption,” said Dr. Furst.

“Earlier treatment of RA means better outcomes, including less irreversible damage,” said Dr. Matteson.

Dr. Mease said that some evidence already exists for improved outcomes from early treatment. He cited results from studies such as TICORA (Tight Control for Rheumatoid Arthritis) (Lancet 2004;364:263-9), BeSt (Behandel-Strategieën) (Arthritis Rheum. 2005:52:3381-90), and CAMERA (Computer-Assisted Management of Early Rheumatoid Arthritis) (Ann. Rheum. Dis. 2007;66:1443-9). Results from all three studies showed that aggressive treatment early in RA led to better outcomes, with lower joint counts, better function, and more significant inhibition of radiologic damage, Dr. Mease said in an interview.

The new criteria should also ease insurance-coverage problems, said some experts. Currently, some insurers ask whether the patient fulfills the 1987 criteria for RA, “and if you answer truthfully, some patients [with early RA] may not fulfill the criteria.” The 2009 criteria “may allow earlier access to medications. This will make it easier to document RA,” said Dr. Bingham.

The number of involved joints has been a diagnostic feature that has held up insurance coverage for some patients, with insurers insisting that patients meet the 1987 standard of at least six involved joints, Dr. Weinblatt said. Dr. Furst and Dr. Matteson also cited experiences with denied insurance coverage, something they anticipate will become a thing of the past, more or less, with the new criteria.

“The first thing insurers ask in prior authorization forms is whether a patient meets the criteria for RA,” Dr. Weinblatt noted. This slowed the use of disease-modifying antirheumatic drugs in some patients. The new criteria will eliminate this barrier in many cases, he said.

Although all the experts who were interviewed agreed that the new criteria accurately reflected current thinking on what constitutes RA, a few envisioned certain situations that could cause problems. One concern involved mixing apples and oranges: Could results from RA patients in prior treatment studies always be appropriately applied to patients whose disease is defined by the new criteria? Dr. Furst asked. Similarly, he wondered whether drug toxicity profiles that were worked out in prior cohorts of RA patients would match the toxicities faced by newly defined RA patients.

Dr. Mease said he was concerned about a group of patients who are sick but fall short of the diagnostic criteria. These are the patients who present with fewer than 10 involved medium or large joints, low titers of rheumatoid factor and anti–citrullinated protein antibody, and a very high level of C-reactive protein, a constellation showing that the patient “clearly has an inflammatory process,” yet one that would tally a diagnostic score of 4-5 points (depending on symptom duration), which is less than the 6 points needed for a definitive RA diagnosis. Despite such concerns, Dr. Furst noted that the 2009 criteria had higher specificity and sensitivity than did the 1987 criteria. Also, new serologic and genomic tests that will likely emerge in the next several years will further refine diagnoses and will be incorporated into the scoring formula, Dr. Mease said.

“I think it will improve the outcome of our patients, and so it's a very good thing,” said Dr. Furst. The new criteria will become widely adopted because “all of us who talk about it will insist on it. But I bet it will take longer than we'd like.”

Dr. Bingham and Dr. Mease participated on the panel that developed the criteria; this work was sponsored by the ACR and EULAR.

The rheumatologists who were interviewed said that because the new criteria do not deal directly with treatment, they did not have relevant disclosures on the topic.

The new EULAR/ACR criteria aim to diagnose rheumatoid arthritis before formation of bone erosions, as shown here.

Source ©J. Cavallini/Custom Medical Stock Photo

The New Criteria in Brief

Patients are definitively diagnosed with RA if they score 6 or more points according to these criteria:

Joint Involvement

▸ 1 medium-large joint (0 points)

▸ 2-10 medium-large joints (1 point)

▸ 1-3 small joints (2 points)

▸ 4-10 small joints (3 points)

▸ More than 10 small joints (5 points)

Serology

▸ Not positive for either rheumatoid factor or anti–citrullinated protein antibody (0 points)

▸ At least one of these two tests are positive at low titer, defined as more than the upper limit of normal but not higher than three times the upper limit of normal (2 points)

▸ At least one test is positive at high titer, defined as more than three times the upper limit of normal (3 points)

Duration of synovitis

▸ Lasting fewer than 6 weeks (0 points)

▸ Lasting 6 weeks or longer (1 point)

Acute phase reactants

▸ Neither C-reactive protein nor erythrocyte sedimentation rate is abnormal (0 points)

▸ Abnormal CRP or abnormal ESR (1 point)

Note: Patients receive the highest point level they fulfill within each domain. For example, a patient with five small joints involved and four large joints involved scores 3 points, according to the criteria.

Note: Based on presentation by Dr. Hawker at the annual meeting of the American College of Rheumatology, October, 2009.

New criteria for diagnosing rheumatoid arthritis should lead to earlier diagnoses, easier insurance coverage for treatment, and improved patient outcomes, agreed many rheumatologists. The new criteria are also likely to be adopted fairly quickly, experts added.

“It's a paradigm shift: Prevent disease or significantly abrogate it if rheumatoid arthritis is caught early. If you wait for the 1987 criteria to be fulfilled, patients will have established disease. Our goal is to identify and treat patients as early as possible,” said Dr. Clifton O. Bingham III, associate director of the Johns Hopkins Arthritis Center in Baltimore and a member of the panel that came up with the new RA criteria.

A panel of 22 rheumatologists formed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) worked for 3 years to devise new RA diagnostic criteria to replace the existing RA classification criteria that were released by the ACR in 1987 (Arthritis Rheum. 1988;31:315-24). An initial public report on the new diagnostic criteria occurred last October at the annual meeting of the ACR in Philadelphia. (See box.) A peer-reviewed, written version of the criteria, as well as reports on the multistage process that led to their creation, should appear later this year in a trio of articles in the journals Arthritis & Rheumatism and Annals of the Rheumatic Diseases, said Dr. Gillian A. Hawker, chief of medicine at Women's College Hospital in Toronto and a project leader.

“This will lead to earlier, definitive assessment and treatment of patients with RA. A major weakness of the previous classification criteria is that they included a bad outcome [and] erosions, and required more extensive disease. We want to treat patients before erosions occur,” said Dr. Eric L. Matteson, professor and chairman of rheumatology at the Mayo Clinic in Rochester, Minn.

“These criteria should help clinicians diagnose patients at an earlier stage, and possibly lead to earlier treatment as well, thereby improving outcomes. They may help qualify patients for therapy at an earlier stage of their disease,” said Dr. Arthur F. Kavanaugh, professor of medicine at the University of California, San Diego.

A major way in which the new criteria enable earlier diagnosis is by setting a lower threshold for the number of involved joints, noted Dr. Michael E. Weinblatt, professor of medicine at Harvard Medical School and associate director of the center for arthritis and joint diseases at Brigham and Women's Hospital, both in Boston. “A lot of times patients don't seek care or don't get referred because only a couple of joints are involved.” The new criteria make it clear that “a couple of joints could be RA.”

These criteria “will allow for earlier diagnosis, but there is a great deal of clinical judgment [involved], and I've certainly diagnosed RA in many patients who did not fulfill the [1987] ACR criteria,” said Dr. Daniel Furst, professor of medicine at the University of California, Los Angeles. “What this does is codify and validate the fact that we make diagnoses earlier” than the old classification criteria allowed. Now primary care physicians “will feel comfortable making an earlier diagnosis,” he said.

Earlier diagnosis was a major goal of the panel that came up with the new diagnostic criteria, based on an “increasing concern that we were missing patients with aggressive, erosive disease,” said Dr. Philip J. Mease, a panel member and a rheumatologist at Swedish Hospital Medical Center in Seattle. “I'm not sure that the criteria will identify more patients, but they will more precisely identify patients who'll have an aggressive course. The hope is that if you start treatment [of these patients] sooner, you may prevent disease progression.”

Experts were split on how confident they were that earlier diagnosis and treatment would lead to better outcomes, although that's what they generally expect.

“We hope it leads to better outcomes. That's the underlying assumption,” said Dr. Furst.

“Earlier treatment of RA means better outcomes, including less irreversible damage,” said Dr. Matteson.

Dr. Mease said that some evidence already exists for improved outcomes from early treatment. He cited results from studies such as TICORA (Tight Control for Rheumatoid Arthritis) (Lancet 2004;364:263-9), BeSt (Behandel-Strategieën) (Arthritis Rheum. 2005:52:3381-90), and CAMERA (Computer-Assisted Management of Early Rheumatoid Arthritis) (Ann. Rheum. Dis. 2007;66:1443-9). Results from all three studies showed that aggressive treatment early in RA led to better outcomes, with lower joint counts, better function, and more significant inhibition of radiologic damage, Dr. Mease said in an interview.

The new criteria should also ease insurance-coverage problems, said some experts. Currently, some insurers ask whether the patient fulfills the 1987 criteria for RA, “and if you answer truthfully, some patients [with early RA] may not fulfill the criteria.” The 2009 criteria “may allow earlier access to medications. This will make it easier to document RA,” said Dr. Bingham.

The number of involved joints has been a diagnostic feature that has held up insurance coverage for some patients, with insurers insisting that patients meet the 1987 standard of at least six involved joints, Dr. Weinblatt said. Dr. Furst and Dr. Matteson also cited experiences with denied insurance coverage, something they anticipate will become a thing of the past, more or less, with the new criteria.

“The first thing insurers ask in prior authorization forms is whether a patient meets the criteria for RA,” Dr. Weinblatt noted. This slowed the use of disease-modifying antirheumatic drugs in some patients. The new criteria will eliminate this barrier in many cases, he said.

Although all the experts who were interviewed agreed that the new criteria accurately reflected current thinking on what constitutes RA, a few envisioned certain situations that could cause problems. One concern involved mixing apples and oranges: Could results from RA patients in prior treatment studies always be appropriately applied to patients whose disease is defined by the new criteria? Dr. Furst asked. Similarly, he wondered whether drug toxicity profiles that were worked out in prior cohorts of RA patients would match the toxicities faced by newly defined RA patients.

Dr. Mease said he was concerned about a group of patients who are sick but fall short of the diagnostic criteria. These are the patients who present with fewer than 10 involved medium or large joints, low titers of rheumatoid factor and anti–citrullinated protein antibody, and a very high level of C-reactive protein, a constellation showing that the patient “clearly has an inflammatory process,” yet one that would tally a diagnostic score of 4-5 points (depending on symptom duration), which is less than the 6 points needed for a definitive RA diagnosis. Despite such concerns, Dr. Furst noted that the 2009 criteria had higher specificity and sensitivity than did the 1987 criteria. Also, new serologic and genomic tests that will likely emerge in the next several years will further refine diagnoses and will be incorporated into the scoring formula, Dr. Mease said.

“I think it will improve the outcome of our patients, and so it's a very good thing,” said Dr. Furst. The new criteria will become widely adopted because “all of us who talk about it will insist on it. But I bet it will take longer than we'd like.”

Dr. Bingham and Dr. Mease participated on the panel that developed the criteria; this work was sponsored by the ACR and EULAR.

The rheumatologists who were interviewed said that because the new criteria do not deal directly with treatment, they did not have relevant disclosures on the topic.

The new EULAR/ACR criteria aim to diagnose rheumatoid arthritis before formation of bone erosions, as shown here.

Source ©J. Cavallini/Custom Medical Stock Photo

The New Criteria in Brief

Patients are definitively diagnosed with RA if they score 6 or more points according to these criteria:

Joint Involvement

▸ 1 medium-large joint (0 points)

▸ 2-10 medium-large joints (1 point)

▸ 1-3 small joints (2 points)

▸ 4-10 small joints (3 points)

▸ More than 10 small joints (5 points)

Serology

▸ Not positive for either rheumatoid factor or anti–citrullinated protein antibody (0 points)

▸ At least one of these two tests are positive at low titer, defined as more than the upper limit of normal but not higher than three times the upper limit of normal (2 points)

▸ At least one test is positive at high titer, defined as more than three times the upper limit of normal (3 points)

Duration of synovitis

▸ Lasting fewer than 6 weeks (0 points)

▸ Lasting 6 weeks or longer (1 point)

Acute phase reactants

▸ Neither C-reactive protein nor erythrocyte sedimentation rate is abnormal (0 points)

▸ Abnormal CRP or abnormal ESR (1 point)

Note: Patients receive the highest point level they fulfill within each domain. For example, a patient with five small joints involved and four large joints involved scores 3 points, according to the criteria.

Note: Based on presentation by Dr. Hawker at the annual meeting of the American College of Rheumatology, October, 2009.

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, and now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to patients aged 13-17 years safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. “The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied early, before BMI gets too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said.

“Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

In one analysis of 61 adolescent gastric bypass patients, the average percentage of lost BMI was about 37% across all weight categories, and two-thirds of the variance in BMI 1 year after surgery was attributable to the variance in baseline BMI (J. Pediatr. 2010;156:103-8).

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Last year, a surgeon from that group, Dr. Thomas H. Inge of Cincinnati Children's Hospital, worked with a different group of collaborators to write revised criteria, which set their threshold BMI at 35 or 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869-76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's.

He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” he said in an interview.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastro-esophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues.

“The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

Disclosures: Dr. Inge has received research funding from Ethicon Inc. Dr. Pratt has served as a consultant to Covidien. Dr. Nadler received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

'The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities.'

Source DR. PRATT

'It's a new concept to think of surgery as preventive medicine, but it is preventive.'

Source DR. HOLTERMAN

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, and now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to patients aged 13-17 years safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. “The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied early, before BMI gets too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said.

“Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

In one analysis of 61 adolescent gastric bypass patients, the average percentage of lost BMI was about 37% across all weight categories, and two-thirds of the variance in BMI 1 year after surgery was attributable to the variance in baseline BMI (J. Pediatr. 2010;156:103-8).

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Last year, a surgeon from that group, Dr. Thomas H. Inge of Cincinnati Children's Hospital, worked with a different group of collaborators to write revised criteria, which set their threshold BMI at 35 or 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869-76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's.

He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” he said in an interview.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastro-esophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues.

“The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

Disclosures: Dr. Inge has received research funding from Ethicon Inc. Dr. Pratt has served as a consultant to Covidien. Dr. Nadler received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

'The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities.'

Source DR. PRATT

'It's a new concept to think of surgery as preventive medicine, but it is preventive.'

Source DR. HOLTERMAN

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, and now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to patients aged 13-17 years safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. “The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied early, before BMI gets too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said.

“Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

In one analysis of 61 adolescent gastric bypass patients, the average percentage of lost BMI was about 37% across all weight categories, and two-thirds of the variance in BMI 1 year after surgery was attributable to the variance in baseline BMI (J. Pediatr. 2010;156:103-8).

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Last year, a surgeon from that group, Dr. Thomas H. Inge of Cincinnati Children's Hospital, worked with a different group of collaborators to write revised criteria, which set their threshold BMI at 35 or 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869-76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's.

He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” he said in an interview.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastro-esophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues.

“The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

Disclosures: Dr. Inge has received research funding from Ethicon Inc. Dr. Pratt has served as a consultant to Covidien. Dr. Nadler received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

'The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities.'

Source DR. PRATT

'It's a new concept to think of surgery as preventive medicine, but it is preventive.'

Source DR. HOLTERMAN

ORLANDO — Development of new-onset atrial fibrillation soon after cardiac surgery presents a sharply increased risk for also having atrial fibrillation several years later, as well as significantly worse long-term survival, according to a study of more than 500 patients.

“Aggressive preventive measures should be applied, especially for patients undergoing cardiac surgery who are at high risk for postoperative atrial fibrillation,” Dr. Rowlens M. Melduni said at the annual scientific sessions of the American Heart Association.

“Atrial fibrillation is a symptom, not a disease. It's a marker of underlying cardiovascular disease,” said Dr. Melduni, a cardiologist at the Mayo Clinic in Rochester, Minn.

To examine the long-term consequences of early AF after cardiac surgery, Dr. Melduni and his associates studied 534 patients from Olmsted County, Minn. The patients, who had no history of AF prior to surgery, underwent coronary bypass surgery, valve surgery, or both between January 2000 and December 2005. Their average age was 66 years, and 70% were men. During the first 30 days after surgery, 37% developed AF, an incidence rate consistent with several prior reports.

During follow-up, which lasted an average of 4 years, the cumulative occurrence of late AF—defined as episodes occurring more than 30 days following surgery—was 51% in patients who had early AF after cardiac surgery and 13% in patients who did not, a significant difference. The average time from surgery to the appearance of late AF was 2.5 years.

In a multivariate analysis, independent risk factors for developing late AF were having early AF after cardiac surgery, which boosted the risk fivefold; undergoing combined bypass and valve surgery, which raised the risk nearly threefold; and developing postoperative renal dysfunction with a serum creatinine level greater than 2 mg/dL, which doubled the risk. This model adjusted for other potential variables such as age, gender, and treatment with a beta-blocker at hospital discharge.

During follow-up, the cumulative survival rate was 60% in patients who had early AF and 78% in those without early AF, a significant difference.

The duration of early AF was also an independent determinant of long-term risk. Patients whose early AF persisted for 3 or more days had twice the risk for late AF as did those with early AF lasting less than 3 days, Dr. Melduni said.

Results from a second study presented by Dr. Melduni in a poster at the meeting documented that patients who developed early postoperative AF often had high left ventricular end diastolic pressure.

Disclosures: None.

Vitals

Source Elsevier Global Medical Newswww.nejm.org

ORLANDO — Development of new-onset atrial fibrillation soon after cardiac surgery presents a sharply increased risk for also having atrial fibrillation several years later, as well as significantly worse long-term survival, according to a study of more than 500 patients.

“Aggressive preventive measures should be applied, especially for patients undergoing cardiac surgery who are at high risk for postoperative atrial fibrillation,” Dr. Rowlens M. Melduni said at the annual scientific sessions of the American Heart Association.

“Atrial fibrillation is a symptom, not a disease. It's a marker of underlying cardiovascular disease,” said Dr. Melduni, a cardiologist at the Mayo Clinic in Rochester, Minn.

To examine the long-term consequences of early AF after cardiac surgery, Dr. Melduni and his associates studied 534 patients from Olmsted County, Minn. The patients, who had no history of AF prior to surgery, underwent coronary bypass surgery, valve surgery, or both between January 2000 and December 2005. Their average age was 66 years, and 70% were men. During the first 30 days after surgery, 37% developed AF, an incidence rate consistent with several prior reports.

During follow-up, which lasted an average of 4 years, the cumulative occurrence of late AF—defined as episodes occurring more than 30 days following surgery—was 51% in patients who had early AF after cardiac surgery and 13% in patients who did not, a significant difference. The average time from surgery to the appearance of late AF was 2.5 years.

In a multivariate analysis, independent risk factors for developing late AF were having early AF after cardiac surgery, which boosted the risk fivefold; undergoing combined bypass and valve surgery, which raised the risk nearly threefold; and developing postoperative renal dysfunction with a serum creatinine level greater than 2 mg/dL, which doubled the risk. This model adjusted for other potential variables such as age, gender, and treatment with a beta-blocker at hospital discharge.

During follow-up, the cumulative survival rate was 60% in patients who had early AF and 78% in those without early AF, a significant difference.

The duration of early AF was also an independent determinant of long-term risk. Patients whose early AF persisted for 3 or more days had twice the risk for late AF as did those with early AF lasting less than 3 days, Dr. Melduni said.

Results from a second study presented by Dr. Melduni in a poster at the meeting documented that patients who developed early postoperative AF often had high left ventricular end diastolic pressure.

Disclosures: None.

Vitals

Source Elsevier Global Medical Newswww.nejm.org

ORLANDO — Development of new-onset atrial fibrillation soon after cardiac surgery presents a sharply increased risk for also having atrial fibrillation several years later, as well as significantly worse long-term survival, according to a study of more than 500 patients.

“Aggressive preventive measures should be applied, especially for patients undergoing cardiac surgery who are at high risk for postoperative atrial fibrillation,” Dr. Rowlens M. Melduni said at the annual scientific sessions of the American Heart Association.

“Atrial fibrillation is a symptom, not a disease. It's a marker of underlying cardiovascular disease,” said Dr. Melduni, a cardiologist at the Mayo Clinic in Rochester, Minn.

To examine the long-term consequences of early AF after cardiac surgery, Dr. Melduni and his associates studied 534 patients from Olmsted County, Minn. The patients, who had no history of AF prior to surgery, underwent coronary bypass surgery, valve surgery, or both between January 2000 and December 2005. Their average age was 66 years, and 70% were men. During the first 30 days after surgery, 37% developed AF, an incidence rate consistent with several prior reports.

During follow-up, which lasted an average of 4 years, the cumulative occurrence of late AF—defined as episodes occurring more than 30 days following surgery—was 51% in patients who had early AF after cardiac surgery and 13% in patients who did not, a significant difference. The average time from surgery to the appearance of late AF was 2.5 years.

In a multivariate analysis, independent risk factors for developing late AF were having early AF after cardiac surgery, which boosted the risk fivefold; undergoing combined bypass and valve surgery, which raised the risk nearly threefold; and developing postoperative renal dysfunction with a serum creatinine level greater than 2 mg/dL, which doubled the risk. This model adjusted for other potential variables such as age, gender, and treatment with a beta-blocker at hospital discharge.

During follow-up, the cumulative survival rate was 60% in patients who had early AF and 78% in those without early AF, a significant difference.

The duration of early AF was also an independent determinant of long-term risk. Patients whose early AF persisted for 3 or more days had twice the risk for late AF as did those with early AF lasting less than 3 days, Dr. Melduni said.

Results from a second study presented by Dr. Melduni in a poster at the meeting documented that patients who developed early postoperative AF often had high left ventricular end diastolic pressure.

Disclosures: None.

Vitals

Source Elsevier Global Medical Newswww.nejm.org

FORT LAUDERDALE, FLA. — Later this year, coronary bypass patients will start steering their surgeon choices by the stars. A one-to-three star rating system for cardiac surgeons developed by the Society for Thoracic Surgeons will appear on a Consumer Reports Web site, probably beginning in June.

In a bold step toward getting outcomes-based rankings of surgeons out to the public in a user-friendly format, the society teamed with the Consumers Union, publisher of Consumer Reports, to disseminate rankings of U.S. programs offering coronary artery bypass grafting (CABG). The data come from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, which gathers surgery and outcomes data from about 90% of practicing U.S. cardiac surgeons. The ranking will be posted at www.consumerreports.org/health

The STS leadership is soliciting formal consent from each of its practicing U.S. members; the process requires a physician's consent to place ratings for the practice on the site. The STS leadership first introduced the concept to its members last September, and since then has steadily promoted the idea. As of late January, almost 100 practices had signed releases, nearly 10% of the roughly 1,000 U.S. cardiac surgery practices that perform CABG. The society's immediate goal is to have at least 300 consents on file by mid-March to ensure a robust start. Once that foundation exists, additional participation will likely follow, said Dr. Frederick L. Grover, chairman of the STS council on quality, research, and patient safety and a recent former president of the group.

Each participating practice will receive star ratings in five categories: overall bypass surgery performance, patient survival, avoidance of complications, the extent to which the CABG program follows recommended surgical practice, and the extent to which recommended medications are used. Performance of each practice in these categories undergoes risk adjustment and assessment as a ratio of observed relative to expected performance. Performance is then ranked relative to all other practices. Grading will be scaled so that most practices fall into the middle range and receive two stars, while high-level performers will get three stars and the bottom tier receives one star, said Dr. Grover, professor and chairman of surgery at the University of Colorado, Denver.

The STS began contemplating public release of its data this way about a year ago, and contacted Consumers Union to flesh out a strategy. The effort shifted into a higher gear last summer when the STS leadership heard from other consumer groups that were planning their own release of CABG outcomes ratings based on administrative claims data, a source that the STS considers much less reliable than its own database. Those contacts prompted the society to speed development and the timing of the roll-out of its own project, Dr. Glover said in an interview.

In addition to giving the public information it likely wants, a second goal is to further spur surgeons who lag behind the field to improve. “If a program is at one star, hopefully it won't be for more than 1 year. The whole idea is to raise the bar for everyone,” he said.

“We think it's in the best interests of patients and our members,” Dr. Grover said. “It has risk, no doubt about it. Our members are obviously taking chances” by having the relative performance of their surgical practice and outcomes so openly displayed. “It will be interesting to see if it changes referral patterns.”

The society's bottom line is that “the public has the right to know how we're doing,” Dr. Grover added.

FORT LAUDERDALE, FLA. — Later this year, coronary bypass patients will start steering their surgeon choices by the stars. A one-to-three star rating system for cardiac surgeons developed by the Society for Thoracic Surgeons will appear on a Consumer Reports Web site, probably beginning in June.

In a bold step toward getting outcomes-based rankings of surgeons out to the public in a user-friendly format, the society teamed with the Consumers Union, publisher of Consumer Reports, to disseminate rankings of U.S. programs offering coronary artery bypass grafting (CABG). The data come from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, which gathers surgery and outcomes data from about 90% of practicing U.S. cardiac surgeons. The ranking will be posted at www.consumerreports.org/health

The STS leadership is soliciting formal consent from each of its practicing U.S. members; the process requires a physician's consent to place ratings for the practice on the site. The STS leadership first introduced the concept to its members last September, and since then has steadily promoted the idea. As of late January, almost 100 practices had signed releases, nearly 10% of the roughly 1,000 U.S. cardiac surgery practices that perform CABG. The society's immediate goal is to have at least 300 consents on file by mid-March to ensure a robust start. Once that foundation exists, additional participation will likely follow, said Dr. Frederick L. Grover, chairman of the STS council on quality, research, and patient safety and a recent former president of the group.

Each participating practice will receive star ratings in five categories: overall bypass surgery performance, patient survival, avoidance of complications, the extent to which the CABG program follows recommended surgical practice, and the extent to which recommended medications are used. Performance of each practice in these categories undergoes risk adjustment and assessment as a ratio of observed relative to expected performance. Performance is then ranked relative to all other practices. Grading will be scaled so that most practices fall into the middle range and receive two stars, while high-level performers will get three stars and the bottom tier receives one star, said Dr. Grover, professor and chairman of surgery at the University of Colorado, Denver.

The STS began contemplating public release of its data this way about a year ago, and contacted Consumers Union to flesh out a strategy. The effort shifted into a higher gear last summer when the STS leadership heard from other consumer groups that were planning their own release of CABG outcomes ratings based on administrative claims data, a source that the STS considers much less reliable than its own database. Those contacts prompted the society to speed development and the timing of the roll-out of its own project, Dr. Glover said in an interview.

In addition to giving the public information it likely wants, a second goal is to further spur surgeons who lag behind the field to improve. “If a program is at one star, hopefully it won't be for more than 1 year. The whole idea is to raise the bar for everyone,” he said.

“We think it's in the best interests of patients and our members,” Dr. Grover said. “It has risk, no doubt about it. Our members are obviously taking chances” by having the relative performance of their surgical practice and outcomes so openly displayed. “It will be interesting to see if it changes referral patterns.”

The society's bottom line is that “the public has the right to know how we're doing,” Dr. Grover added.

FORT LAUDERDALE, FLA. — Later this year, coronary bypass patients will start steering their surgeon choices by the stars. A one-to-three star rating system for cardiac surgeons developed by the Society for Thoracic Surgeons will appear on a Consumer Reports Web site, probably beginning in June.

In a bold step toward getting outcomes-based rankings of surgeons out to the public in a user-friendly format, the society teamed with the Consumers Union, publisher of Consumer Reports, to disseminate rankings of U.S. programs offering coronary artery bypass grafting (CABG). The data come from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, which gathers surgery and outcomes data from about 90% of practicing U.S. cardiac surgeons. The ranking will be posted at www.consumerreports.org/health

The STS leadership is soliciting formal consent from each of its practicing U.S. members; the process requires a physician's consent to place ratings for the practice on the site. The STS leadership first introduced the concept to its members last September, and since then has steadily promoted the idea. As of late January, almost 100 practices had signed releases, nearly 10% of the roughly 1,000 U.S. cardiac surgery practices that perform CABG. The society's immediate goal is to have at least 300 consents on file by mid-March to ensure a robust start. Once that foundation exists, additional participation will likely follow, said Dr. Frederick L. Grover, chairman of the STS council on quality, research, and patient safety and a recent former president of the group.

Each participating practice will receive star ratings in five categories: overall bypass surgery performance, patient survival, avoidance of complications, the extent to which the CABG program follows recommended surgical practice, and the extent to which recommended medications are used. Performance of each practice in these categories undergoes risk adjustment and assessment as a ratio of observed relative to expected performance. Performance is then ranked relative to all other practices. Grading will be scaled so that most practices fall into the middle range and receive two stars, while high-level performers will get three stars and the bottom tier receives one star, said Dr. Grover, professor and chairman of surgery at the University of Colorado, Denver.

The STS began contemplating public release of its data this way about a year ago, and contacted Consumers Union to flesh out a strategy. The effort shifted into a higher gear last summer when the STS leadership heard from other consumer groups that were planning their own release of CABG outcomes ratings based on administrative claims data, a source that the STS considers much less reliable than its own database. Those contacts prompted the society to speed development and the timing of the roll-out of its own project, Dr. Glover said in an interview.

In addition to giving the public information it likely wants, a second goal is to further spur surgeons who lag behind the field to improve. “If a program is at one star, hopefully it won't be for more than 1 year. The whole idea is to raise the bar for everyone,” he said.

“We think it's in the best interests of patients and our members,” Dr. Grover said. “It has risk, no doubt about it. Our members are obviously taking chances” by having the relative performance of their surgical practice and outcomes so openly displayed. “It will be interesting to see if it changes referral patterns.”

The society's bottom line is that “the public has the right to know how we're doing,” Dr. Grover added.

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, say some surgeons, while other surgeons had already applied the looser criteria for several years. Now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to adolescents (usually defined as patients aged 13-17 years) safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. 'The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied relatively early, before BMI grows too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said. “Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

A series of 61 patients, with an average age of 17, underwent gastric bypass surgery (Roux-en-Y) at Cincinnati Children's Hospital Medical Center between August 2002 and January 2007. Researchers divided the group into three subsets based on their BMI at the time of surgery: 23 had a BMI of 40-54.9 kg/m

Ten of the patients had reached a BMI out of the obese range, less than 30 kg/m

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869-76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's. He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” Dr. Inge said in an interview. Similarly, “in teens, sleep apnea appears to resolve completely” something that usually does not occur in adults. “We tell parents [of obese teenagers] that the obesity will only get worse, and we have tried and true ways to try to reverse” the comorbidities.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastroesophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues. “The most important reason to operate on obese adolescents is not to decrease their weight, but rather to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

A similar interest in early intervention in adolescents exists among surgeons whose focus is gastric banding, which along with gastric sleeves are the surgical alternatives to bypass. Unlike the surgeons who perform gastric bypass surgery, those who do banding have consistently used adult criteria for surgical intervention in adolescent patients. The main limitation of banding has been that as of early 2010 neither of the band devices marketed in the United States for adults had received Food and Drug Administration approval for use in adolescents.

A few years ago, bariatric surgeons at New York University, Rush University, and elsewhere received FDA permission to perform gastric banding on adolescents on an investigational, off-label basis using adult entry criteria. Dr. Nadler, who was with the NYU program at the time, said that he and other surgeons who performed banding never saw a need to be more conservative in their patient-selection criteria than in adults because they viewed banding as less risky than bypass.

“Banding is less invasive and complications are lower and not as serious as with bypass,” he said.

“Gastric bypass is considered more invasive than banding,” agreed Dr. Holterman. Banding is reversible, and it also results in more gradual weight loss since it relies entirely on restricting gastric capacity rather than also on reducing absorption like bypass does, she noted. Dr. Holterman said she prefers an approach that tries banding first, reserving bypass as a later option if needed.

Regardless of which surgical approach is best, now that the field has arrived at a consensus that adolescent surgery is appropriate for patients with BMIs as low as 35 kg/m

Dr. Holterman said that she thinks starting a study of this approach is now reasonable.

The National Institutes of Health established the adult criteria in 1991, and they have not been revised since, Dr. Nadler noted. “I think the operation is safe enough that you can broaden the application. The adult criteria are expanding, and perhaps the adolescent criteria will expand, too.”

Disclosures: Dr. Inge has received research funding from Ethicon Inc., a company that markets a gastric banding device. Dr. Pratt has served as a consultant to Covidien, a company that works with Allergan Inc. to market a gastric banding device. Dr. Nadler has received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

Diabetes, sleep apnea, and nonalcoholic steatohepatitis are 'reversible' with bariatric surgery in adolescents.

Source DR. PRATT

The surgery 'is preventive in the sense that patients have more severe comorbidities if you wait.'

Source DR. HOLTERMAN

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, say some surgeons, while other surgeons had already applied the looser criteria for several years. Now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to adolescents (usually defined as patients aged 13-17 years) safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. 'The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied relatively early, before BMI grows too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said. “Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

A series of 61 patients, with an average age of 17, underwent gastric bypass surgery (Roux-en-Y) at Cincinnati Children's Hospital Medical Center between August 2002 and January 2007. Researchers divided the group into three subsets based on their BMI at the time of surgery: 23 had a BMI of 40-54.9 kg/m

Ten of the patients had reached a BMI out of the obese range, less than 30 kg/m

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869-76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's. He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” Dr. Inge said in an interview. Similarly, “in teens, sleep apnea appears to resolve completely” something that usually does not occur in adults. “We tell parents [of obese teenagers] that the obesity will only get worse, and we have tried and true ways to try to reverse” the comorbidities.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastroesophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues. “The most important reason to operate on obese adolescents is not to decrease their weight, but rather to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

A similar interest in early intervention in adolescents exists among surgeons whose focus is gastric banding, which along with gastric sleeves are the surgical alternatives to bypass. Unlike the surgeons who perform gastric bypass surgery, those who do banding have consistently used adult criteria for surgical intervention in adolescent patients. The main limitation of banding has been that as of early 2010 neither of the band devices marketed in the United States for adults had received Food and Drug Administration approval for use in adolescents.

A few years ago, bariatric surgeons at New York University, Rush University, and elsewhere received FDA permission to perform gastric banding on adolescents on an investigational, off-label basis using adult entry criteria. Dr. Nadler, who was with the NYU program at the time, said that he and other surgeons who performed banding never saw a need to be more conservative in their patient-selection criteria than in adults because they viewed banding as less risky than bypass.

“Banding is less invasive and complications are lower and not as serious as with bypass,” he said.

“Gastric bypass is considered more invasive than banding,” agreed Dr. Holterman. Banding is reversible, and it also results in more gradual weight loss since it relies entirely on restricting gastric capacity rather than also on reducing absorption like bypass does, she noted. Dr. Holterman said she prefers an approach that tries banding first, reserving bypass as a later option if needed.

Regardless of which surgical approach is best, now that the field has arrived at a consensus that adolescent surgery is appropriate for patients with BMIs as low as 35 kg/m

Dr. Holterman said that she thinks starting a study of this approach is now reasonable.

The National Institutes of Health established the adult criteria in 1991, and they have not been revised since, Dr. Nadler noted. “I think the operation is safe enough that you can broaden the application. The adult criteria are expanding, and perhaps the adolescent criteria will expand, too.”

Disclosures: Dr. Inge has received research funding from Ethicon Inc., a company that markets a gastric banding device. Dr. Pratt has served as a consultant to Covidien, a company that works with Allergan Inc. to market a gastric banding device. Dr. Nadler has received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

Diabetes, sleep apnea, and nonalcoholic steatohepatitis are 'reversible' with bariatric surgery in adolescents.

Source DR. PRATT

The surgery 'is preventive in the sense that patients have more severe comorbidities if you wait.'

Source DR. HOLTERMAN

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, say some surgeons, while other surgeons had already applied the looser criteria for several years. Now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to adolescents (usually defined as patients aged 13-17 years) safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. 'The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied relatively early, before BMI grows too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said. “Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

A series of 61 patients, with an average age of 17, underwent gastric bypass surgery (Roux-en-Y) at Cincinnati Children's Hospital Medical Center between August 2002 and January 2007. Researchers divided the group into three subsets based on their BMI at the time of surgery: 23 had a BMI of 40-54.9 kg/m

Ten of the patients had reached a BMI out of the obese range, less than 30 kg/m

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869-76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's. He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” Dr. Inge said in an interview. Similarly, “in teens, sleep apnea appears to resolve completely” something that usually does not occur in adults. “We tell parents [of obese teenagers] that the obesity will only get worse, and we have tried and true ways to try to reverse” the comorbidities.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastroesophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues. “The most important reason to operate on obese adolescents is not to decrease their weight, but rather to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

A similar interest in early intervention in adolescents exists among surgeons whose focus is gastric banding, which along with gastric sleeves are the surgical alternatives to bypass. Unlike the surgeons who perform gastric bypass surgery, those who do banding have consistently used adult criteria for surgical intervention in adolescent patients. The main limitation of banding has been that as of early 2010 neither of the band devices marketed in the United States for adults had received Food and Drug Administration approval for use in adolescents.

A few years ago, bariatric surgeons at New York University, Rush University, and elsewhere received FDA permission to perform gastric banding on adolescents on an investigational, off-label basis using adult entry criteria. Dr. Nadler, who was with the NYU program at the time, said that he and other surgeons who performed banding never saw a need to be more conservative in their patient-selection criteria than in adults because they viewed banding as less risky than bypass.

“Banding is less invasive and complications are lower and not as serious as with bypass,” he said.

“Gastric bypass is considered more invasive than banding,” agreed Dr. Holterman. Banding is reversible, and it also results in more gradual weight loss since it relies entirely on restricting gastric capacity rather than also on reducing absorption like bypass does, she noted. Dr. Holterman said she prefers an approach that tries banding first, reserving bypass as a later option if needed.

Regardless of which surgical approach is best, now that the field has arrived at a consensus that adolescent surgery is appropriate for patients with BMIs as low as 35 kg/m

Dr. Holterman said that she thinks starting a study of this approach is now reasonable.

The National Institutes of Health established the adult criteria in 1991, and they have not been revised since, Dr. Nadler noted. “I think the operation is safe enough that you can broaden the application. The adult criteria are expanding, and perhaps the adolescent criteria will expand, too.”

Disclosures: Dr. Inge has received research funding from Ethicon Inc., a company that markets a gastric banding device. Dr. Pratt has served as a consultant to Covidien, a company that works with Allergan Inc. to market a gastric banding device. Dr. Nadler has received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

Diabetes, sleep apnea, and nonalcoholic steatohepatitis are 'reversible' with bariatric surgery in adolescents.

Source DR. PRATT

The surgery 'is preventive in the sense that patients have more severe comorbidities if you wait.'

Source DR. HOLTERMAN

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE