Bruce Jancin

KEYSTONE, COLO. — Why are the Juvenile Diabetes Research Foundation and many of the nation's foremost diabetes researchers pressing full speed ahead to develop an artificial pancreas?

Quite simply, because multiple real-world studies show that current usual therapy of type 1 diabetes fails to achieve target hemoglobin A_1c levels in more than half of patients.

And while more intensified management using insulin pumps and frequent daily or continuous glucose monitoring (CGM) effectively lowers HbA_1c values for some patients outside the artificial world of clinical trials, it does not work for everybody – especially teenagers, many of whom do not want to have to deal with diabetes continuously, Dr. Georgeanna J. Klingensmith said at the conference, sponsored by the Children's Diabetes Foundation at Denver.

“An artificial pancreas may remove enough of the human error and hassle factor to allow more patients to achieve success, we hope. A cure for adolescence would also help,” quipped Dr. Klingensmith, chief of the pediatric clinic at the Barbara Davis Center for Childhood Diabetes and professor of pediatrics at the University of Colorado, Denver.

A JDRF-sponsored study of CGM as it is used in routine clinical care underscores the adolescent adherence problem. Patients were instructed in the use of the device and were in frequent contact with their health care provider for the first month, then told to call as needed. By 6 months, 64% of the patients who were aged 25 years or older were using their CGM sensor at least 6 days a week, as instructed. So were 25% of 8- to 14-year-olds, but only 19% of 15- to 24-year-olds. Moreover, 21% of all 15- to 24-year-olds were not wearing the device at all in month 6 (Diabetes Care 2010;33:17–22).

Predictors of successful use of CGM at month 6 included age 25 years or greater, more frequent self-testing of blood glucose prior to going on CGM, wearing the device 6 days or more a week during the first month, and success in keeping blood glucose readings in the 70- to 180-mg/dL range during month 1.

Dr. Klingensmith cited among several examples of the state of real-world diabetes care the Hvidøre Study Group. In this 21-center study of roughly 2,000 pediatric type 1 diabetes patients, mostly in Europe, only a single center met the 2009 International Society for Pediatric and Adolescent Diabetes (ISPAD) consensus guideline that all children should have an HbA_1c below 7.5%. The mean HbA_1c was 8.2% (Diabetes Care 2007;30:2245–50).

Similarly, in 2,999 type 1 diabetes patients at six U.S. centers participating in the SEARCH for Diabetes in Youth Study, in which Dr. Klingensmith was a co-investigator, mean HbA_1c was 8.3%, with only 44% of type 1 patients meeting American Diabetes Association HbA_1c age-based targets (J. Pediatr. 2009;155:668–72).

Most of the factors associated with HbA_1c in a multivariate analysis of SEARCH were nonmodifiable: age, diabetes duration, race, parental education, insurance status, household income. The only two independent modifiable factors were insulin regimen – patients on pump therapy had a mean HbA_1c of 8.0%, significantly lower than any other regimen – and frequency of blood glucose testing.

In 2009, at the Barbara Davis Center for Childhood Diabetes in Denver, of 2,437 patients diagnosed with type 1 diabetes more than 3 months earlier, the median HbA_1c was 8.2% in children younger than 6 years old, 8.2% in 6- to 12-year-olds, and 8.7% in those aged 13–18 years. Plus, teens accounted for 75% of all patients with a median HbA_1c greater than 10%, Dr. Klingensmith continued.

An artificial pancreas, or “closed loop” system, would entail reliable automated guidance of insulin pump dosing based on input from CGM coupled with predictive algorithms for avoidance of severe hypoglycemia, she said.

Disclosures: Dr. Klingensmith said her work is supported by research grants from the National Institutes of Health and Centers for Disease Control and Prevention.

KEYSTONE, COLO. — Why are the Juvenile Diabetes Research Foundation and many of the nation's foremost diabetes researchers pressing full speed ahead to develop an artificial pancreas?

Quite simply, because multiple real-world studies show that current usual therapy of type 1 diabetes fails to achieve target hemoglobin A_1c levels in more than half of patients.

And while more intensified management using insulin pumps and frequent daily or continuous glucose monitoring (CGM) effectively lowers HbA_1c values for some patients outside the artificial world of clinical trials, it does not work for everybody – especially teenagers, many of whom do not want to have to deal with diabetes continuously, Dr. Georgeanna J. Klingensmith said at the conference, sponsored by the Children's Diabetes Foundation at Denver.

“An artificial pancreas may remove enough of the human error and hassle factor to allow more patients to achieve success, we hope. A cure for adolescence would also help,” quipped Dr. Klingensmith, chief of the pediatric clinic at the Barbara Davis Center for Childhood Diabetes and professor of pediatrics at the University of Colorado, Denver.

A JDRF-sponsored study of CGM as it is used in routine clinical care underscores the adolescent adherence problem. Patients were instructed in the use of the device and were in frequent contact with their health care provider for the first month, then told to call as needed. By 6 months, 64% of the patients who were aged 25 years or older were using their CGM sensor at least 6 days a week, as instructed. So were 25% of 8- to 14-year-olds, but only 19% of 15- to 24-year-olds. Moreover, 21% of all 15- to 24-year-olds were not wearing the device at all in month 6 (Diabetes Care 2010;33:17–22).

Predictors of successful use of CGM at month 6 included age 25 years or greater, more frequent self-testing of blood glucose prior to going on CGM, wearing the device 6 days or more a week during the first month, and success in keeping blood glucose readings in the 70- to 180-mg/dL range during month 1.

Dr. Klingensmith cited among several examples of the state of real-world diabetes care the Hvidøre Study Group. In this 21-center study of roughly 2,000 pediatric type 1 diabetes patients, mostly in Europe, only a single center met the 2009 International Society for Pediatric and Adolescent Diabetes (ISPAD) consensus guideline that all children should have an HbA_1c below 7.5%. The mean HbA_1c was 8.2% (Diabetes Care 2007;30:2245–50).

Similarly, in 2,999 type 1 diabetes patients at six U.S. centers participating in the SEARCH for Diabetes in Youth Study, in which Dr. Klingensmith was a co-investigator, mean HbA_1c was 8.3%, with only 44% of type 1 patients meeting American Diabetes Association HbA_1c age-based targets (J. Pediatr. 2009;155:668–72).

Most of the factors associated with HbA_1c in a multivariate analysis of SEARCH were nonmodifiable: age, diabetes duration, race, parental education, insurance status, household income. The only two independent modifiable factors were insulin regimen – patients on pump therapy had a mean HbA_1c of 8.0%, significantly lower than any other regimen – and frequency of blood glucose testing.

In 2009, at the Barbara Davis Center for Childhood Diabetes in Denver, of 2,437 patients diagnosed with type 1 diabetes more than 3 months earlier, the median HbA_1c was 8.2% in children younger than 6 years old, 8.2% in 6- to 12-year-olds, and 8.7% in those aged 13–18 years. Plus, teens accounted for 75% of all patients with a median HbA_1c greater than 10%, Dr. Klingensmith continued.

An artificial pancreas, or “closed loop” system, would entail reliable automated guidance of insulin pump dosing based on input from CGM coupled with predictive algorithms for avoidance of severe hypoglycemia, she said.

Disclosures: Dr. Klingensmith said her work is supported by research grants from the National Institutes of Health and Centers for Disease Control and Prevention.

KEYSTONE, COLO. — Why are the Juvenile Diabetes Research Foundation and many of the nation's foremost diabetes researchers pressing full speed ahead to develop an artificial pancreas?

Quite simply, because multiple real-world studies show that current usual therapy of type 1 diabetes fails to achieve target hemoglobin A_1c levels in more than half of patients.

And while more intensified management using insulin pumps and frequent daily or continuous glucose monitoring (CGM) effectively lowers HbA_1c values for some patients outside the artificial world of clinical trials, it does not work for everybody – especially teenagers, many of whom do not want to have to deal with diabetes continuously, Dr. Georgeanna J. Klingensmith said at the conference, sponsored by the Children's Diabetes Foundation at Denver.

“An artificial pancreas may remove enough of the human error and hassle factor to allow more patients to achieve success, we hope. A cure for adolescence would also help,” quipped Dr. Klingensmith, chief of the pediatric clinic at the Barbara Davis Center for Childhood Diabetes and professor of pediatrics at the University of Colorado, Denver.

A JDRF-sponsored study of CGM as it is used in routine clinical care underscores the adolescent adherence problem. Patients were instructed in the use of the device and were in frequent contact with their health care provider for the first month, then told to call as needed. By 6 months, 64% of the patients who were aged 25 years or older were using their CGM sensor at least 6 days a week, as instructed. So were 25% of 8- to 14-year-olds, but only 19% of 15- to 24-year-olds. Moreover, 21% of all 15- to 24-year-olds were not wearing the device at all in month 6 (Diabetes Care 2010;33:17–22).

Predictors of successful use of CGM at month 6 included age 25 years or greater, more frequent self-testing of blood glucose prior to going on CGM, wearing the device 6 days or more a week during the first month, and success in keeping blood glucose readings in the 70- to 180-mg/dL range during month 1.

Dr. Klingensmith cited among several examples of the state of real-world diabetes care the Hvidøre Study Group. In this 21-center study of roughly 2,000 pediatric type 1 diabetes patients, mostly in Europe, only a single center met the 2009 International Society for Pediatric and Adolescent Diabetes (ISPAD) consensus guideline that all children should have an HbA_1c below 7.5%. The mean HbA_1c was 8.2% (Diabetes Care 2007;30:2245–50).

Similarly, in 2,999 type 1 diabetes patients at six U.S. centers participating in the SEARCH for Diabetes in Youth Study, in which Dr. Klingensmith was a co-investigator, mean HbA_1c was 8.3%, with only 44% of type 1 patients meeting American Diabetes Association HbA_1c age-based targets (J. Pediatr. 2009;155:668–72).

Most of the factors associated with HbA_1c in a multivariate analysis of SEARCH were nonmodifiable: age, diabetes duration, race, parental education, insurance status, household income. The only two independent modifiable factors were insulin regimen – patients on pump therapy had a mean HbA_1c of 8.0%, significantly lower than any other regimen – and frequency of blood glucose testing.

In 2009, at the Barbara Davis Center for Childhood Diabetes in Denver, of 2,437 patients diagnosed with type 1 diabetes more than 3 months earlier, the median HbA_1c was 8.2% in children younger than 6 years old, 8.2% in 6- to 12-year-olds, and 8.7% in those aged 13–18 years. Plus, teens accounted for 75% of all patients with a median HbA_1c greater than 10%, Dr. Klingensmith continued.

An artificial pancreas, or “closed loop” system, would entail reliable automated guidance of insulin pump dosing based on input from CGM coupled with predictive algorithms for avoidance of severe hypoglycemia, she said.

Disclosures: Dr. Klingensmith said her work is supported by research grants from the National Institutes of Health and Centers for Disease Control and Prevention.

KEYSTONE, COLO. — A multidisciplinary position statement on aspirin for primary prevention of cardiovascular events in diabetic patients raises more questions than it answers, especially with regard to the appropriate course of action in adults with type 1 diabetes.

The statement, jointly published by the American Diabetes Association, American Heart Association, and American College of Cardiology, concluded: “The effect of aspirin for primary prevention of CVD events in adults with diabetes is currently unclear.”

“And that's for type 2 diabetes. The statement doesn't even address type 1,” Dr. Irl B. Hirsch said at the conference, which was was sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver.

The expert panel sidestepped the issue of aspirin for primary prevention of cardiovascular events in type 1 diabetic adults because the relevant randomized trial evidence is so scanty. Of the nine published randomized trials that have examined aspirin for primary prevention and included subjects with diabetes, six did not focus specifically on diabetic patients. And in three of these six – the Physicians' Health Study, the British Medical Doctors, and the Thrombosis Prevention Trial – a mere 1%–2% of participants had diabetes.

Moreover, two of the three trials that focused on persons with diabetes included mainly or exclusively patients with type 2 diabetes. Only one randomized trial included a substantial population of type 1 diabetic patients, noted Dr. Hirsch, professor of medicine and holder of the Diabetes Treatment and Teaching Chair at the University of Washington, Seattle.

The expert panel performed a new meta-analysis using the three trials in diabetic patients plus the diabetic subgroups from the six other trials. They found prophylactic aspirin was associated with a 9% decrease in the risk of fatal and nonfatal MI and a 15% reduction in the risk of stroke, consistent with what was deemed a “modest” but statistically nonsignificant benefit (Diabetes Care 2010;33:1395–402).

The panel determined that the excess risk of gastrointestinal bleeding associated with aspirin for primary cardiovascular prevention in real-world settings may be 1–5 events per 1,000 treated patients per year. Thus, in persons whose risk of CV events is greater than 1% per year, the number of CV events prevented is likely to be equal to or greater than the number of bleeding events induced.

Based upon this reasoning, the panel concluded that low-dose aspirin at 75–162 mg/day is reasonable for adults with type 2 diabetes and no previous history of vascular disease whose 10-year estimated risk of cardiovascular events exceeds 10%, so long as they aren't at increased bleeding risk based upon medical history or concurrent use of other drugs that raise bleeding risk. Most diabetic men over age 50 and diabetic women over age 60 who have one or more of the standard major cardiovascular risk factors would fall into this category.

The ADA/AHA/ACC position statement recommended against aspirin for prevention of cardiovascular events in adult diabetics whose 10-year risk is under 5%. This would typically be most diabetic men under age 50 and women under age 60 without dyslipidemia, smoking, hypertension, albuminuria, or a family history of premature cardiovascular disease (Diabetes Care 2010;33:1395–402).

Low-dose aspirin might be considered for primary prevention on a case-by-case basis in diabetic patients at intermediate cardiovascular risk until further research is available.

Two major ongoing clinical trials will add badly needed additional information. A Study of Cardiovascular Events in Diabetes (ASCEND) is a U.K. study looking at the impact of 100 mg/day of aspirin versus placebo in 10,000 men and women over age 40 with either type 1 or 2 diabetes and no prior vascular events. The Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) is an Italian study with a planned enrollment of nearly 5,200 diabetic adults over age 50.

In the absence of solid data on the impact of aspirin for primary prevention in adults with type 1 diabetes, Dr. Hirsch is applying the new recommendations for patients with type 2 disease to his type 1 patients as well. He recommended two “excellent” cardiovascular risk prediction tools for smartphones for use in the clinic: the UKPDS Risk Engine, at www.dtu.ox.ac.uk/riskengine/index.phpwww.diabetes.org/phd

These risk engines are valuable because, as the position statement points out, aspirin is not given in a vacuum. For example, a diabetic patient with an estimated 20% 10-year risk of a major cardiovascular event based on hypertension and dyslipidemia would have that risk fall to 13% by taking a statin, with a further reduction in risk to 10% with optimal BP control. Thus, effective treatment of modifiable risk factors makes the aspirin risk-benefit decision more complex.

Some of the other medical risk management issues in aging adults with type 1 diabetes have more clear-cut answers than the aspirin question. In general, all adults over age 40 with type 1 diabetes should be on statin therapy, in Dr. Hirsch's view, particularly if albuminuria is present.

ACE inhibitors or angiotensin receptor blockers should be used liberally in adults with type 1 diabetes, he added.

Risk assessment tools can help guide clinical decisions, Dr. Irl B. Hirsch said.

Source Courtesy Ruth Hirsch

Disclosures: Dr. Hirsch disclosed having no financial conflicts.

KEYSTONE, COLO. — A multidisciplinary position statement on aspirin for primary prevention of cardiovascular events in diabetic patients raises more questions than it answers, especially with regard to the appropriate course of action in adults with type 1 diabetes.

The statement, jointly published by the American Diabetes Association, American Heart Association, and American College of Cardiology, concluded: “The effect of aspirin for primary prevention of CVD events in adults with diabetes is currently unclear.”

“And that's for type 2 diabetes. The statement doesn't even address type 1,” Dr. Irl B. Hirsch said at the conference, which was was sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver.

The expert panel sidestepped the issue of aspirin for primary prevention of cardiovascular events in type 1 diabetic adults because the relevant randomized trial evidence is so scanty. Of the nine published randomized trials that have examined aspirin for primary prevention and included subjects with diabetes, six did not focus specifically on diabetic patients. And in three of these six – the Physicians' Health Study, the British Medical Doctors, and the Thrombosis Prevention Trial – a mere 1%–2% of participants had diabetes.

Moreover, two of the three trials that focused on persons with diabetes included mainly or exclusively patients with type 2 diabetes. Only one randomized trial included a substantial population of type 1 diabetic patients, noted Dr. Hirsch, professor of medicine and holder of the Diabetes Treatment and Teaching Chair at the University of Washington, Seattle.

The expert panel performed a new meta-analysis using the three trials in diabetic patients plus the diabetic subgroups from the six other trials. They found prophylactic aspirin was associated with a 9% decrease in the risk of fatal and nonfatal MI and a 15% reduction in the risk of stroke, consistent with what was deemed a “modest” but statistically nonsignificant benefit (Diabetes Care 2010;33:1395–402).

The panel determined that the excess risk of gastrointestinal bleeding associated with aspirin for primary cardiovascular prevention in real-world settings may be 1–5 events per 1,000 treated patients per year. Thus, in persons whose risk of CV events is greater than 1% per year, the number of CV events prevented is likely to be equal to or greater than the number of bleeding events induced.

Based upon this reasoning, the panel concluded that low-dose aspirin at 75–162 mg/day is reasonable for adults with type 2 diabetes and no previous history of vascular disease whose 10-year estimated risk of cardiovascular events exceeds 10%, so long as they aren't at increased bleeding risk based upon medical history or concurrent use of other drugs that raise bleeding risk. Most diabetic men over age 50 and diabetic women over age 60 who have one or more of the standard major cardiovascular risk factors would fall into this category.

The ADA/AHA/ACC position statement recommended against aspirin for prevention of cardiovascular events in adult diabetics whose 10-year risk is under 5%. This would typically be most diabetic men under age 50 and women under age 60 without dyslipidemia, smoking, hypertension, albuminuria, or a family history of premature cardiovascular disease (Diabetes Care 2010;33:1395–402).

Low-dose aspirin might be considered for primary prevention on a case-by-case basis in diabetic patients at intermediate cardiovascular risk until further research is available.

Two major ongoing clinical trials will add badly needed additional information. A Study of Cardiovascular Events in Diabetes (ASCEND) is a U.K. study looking at the impact of 100 mg/day of aspirin versus placebo in 10,000 men and women over age 40 with either type 1 or 2 diabetes and no prior vascular events. The Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) is an Italian study with a planned enrollment of nearly 5,200 diabetic adults over age 50.

In the absence of solid data on the impact of aspirin for primary prevention in adults with type 1 diabetes, Dr. Hirsch is applying the new recommendations for patients with type 2 disease to his type 1 patients as well. He recommended two “excellent” cardiovascular risk prediction tools for smartphones for use in the clinic: the UKPDS Risk Engine, at www.dtu.ox.ac.uk/riskengine/index.phpwww.diabetes.org/phd

These risk engines are valuable because, as the position statement points out, aspirin is not given in a vacuum. For example, a diabetic patient with an estimated 20% 10-year risk of a major cardiovascular event based on hypertension and dyslipidemia would have that risk fall to 13% by taking a statin, with a further reduction in risk to 10% with optimal BP control. Thus, effective treatment of modifiable risk factors makes the aspirin risk-benefit decision more complex.

Some of the other medical risk management issues in aging adults with type 1 diabetes have more clear-cut answers than the aspirin question. In general, all adults over age 40 with type 1 diabetes should be on statin therapy, in Dr. Hirsch's view, particularly if albuminuria is present.

ACE inhibitors or angiotensin receptor blockers should be used liberally in adults with type 1 diabetes, he added.

Risk assessment tools can help guide clinical decisions, Dr. Irl B. Hirsch said.

Source Courtesy Ruth Hirsch

Disclosures: Dr. Hirsch disclosed having no financial conflicts.

KEYSTONE, COLO. — A multidisciplinary position statement on aspirin for primary prevention of cardiovascular events in diabetic patients raises more questions than it answers, especially with regard to the appropriate course of action in adults with type 1 diabetes.

The statement, jointly published by the American Diabetes Association, American Heart Association, and American College of Cardiology, concluded: “The effect of aspirin for primary prevention of CVD events in adults with diabetes is currently unclear.”

“And that's for type 2 diabetes. The statement doesn't even address type 1,” Dr. Irl B. Hirsch said at the conference, which was was sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver.

The expert panel sidestepped the issue of aspirin for primary prevention of cardiovascular events in type 1 diabetic adults because the relevant randomized trial evidence is so scanty. Of the nine published randomized trials that have examined aspirin for primary prevention and included subjects with diabetes, six did not focus specifically on diabetic patients. And in three of these six – the Physicians' Health Study, the British Medical Doctors, and the Thrombosis Prevention Trial – a mere 1%–2% of participants had diabetes.

Moreover, two of the three trials that focused on persons with diabetes included mainly or exclusively patients with type 2 diabetes. Only one randomized trial included a substantial population of type 1 diabetic patients, noted Dr. Hirsch, professor of medicine and holder of the Diabetes Treatment and Teaching Chair at the University of Washington, Seattle.

The expert panel performed a new meta-analysis using the three trials in diabetic patients plus the diabetic subgroups from the six other trials. They found prophylactic aspirin was associated with a 9% decrease in the risk of fatal and nonfatal MI and a 15% reduction in the risk of stroke, consistent with what was deemed a “modest” but statistically nonsignificant benefit (Diabetes Care 2010;33:1395–402).

The panel determined that the excess risk of gastrointestinal bleeding associated with aspirin for primary cardiovascular prevention in real-world settings may be 1–5 events per 1,000 treated patients per year. Thus, in persons whose risk of CV events is greater than 1% per year, the number of CV events prevented is likely to be equal to or greater than the number of bleeding events induced.

Based upon this reasoning, the panel concluded that low-dose aspirin at 75–162 mg/day is reasonable for adults with type 2 diabetes and no previous history of vascular disease whose 10-year estimated risk of cardiovascular events exceeds 10%, so long as they aren't at increased bleeding risk based upon medical history or concurrent use of other drugs that raise bleeding risk. Most diabetic men over age 50 and diabetic women over age 60 who have one or more of the standard major cardiovascular risk factors would fall into this category.

The ADA/AHA/ACC position statement recommended against aspirin for prevention of cardiovascular events in adult diabetics whose 10-year risk is under 5%. This would typically be most diabetic men under age 50 and women under age 60 without dyslipidemia, smoking, hypertension, albuminuria, or a family history of premature cardiovascular disease (Diabetes Care 2010;33:1395–402).

Low-dose aspirin might be considered for primary prevention on a case-by-case basis in diabetic patients at intermediate cardiovascular risk until further research is available.

Two major ongoing clinical trials will add badly needed additional information. A Study of Cardiovascular Events in Diabetes (ASCEND) is a U.K. study looking at the impact of 100 mg/day of aspirin versus placebo in 10,000 men and women over age 40 with either type 1 or 2 diabetes and no prior vascular events. The Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) is an Italian study with a planned enrollment of nearly 5,200 diabetic adults over age 50.

In the absence of solid data on the impact of aspirin for primary prevention in adults with type 1 diabetes, Dr. Hirsch is applying the new recommendations for patients with type 2 disease to his type 1 patients as well. He recommended two “excellent” cardiovascular risk prediction tools for smartphones for use in the clinic: the UKPDS Risk Engine, at www.dtu.ox.ac.uk/riskengine/index.phpwww.diabetes.org/phd

These risk engines are valuable because, as the position statement points out, aspirin is not given in a vacuum. For example, a diabetic patient with an estimated 20% 10-year risk of a major cardiovascular event based on hypertension and dyslipidemia would have that risk fall to 13% by taking a statin, with a further reduction in risk to 10% with optimal BP control. Thus, effective treatment of modifiable risk factors makes the aspirin risk-benefit decision more complex.

Some of the other medical risk management issues in aging adults with type 1 diabetes have more clear-cut answers than the aspirin question. In general, all adults over age 40 with type 1 diabetes should be on statin therapy, in Dr. Hirsch's view, particularly if albuminuria is present.

ACE inhibitors or angiotensin receptor blockers should be used liberally in adults with type 1 diabetes, he added.

Risk assessment tools can help guide clinical decisions, Dr. Irl B. Hirsch said.

Source Courtesy Ruth Hirsch

Disclosures: Dr. Hirsch disclosed having no financial conflicts.

Three noted pediatric rheumatologists who've won fame and success in academic research while also practicing medicine have two key words of advice for young physicians interested in developing similar dual careers: mentors matter!

“Make strategic decisions about where you go for mentoring,” Dr. Klaus Tenbrock advised.

Speaking before fellows-in-training at the annual European Congress of Rheumatology, Dr. Tenbrock cited his own experience: The great mentor in his life has been Dr. George Tsokos, now chief of the division of rheumatology at Beth Israel Deaconess Medical Center in Boston. Dr. Tenbrock moved to Massachusetts from Germany in order to train under Dr. Tsokos.

Dr. Tsokos' lab is said to have a pipeline to the Journal of Immunology. As a consequence, Dr. Tenbrock was able to get his pioneering studies on the importance of the cyclic AMP response modulator (CREM) in systemic lupus erythematosus (SLE) published in this prestigious, high-profile journal even though he was a young, unknown researcher.

“The CREM story has followed me through two-thirds of my career,” noted Dr. Tenbrock, now at the University of Aachen (Germany). Indeed, he has received more than 1 million euros in CREM research grants in the past 10 years.

Dr. Salvatore Albani said a helpful mentor is like a successful parent: “A good mentor is one who lets you grow.”

“You have to choose the right mentors,” agreed Dr. Virginia Pascual. “You have to choose the right collaborators. If you can have fun, it's much, much better — and I've had a lot of fun in my collaborations.”

She stressed that a dual research/clinical career is hard work and very time consuming. It requires passionate commitment. “But if you have the passion, my advice is to please pursue it,” urged Dr. Pascual, an investigator at the Baylor Institute for Immunology Research in Dallas.

Credited as the first person to amplify a gene using PCR, Dr. Pascual was already an established first-tier basic scientist before deciding to pursue a pediatric rheumatology fellowship. The additional clinical training took her out of the laboratory and brought an entirely new and richly rewarding dimension to her work: strong and enduring relationships with patients who are dealing with serious illnesses.

In the past several years, she has been “overjoyed” to see pharmaceutical companies undertaking clinical trials evaluating the type-1 interferon cytokine family as a novel therapeutic target in SLE, a hypothesis she and others developed.

“Studying humans is very, very important, in my opinion, to making a difference in what we do,” concurred Dr. Albani, professor and director of translational research for infectious and inflammatory diseases at the Sanford-Burnham Medical Research Institute in La Jolla, Calif.

The German scientific research establishment takes a somewhat different position. “Mouse work is an advantage, at least in Germany. I didn't get any money from the German Research Foundation until I started to work with mice,” Dr. Tenbrock recalled.

Dr. Albani observed that people who are willing to make the personal sacrifices required to pursue a dual research/clinical career share a common dream: “to find the cure, to find the explanation, to understand and contribute.” But when they do make an important discovery, most scientists find themselves in unfamiliar and treacherous waters. They are clueless about how to protect their intellectual property, design a product development plan, find funding sources, and convince them to invest.

Speaking from the vantage point of having founded a biotech company and personally caring for approximately 80 patients, Dr. Albani offered a cautionary note to his fresh-faced audience: “As scientists, we think the idea is everything. From my personal experience, I have to tell you the bad news that having a great idea is just the modest initial start of a long process, and you will lose control when the process is successful.”

“We race toward publication, we drive to become famous, and in reality we miss the opportunity to protect our property — our ideas — because we are not knowledgeable about the fact that if the idea is not protected it will be impossible to convince anyone to fund it. It will not have any commercial value,” he explained.

Unfortunately, the technology transfer offices in many universities aren't helpful. “They treat intellectual property as a hot potato which they like to get rid of quickly because of the costs,” Dr. Albani warned.

The costs of developing strong protection for intellectual property — often amounting to hundreds of thousands of dollars — have eaten up the developmental budgets of many a young scientist/inventor, leaving them unable to move on to preclinical studies, which in turn are a prerequisite to human trials.

“This is where a lot of technologies die,” according to Dr. Albani.

He stressed the importance of becoming a part of international collaborative research networks having shared interests. This is how the real science is getting done today.

“At this point, in this world, it's very important to think in a global fashion. The difference between success and failure is understanding the difference between fighting for a common goal with people having different views and different expertise, as opposed to going for glory on your own,” he said. “You need to be able to build bridges to others, you need to be able to question yourself, be humble, and find ways to accomplish the next step while working together with others.”

Dr. Albani is a cofounder of the Eureka Institute for Translational Medicine, an international education project aimed at preparing researchers for the challenges they will face in developing their ideas and bringing new products to market.

Disclosures: Dr. Tenbrock, Dr. Albani, and Dr. Pascual declared that their research is funded mainly by government agencies and foundations.

Most scientists are clueless about how to protect their intellectual property.

Source DR. ALBANI

Three noted pediatric rheumatologists who've won fame and success in academic research while also practicing medicine have two key words of advice for young physicians interested in developing similar dual careers: mentors matter!

“Make strategic decisions about where you go for mentoring,” Dr. Klaus Tenbrock advised.

Speaking before fellows-in-training at the annual European Congress of Rheumatology, Dr. Tenbrock cited his own experience: The great mentor in his life has been Dr. George Tsokos, now chief of the division of rheumatology at Beth Israel Deaconess Medical Center in Boston. Dr. Tenbrock moved to Massachusetts from Germany in order to train under Dr. Tsokos.

Dr. Tsokos' lab is said to have a pipeline to the Journal of Immunology. As a consequence, Dr. Tenbrock was able to get his pioneering studies on the importance of the cyclic AMP response modulator (CREM) in systemic lupus erythematosus (SLE) published in this prestigious, high-profile journal even though he was a young, unknown researcher.

“The CREM story has followed me through two-thirds of my career,” noted Dr. Tenbrock, now at the University of Aachen (Germany). Indeed, he has received more than 1 million euros in CREM research grants in the past 10 years.

Dr. Salvatore Albani said a helpful mentor is like a successful parent: “A good mentor is one who lets you grow.”

“You have to choose the right mentors,” agreed Dr. Virginia Pascual. “You have to choose the right collaborators. If you can have fun, it's much, much better — and I've had a lot of fun in my collaborations.”

She stressed that a dual research/clinical career is hard work and very time consuming. It requires passionate commitment. “But if you have the passion, my advice is to please pursue it,” urged Dr. Pascual, an investigator at the Baylor Institute for Immunology Research in Dallas.

Credited as the first person to amplify a gene using PCR, Dr. Pascual was already an established first-tier basic scientist before deciding to pursue a pediatric rheumatology fellowship. The additional clinical training took her out of the laboratory and brought an entirely new and richly rewarding dimension to her work: strong and enduring relationships with patients who are dealing with serious illnesses.

In the past several years, she has been “overjoyed” to see pharmaceutical companies undertaking clinical trials evaluating the type-1 interferon cytokine family as a novel therapeutic target in SLE, a hypothesis she and others developed.

“Studying humans is very, very important, in my opinion, to making a difference in what we do,” concurred Dr. Albani, professor and director of translational research for infectious and inflammatory diseases at the Sanford-Burnham Medical Research Institute in La Jolla, Calif.

The German scientific research establishment takes a somewhat different position. “Mouse work is an advantage, at least in Germany. I didn't get any money from the German Research Foundation until I started to work with mice,” Dr. Tenbrock recalled.

Dr. Albani observed that people who are willing to make the personal sacrifices required to pursue a dual research/clinical career share a common dream: “to find the cure, to find the explanation, to understand and contribute.” But when they do make an important discovery, most scientists find themselves in unfamiliar and treacherous waters. They are clueless about how to protect their intellectual property, design a product development plan, find funding sources, and convince them to invest.

Speaking from the vantage point of having founded a biotech company and personally caring for approximately 80 patients, Dr. Albani offered a cautionary note to his fresh-faced audience: “As scientists, we think the idea is everything. From my personal experience, I have to tell you the bad news that having a great idea is just the modest initial start of a long process, and you will lose control when the process is successful.”

“We race toward publication, we drive to become famous, and in reality we miss the opportunity to protect our property — our ideas — because we are not knowledgeable about the fact that if the idea is not protected it will be impossible to convince anyone to fund it. It will not have any commercial value,” he explained.

Unfortunately, the technology transfer offices in many universities aren't helpful. “They treat intellectual property as a hot potato which they like to get rid of quickly because of the costs,” Dr. Albani warned.

The costs of developing strong protection for intellectual property — often amounting to hundreds of thousands of dollars — have eaten up the developmental budgets of many a young scientist/inventor, leaving them unable to move on to preclinical studies, which in turn are a prerequisite to human trials.

“This is where a lot of technologies die,” according to Dr. Albani.

He stressed the importance of becoming a part of international collaborative research networks having shared interests. This is how the real science is getting done today.

“At this point, in this world, it's very important to think in a global fashion. The difference between success and failure is understanding the difference between fighting for a common goal with people having different views and different expertise, as opposed to going for glory on your own,” he said. “You need to be able to build bridges to others, you need to be able to question yourself, be humble, and find ways to accomplish the next step while working together with others.”

Dr. Albani is a cofounder of the Eureka Institute for Translational Medicine, an international education project aimed at preparing researchers for the challenges they will face in developing their ideas and bringing new products to market.

Disclosures: Dr. Tenbrock, Dr. Albani, and Dr. Pascual declared that their research is funded mainly by government agencies and foundations.

Most scientists are clueless about how to protect their intellectual property.

Source DR. ALBANI

Three noted pediatric rheumatologists who've won fame and success in academic research while also practicing medicine have two key words of advice for young physicians interested in developing similar dual careers: mentors matter!

“Make strategic decisions about where you go for mentoring,” Dr. Klaus Tenbrock advised.

Speaking before fellows-in-training at the annual European Congress of Rheumatology, Dr. Tenbrock cited his own experience: The great mentor in his life has been Dr. George Tsokos, now chief of the division of rheumatology at Beth Israel Deaconess Medical Center in Boston. Dr. Tenbrock moved to Massachusetts from Germany in order to train under Dr. Tsokos.

Dr. Tsokos' lab is said to have a pipeline to the Journal of Immunology. As a consequence, Dr. Tenbrock was able to get his pioneering studies on the importance of the cyclic AMP response modulator (CREM) in systemic lupus erythematosus (SLE) published in this prestigious, high-profile journal even though he was a young, unknown researcher.

“The CREM story has followed me through two-thirds of my career,” noted Dr. Tenbrock, now at the University of Aachen (Germany). Indeed, he has received more than 1 million euros in CREM research grants in the past 10 years.

Dr. Salvatore Albani said a helpful mentor is like a successful parent: “A good mentor is one who lets you grow.”

“You have to choose the right mentors,” agreed Dr. Virginia Pascual. “You have to choose the right collaborators. If you can have fun, it's much, much better — and I've had a lot of fun in my collaborations.”

She stressed that a dual research/clinical career is hard work and very time consuming. It requires passionate commitment. “But if you have the passion, my advice is to please pursue it,” urged Dr. Pascual, an investigator at the Baylor Institute for Immunology Research in Dallas.

Credited as the first person to amplify a gene using PCR, Dr. Pascual was already an established first-tier basic scientist before deciding to pursue a pediatric rheumatology fellowship. The additional clinical training took her out of the laboratory and brought an entirely new and richly rewarding dimension to her work: strong and enduring relationships with patients who are dealing with serious illnesses.

In the past several years, she has been “overjoyed” to see pharmaceutical companies undertaking clinical trials evaluating the type-1 interferon cytokine family as a novel therapeutic target in SLE, a hypothesis she and others developed.

“Studying humans is very, very important, in my opinion, to making a difference in what we do,” concurred Dr. Albani, professor and director of translational research for infectious and inflammatory diseases at the Sanford-Burnham Medical Research Institute in La Jolla, Calif.

The German scientific research establishment takes a somewhat different position. “Mouse work is an advantage, at least in Germany. I didn't get any money from the German Research Foundation until I started to work with mice,” Dr. Tenbrock recalled.

Dr. Albani observed that people who are willing to make the personal sacrifices required to pursue a dual research/clinical career share a common dream: “to find the cure, to find the explanation, to understand and contribute.” But when they do make an important discovery, most scientists find themselves in unfamiliar and treacherous waters. They are clueless about how to protect their intellectual property, design a product development plan, find funding sources, and convince them to invest.

Speaking from the vantage point of having founded a biotech company and personally caring for approximately 80 patients, Dr. Albani offered a cautionary note to his fresh-faced audience: “As scientists, we think the idea is everything. From my personal experience, I have to tell you the bad news that having a great idea is just the modest initial start of a long process, and you will lose control when the process is successful.”

“We race toward publication, we drive to become famous, and in reality we miss the opportunity to protect our property — our ideas — because we are not knowledgeable about the fact that if the idea is not protected it will be impossible to convince anyone to fund it. It will not have any commercial value,” he explained.

Unfortunately, the technology transfer offices in many universities aren't helpful. “They treat intellectual property as a hot potato which they like to get rid of quickly because of the costs,” Dr. Albani warned.

The costs of developing strong protection for intellectual property — often amounting to hundreds of thousands of dollars — have eaten up the developmental budgets of many a young scientist/inventor, leaving them unable to move on to preclinical studies, which in turn are a prerequisite to human trials.

“This is where a lot of technologies die,” according to Dr. Albani.

He stressed the importance of becoming a part of international collaborative research networks having shared interests. This is how the real science is getting done today.

“At this point, in this world, it's very important to think in a global fashion. The difference between success and failure is understanding the difference between fighting for a common goal with people having different views and different expertise, as opposed to going for glory on your own,” he said. “You need to be able to build bridges to others, you need to be able to question yourself, be humble, and find ways to accomplish the next step while working together with others.”

Dr. Albani is a cofounder of the Eureka Institute for Translational Medicine, an international education project aimed at preparing researchers for the challenges they will face in developing their ideas and bringing new products to market.

Disclosures: Dr. Tenbrock, Dr. Albani, and Dr. Pascual declared that their research is funded mainly by government agencies and foundations.

Most scientists are clueless about how to protect their intellectual property.

Source DR. ALBANI

The European Commission and the European League Against Rheumatism have joined forces in an ambitious 3-year project that is designed to optimize the care of patients with musculoskeletal conditions all across Europe.

The new European Musculoskeletal Conditions Surveillance and Information Network (www.eumusc.net

The eumusc.net project is funded by a grant of nearly 1 million euros from the European Commission along with 300,000 euros from EULAR. After the project ends in 2013, EULAR will take it over, according to Dr. Woolf, professor of rheumatology at the Institute of Health Care Research of Peninsula College of Medicine and Dentistry, Plymouth, England.

“The goal is to improve quality of care [and] to harmonize care so there is more equity across countries and within countries,” the rheumatologist said. “Wherever you're being treated, you should have the same chance of doing well or going into remission.”

“We're not going to come up with new guidelines because we already have excellent guidelines for the management of osteoarthritis and rheumatoid arthritis from EULAR. It's time to get them implemented,” he continued.

The eumusc.net project was granted funding by the European Union Health Program in a competitive bidding process. EU health officials were persuaded to make improved care for musculoskeletal conditions a high priority, in part on the strength of data showing that osteoarthritis is tied with disorders related to alcohol abuse for fourth place on the top-10 list of causes of years lived with disability in high-income countries.

Only unipolar depression, dementias, and adult-onset hearing loss ranked higher. Osteoarthritis was rated higher than cerebrovascular disease, chronic obstructive pulmonary disease, diabetes, and other major chronic diseases. These are the sorts of data that grab the attention of social security and health department officials.

In the United Kingdom, “musculoskeletal conditions are the No. 3 reason for general practitioner consultations. One can put a price on that, and it's very impressive,” Dr. Woolf said.

Although mortality may not be the best indicator of the societal impact of musculoskeletal disorders, Dr. Josef S. Smolen said it's a factor that should not be underestimated.

“If a woman breaks a hip, she has the same life expectancy as a metastasized breast cancer patient, and that's not sufficiently appreciated,” observed Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna, 1 of 23 European medical centers and patient organizations serving as partners in eumusc.net.

Dr. Alan J. Silman sounded a note of skepticism regarding eumusc.net, saying that the project sounds like an effort to “harmonize toward the mediocre.”

“We should be encouraging diversity and variability.” Harmonization as a goal “won't work” and “is not something we should ascribe to,” argued Dr. Silman, professor of rheumatic disease epidemiology at the University of Manchester (England).

He observed that virtually all discussion of the eumusc.net project has focused on developing and monitoring standards of care and process measurement. Yet what constitutes good outcomes for patients with many rheumatic diseases hasn't been well established.

“I'm concerned that we're going to get lost in terms of process, numbers of people on drugs, or waiting times for [dual-energy x-ray absorptiometry] scans, or how quickly people go onto [anti–tumor necrosis factor] drugs in the south of Sweden,” he said. “I just wonder if we're deluding ourselves if we think that if we have so many patients on biologics, that's the end of the story.”

In the United Kingdom, “we've got the British Society of Rheumatology Biologics Registry, and we know from that [that] there's a substantial proportion of patients being maintained on biologic agents who've not had a clinical response. We can say, 'Look how wonderful it is that the number of patients on biologics is increasing,' but surely we're failing those patients who aren't having a clinical response, and we're not doing anything further, Dr. Silman said.”

Disclosures: Dr. Woolf, Dr. Smolen, and Dr. Silman had no financial conflicts of interest that were relevant to the report.

'If a woman breaks a hip, she has the same life expectancy as a metastasized breast cancer patient.'

Source DR. SMOLEN

The European Commission and the European League Against Rheumatism have joined forces in an ambitious 3-year project that is designed to optimize the care of patients with musculoskeletal conditions all across Europe.

The new European Musculoskeletal Conditions Surveillance and Information Network (www.eumusc.net

The eumusc.net project is funded by a grant of nearly 1 million euros from the European Commission along with 300,000 euros from EULAR. After the project ends in 2013, EULAR will take it over, according to Dr. Woolf, professor of rheumatology at the Institute of Health Care Research of Peninsula College of Medicine and Dentistry, Plymouth, England.

“The goal is to improve quality of care [and] to harmonize care so there is more equity across countries and within countries,” the rheumatologist said. “Wherever you're being treated, you should have the same chance of doing well or going into remission.”

“We're not going to come up with new guidelines because we already have excellent guidelines for the management of osteoarthritis and rheumatoid arthritis from EULAR. It's time to get them implemented,” he continued.

The eumusc.net project was granted funding by the European Union Health Program in a competitive bidding process. EU health officials were persuaded to make improved care for musculoskeletal conditions a high priority, in part on the strength of data showing that osteoarthritis is tied with disorders related to alcohol abuse for fourth place on the top-10 list of causes of years lived with disability in high-income countries.

Only unipolar depression, dementias, and adult-onset hearing loss ranked higher. Osteoarthritis was rated higher than cerebrovascular disease, chronic obstructive pulmonary disease, diabetes, and other major chronic diseases. These are the sorts of data that grab the attention of social security and health department officials.

In the United Kingdom, “musculoskeletal conditions are the No. 3 reason for general practitioner consultations. One can put a price on that, and it's very impressive,” Dr. Woolf said.

Although mortality may not be the best indicator of the societal impact of musculoskeletal disorders, Dr. Josef S. Smolen said it's a factor that should not be underestimated.

“If a woman breaks a hip, she has the same life expectancy as a metastasized breast cancer patient, and that's not sufficiently appreciated,” observed Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna, 1 of 23 European medical centers and patient organizations serving as partners in eumusc.net.

Dr. Alan J. Silman sounded a note of skepticism regarding eumusc.net, saying that the project sounds like an effort to “harmonize toward the mediocre.”

“We should be encouraging diversity and variability.” Harmonization as a goal “won't work” and “is not something we should ascribe to,” argued Dr. Silman, professor of rheumatic disease epidemiology at the University of Manchester (England).

He observed that virtually all discussion of the eumusc.net project has focused on developing and monitoring standards of care and process measurement. Yet what constitutes good outcomes for patients with many rheumatic diseases hasn't been well established.

“I'm concerned that we're going to get lost in terms of process, numbers of people on drugs, or waiting times for [dual-energy x-ray absorptiometry] scans, or how quickly people go onto [anti–tumor necrosis factor] drugs in the south of Sweden,” he said. “I just wonder if we're deluding ourselves if we think that if we have so many patients on biologics, that's the end of the story.”

In the United Kingdom, “we've got the British Society of Rheumatology Biologics Registry, and we know from that [that] there's a substantial proportion of patients being maintained on biologic agents who've not had a clinical response. We can say, 'Look how wonderful it is that the number of patients on biologics is increasing,' but surely we're failing those patients who aren't having a clinical response, and we're not doing anything further, Dr. Silman said.”

Disclosures: Dr. Woolf, Dr. Smolen, and Dr. Silman had no financial conflicts of interest that were relevant to the report.

'If a woman breaks a hip, she has the same life expectancy as a metastasized breast cancer patient.'

Source DR. SMOLEN

The European Commission and the European League Against Rheumatism have joined forces in an ambitious 3-year project that is designed to optimize the care of patients with musculoskeletal conditions all across Europe.

The new European Musculoskeletal Conditions Surveillance and Information Network (www.eumusc.net

The eumusc.net project is funded by a grant of nearly 1 million euros from the European Commission along with 300,000 euros from EULAR. After the project ends in 2013, EULAR will take it over, according to Dr. Woolf, professor of rheumatology at the Institute of Health Care Research of Peninsula College of Medicine and Dentistry, Plymouth, England.

“The goal is to improve quality of care [and] to harmonize care so there is more equity across countries and within countries,” the rheumatologist said. “Wherever you're being treated, you should have the same chance of doing well or going into remission.”

“We're not going to come up with new guidelines because we already have excellent guidelines for the management of osteoarthritis and rheumatoid arthritis from EULAR. It's time to get them implemented,” he continued.

The eumusc.net project was granted funding by the European Union Health Program in a competitive bidding process. EU health officials were persuaded to make improved care for musculoskeletal conditions a high priority, in part on the strength of data showing that osteoarthritis is tied with disorders related to alcohol abuse for fourth place on the top-10 list of causes of years lived with disability in high-income countries.

Only unipolar depression, dementias, and adult-onset hearing loss ranked higher. Osteoarthritis was rated higher than cerebrovascular disease, chronic obstructive pulmonary disease, diabetes, and other major chronic diseases. These are the sorts of data that grab the attention of social security and health department officials.

In the United Kingdom, “musculoskeletal conditions are the No. 3 reason for general practitioner consultations. One can put a price on that, and it's very impressive,” Dr. Woolf said.

Although mortality may not be the best indicator of the societal impact of musculoskeletal disorders, Dr. Josef S. Smolen said it's a factor that should not be underestimated.

“If a woman breaks a hip, she has the same life expectancy as a metastasized breast cancer patient, and that's not sufficiently appreciated,” observed Dr. Smolen, professor and chairman of rheumatology at the Medical University of Vienna, 1 of 23 European medical centers and patient organizations serving as partners in eumusc.net.

Dr. Alan J. Silman sounded a note of skepticism regarding eumusc.net, saying that the project sounds like an effort to “harmonize toward the mediocre.”

“We should be encouraging diversity and variability.” Harmonization as a goal “won't work” and “is not something we should ascribe to,” argued Dr. Silman, professor of rheumatic disease epidemiology at the University of Manchester (England).

He observed that virtually all discussion of the eumusc.net project has focused on developing and monitoring standards of care and process measurement. Yet what constitutes good outcomes for patients with many rheumatic diseases hasn't been well established.

“I'm concerned that we're going to get lost in terms of process, numbers of people on drugs, or waiting times for [dual-energy x-ray absorptiometry] scans, or how quickly people go onto [anti–tumor necrosis factor] drugs in the south of Sweden,” he said. “I just wonder if we're deluding ourselves if we think that if we have so many patients on biologics, that's the end of the story.”

In the United Kingdom, “we've got the British Society of Rheumatology Biologics Registry, and we know from that [that] there's a substantial proportion of patients being maintained on biologic agents who've not had a clinical response. We can say, 'Look how wonderful it is that the number of patients on biologics is increasing,' but surely we're failing those patients who aren't having a clinical response, and we're not doing anything further, Dr. Silman said.”

Disclosures: Dr. Woolf, Dr. Smolen, and Dr. Silman had no financial conflicts of interest that were relevant to the report.

'If a woman breaks a hip, she has the same life expectancy as a metastasized breast cancer patient.'

Source DR. SMOLEN

ROME — Last year's approval of febuxostat as the first new gout medication in over 40 years appears to have triggered a sharp uptick in drug development for a disease many physicians consider long neglected. The recent approval of pegoticase is proof of the pudding.

Novel gout therapies in the developmental pipeline range from the high tech — a fully human monoclonal antibody to interleukin-1beta — to the low tech, as in cherry juice.

“I've got more than 100 gout patients in my practice on cherry juice concentrate,” Dr. Naomi Schlesinger said in an interview with

Her small retrospective study showed that consumption of 1 tablespoon of Brownwood Acres tart cherry juice concentrate twice daily — equivalent to eating 90-120 cherries — led to a 50% or greater reduction in acute gout attacks in 92% of treated patients, with no side effects. Prophylaxis with cherry juice concentrate is worth considering as an adjunct to urate-lowering therapy, said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at Robert Wood Johnson Medical School, New Brunswick, N.J.

Many patients over the years had told her they loved to eat cherries and thought they might be helpful. Eventually she came across a small 1950 study suggesting a preventive effect.

“I've looked at pomegranate juice, too. It didn't work,” she added.

The mechanism of benefit for cherry juice concentrate is an anti-inflammatory effect, the rheumatologist said. Her in vitro studies showed that cherry juice concentrate reduced by up to half interleukin-1-beta and tumor necrosis factor-alpha secretion by monocytes exposed to monosodium urate crystals.

In gout patients, cherry juice concentrate didn't lower serum urate levels; indeed, more than one-third of patients not on urate-lowering therapy who had averaged close to one attack per month remained attack free during 4-6 months on cherry juice concentrate despite an average serum urate level of 7.8 mg/dL.

Other novel gout therapies subjected to studies presented at the European congress included the anti-interleukin-1-beta monoclonal antibody canakinumab, a uricosuric drug known for now as RDEA594, and tranilast, which has been licensed in Japan for several decades as an oral mast cell inhibitor for treatment of asthma and allergic rhinitis.

Tranilast also has a potent serum uric acid—lowering effect, making it a potential therapy for chronic management of hyperuricemia in gout patients — one that already has a well-established track record for safety, according to Dr. Michael Kitt, executive vice president and chief medical officer at Nuon Therapeutics Inc., San Mateo, Calif.

He presented a preliminary study in which 49 healthy subjects who received 7 days of tranilast at 300, 600, or 900 mg daily showed dose-dependent 1.1- to 3.3- mg/dL reductions in serum uric acid. A phase-IIa study in hyperuricemic patients should be completed in time for presentation later this year at the American College of Rheumatology meeting, and a phase IIb study of tranilast plus allopurinol is just starting in gout patients. When commercialized, tranilast will be combined with allopurinol in a single tablet, Dr. Kitt said in an interview.

Dr. Schlesinger also presented a large phase II clinical trial in which canakinumab, the fully human anti-interleukin-1-beta monoclonal antibody, outperformed colchicine for the reduction of flares in gout patients starting allopurinol therapy.

The double-blind, multicenter, 24-week study included 432 gout patients starting allopurinol who were randomized to 16 weeks of colchicine at 0.5 mg/day, a single subcutaneous injection of canakinumab at 25, 50, 100, 200, or 300 mg, or monthly canakinumab injections at 50, 50, 25, and 25 mg.

The canakinumab regimens reduced the risk of one or more urate-lowering therapy-induced flares by 61%-80% compared with colchicine. Canakinumab also reduced the overall rate of flares by 48%-75% relative to colchicine.

Phase III studies are underway, and Novartis plans to file for marketing approval of canakinumab for the treatment and prevention of acute gout attacks by year's end. The monoclonal antibody is licensed as Ilaris for treatment of cryopyrin-associated periodic syndromes.

Dr. Fernando Perez-Ruiz presented a phase II study of RDEA594, a uricosuric drug that normalizes gout patients' underexcretion of uric acid by a novel mechanism: inhibition of reabsorption of uric acid in the proximal tubule of the kidney.

The study involved 123 hyperuricemic gout patients randomized to 4 weeks of RDEA594 at 200, 400, or 600 mg/day or placebo. All were on colchicine at 0.5-0.6 mg/day to reduce the rate of gout flares.

The primary end point — reduction of serum uric acid to less than 6 mg/dL after 4 weeks of treatment — was achieved in 45% of patients on the highest dose of RDEA594 and 0% of those on placebo. The median reduction in serum uric acid in patients on the highest dose was 38%, versus a 1% increase in the placebo arm.

Among the subset of patients with a baseline serum uric level below 10 mg/dL, as is the case for a large majority of gout patients seen in clinical practice, the response rate to the highest dose of RDEA594 was 58%. The side effect profile of RDEA594 was comparable to placebo, added Dr. Perez-Ruiz of Hospital de Cruces in Vizcaya, Spain.

Ardea Biosciences, San Diego, which is developing RDEA594, has not decided whether to take the drug into phase III trials as monotherapy or in combination with febuxostat, with which RDEA594 has shown synergistic effects, a company official said in an interview with

Disclosures: Dr. Schlesinger has received research grants from Brownwood Acres and Novartis. Dr. Kitt is employed by Nuon Therapeutics Inc. Dr. Perez-Ruiz is a consultant to Ardea Biosciences.

As a result of its anti-inflammatory effect, cherry juice concentrate halves levels of interleukin-1-beta and TNF-alpha.

Source DR. SCHLESINGER

ROME — Last year's approval of febuxostat as the first new gout medication in over 40 years appears to have triggered a sharp uptick in drug development for a disease many physicians consider long neglected. The recent approval of pegoticase is proof of the pudding.

Novel gout therapies in the developmental pipeline range from the high tech — a fully human monoclonal antibody to interleukin-1beta — to the low tech, as in cherry juice.

“I've got more than 100 gout patients in my practice on cherry juice concentrate,” Dr. Naomi Schlesinger said in an interview with

Her small retrospective study showed that consumption of 1 tablespoon of Brownwood Acres tart cherry juice concentrate twice daily — equivalent to eating 90-120 cherries — led to a 50% or greater reduction in acute gout attacks in 92% of treated patients, with no side effects. Prophylaxis with cherry juice concentrate is worth considering as an adjunct to urate-lowering therapy, said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at Robert Wood Johnson Medical School, New Brunswick, N.J.

Many patients over the years had told her they loved to eat cherries and thought they might be helpful. Eventually she came across a small 1950 study suggesting a preventive effect.

“I've looked at pomegranate juice, too. It didn't work,” she added.

The mechanism of benefit for cherry juice concentrate is an anti-inflammatory effect, the rheumatologist said. Her in vitro studies showed that cherry juice concentrate reduced by up to half interleukin-1-beta and tumor necrosis factor-alpha secretion by monocytes exposed to monosodium urate crystals.

In gout patients, cherry juice concentrate didn't lower serum urate levels; indeed, more than one-third of patients not on urate-lowering therapy who had averaged close to one attack per month remained attack free during 4-6 months on cherry juice concentrate despite an average serum urate level of 7.8 mg/dL.

Other novel gout therapies subjected to studies presented at the European congress included the anti-interleukin-1-beta monoclonal antibody canakinumab, a uricosuric drug known for now as RDEA594, and tranilast, which has been licensed in Japan for several decades as an oral mast cell inhibitor for treatment of asthma and allergic rhinitis.

Tranilast also has a potent serum uric acid—lowering effect, making it a potential therapy for chronic management of hyperuricemia in gout patients — one that already has a well-established track record for safety, according to Dr. Michael Kitt, executive vice president and chief medical officer at Nuon Therapeutics Inc., San Mateo, Calif.

He presented a preliminary study in which 49 healthy subjects who received 7 days of tranilast at 300, 600, or 900 mg daily showed dose-dependent 1.1- to 3.3- mg/dL reductions in serum uric acid. A phase-IIa study in hyperuricemic patients should be completed in time for presentation later this year at the American College of Rheumatology meeting, and a phase IIb study of tranilast plus allopurinol is just starting in gout patients. When commercialized, tranilast will be combined with allopurinol in a single tablet, Dr. Kitt said in an interview.

Dr. Schlesinger also presented a large phase II clinical trial in which canakinumab, the fully human anti-interleukin-1-beta monoclonal antibody, outperformed colchicine for the reduction of flares in gout patients starting allopurinol therapy.

The double-blind, multicenter, 24-week study included 432 gout patients starting allopurinol who were randomized to 16 weeks of colchicine at 0.5 mg/day, a single subcutaneous injection of canakinumab at 25, 50, 100, 200, or 300 mg, or monthly canakinumab injections at 50, 50, 25, and 25 mg.

The canakinumab regimens reduced the risk of one or more urate-lowering therapy-induced flares by 61%-80% compared with colchicine. Canakinumab also reduced the overall rate of flares by 48%-75% relative to colchicine.

Phase III studies are underway, and Novartis plans to file for marketing approval of canakinumab for the treatment and prevention of acute gout attacks by year's end. The monoclonal antibody is licensed as Ilaris for treatment of cryopyrin-associated periodic syndromes.

Dr. Fernando Perez-Ruiz presented a phase II study of RDEA594, a uricosuric drug that normalizes gout patients' underexcretion of uric acid by a novel mechanism: inhibition of reabsorption of uric acid in the proximal tubule of the kidney.

The study involved 123 hyperuricemic gout patients randomized to 4 weeks of RDEA594 at 200, 400, or 600 mg/day or placebo. All were on colchicine at 0.5-0.6 mg/day to reduce the rate of gout flares.

The primary end point — reduction of serum uric acid to less than 6 mg/dL after 4 weeks of treatment — was achieved in 45% of patients on the highest dose of RDEA594 and 0% of those on placebo. The median reduction in serum uric acid in patients on the highest dose was 38%, versus a 1% increase in the placebo arm.

Among the subset of patients with a baseline serum uric level below 10 mg/dL, as is the case for a large majority of gout patients seen in clinical practice, the response rate to the highest dose of RDEA594 was 58%. The side effect profile of RDEA594 was comparable to placebo, added Dr. Perez-Ruiz of Hospital de Cruces in Vizcaya, Spain.

Ardea Biosciences, San Diego, which is developing RDEA594, has not decided whether to take the drug into phase III trials as monotherapy or in combination with febuxostat, with which RDEA594 has shown synergistic effects, a company official said in an interview with

Disclosures: Dr. Schlesinger has received research grants from Brownwood Acres and Novartis. Dr. Kitt is employed by Nuon Therapeutics Inc. Dr. Perez-Ruiz is a consultant to Ardea Biosciences.

As a result of its anti-inflammatory effect, cherry juice concentrate halves levels of interleukin-1-beta and TNF-alpha.

Source DR. SCHLESINGER

ROME — Last year's approval of febuxostat as the first new gout medication in over 40 years appears to have triggered a sharp uptick in drug development for a disease many physicians consider long neglected. The recent approval of pegoticase is proof of the pudding.

Novel gout therapies in the developmental pipeline range from the high tech — a fully human monoclonal antibody to interleukin-1beta — to the low tech, as in cherry juice.

“I've got more than 100 gout patients in my practice on cherry juice concentrate,” Dr. Naomi Schlesinger said in an interview with

Her small retrospective study showed that consumption of 1 tablespoon of Brownwood Acres tart cherry juice concentrate twice daily — equivalent to eating 90-120 cherries — led to a 50% or greater reduction in acute gout attacks in 92% of treated patients, with no side effects. Prophylaxis with cherry juice concentrate is worth considering as an adjunct to urate-lowering therapy, said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at Robert Wood Johnson Medical School, New Brunswick, N.J.

Many patients over the years had told her they loved to eat cherries and thought they might be helpful. Eventually she came across a small 1950 study suggesting a preventive effect.

“I've looked at pomegranate juice, too. It didn't work,” she added.

The mechanism of benefit for cherry juice concentrate is an anti-inflammatory effect, the rheumatologist said. Her in vitro studies showed that cherry juice concentrate reduced by up to half interleukin-1-beta and tumor necrosis factor-alpha secretion by monocytes exposed to monosodium urate crystals.

In gout patients, cherry juice concentrate didn't lower serum urate levels; indeed, more than one-third of patients not on urate-lowering therapy who had averaged close to one attack per month remained attack free during 4-6 months on cherry juice concentrate despite an average serum urate level of 7.8 mg/dL.

Other novel gout therapies subjected to studies presented at the European congress included the anti-interleukin-1-beta monoclonal antibody canakinumab, a uricosuric drug known for now as RDEA594, and tranilast, which has been licensed in Japan for several decades as an oral mast cell inhibitor for treatment of asthma and allergic rhinitis.

Tranilast also has a potent serum uric acid—lowering effect, making it a potential therapy for chronic management of hyperuricemia in gout patients — one that already has a well-established track record for safety, according to Dr. Michael Kitt, executive vice president and chief medical officer at Nuon Therapeutics Inc., San Mateo, Calif.

He presented a preliminary study in which 49 healthy subjects who received 7 days of tranilast at 300, 600, or 900 mg daily showed dose-dependent 1.1- to 3.3- mg/dL reductions in serum uric acid. A phase-IIa study in hyperuricemic patients should be completed in time for presentation later this year at the American College of Rheumatology meeting, and a phase IIb study of tranilast plus allopurinol is just starting in gout patients. When commercialized, tranilast will be combined with allopurinol in a single tablet, Dr. Kitt said in an interview.

Dr. Schlesinger also presented a large phase II clinical trial in which canakinumab, the fully human anti-interleukin-1-beta monoclonal antibody, outperformed colchicine for the reduction of flares in gout patients starting allopurinol therapy.

The double-blind, multicenter, 24-week study included 432 gout patients starting allopurinol who were randomized to 16 weeks of colchicine at 0.5 mg/day, a single subcutaneous injection of canakinumab at 25, 50, 100, 200, or 300 mg, or monthly canakinumab injections at 50, 50, 25, and 25 mg.

The canakinumab regimens reduced the risk of one or more urate-lowering therapy-induced flares by 61%-80% compared with colchicine. Canakinumab also reduced the overall rate of flares by 48%-75% relative to colchicine.

Phase III studies are underway, and Novartis plans to file for marketing approval of canakinumab for the treatment and prevention of acute gout attacks by year's end. The monoclonal antibody is licensed as Ilaris for treatment of cryopyrin-associated periodic syndromes.

Dr. Fernando Perez-Ruiz presented a phase II study of RDEA594, a uricosuric drug that normalizes gout patients' underexcretion of uric acid by a novel mechanism: inhibition of reabsorption of uric acid in the proximal tubule of the kidney.

The study involved 123 hyperuricemic gout patients randomized to 4 weeks of RDEA594 at 200, 400, or 600 mg/day or placebo. All were on colchicine at 0.5-0.6 mg/day to reduce the rate of gout flares.

The primary end point — reduction of serum uric acid to less than 6 mg/dL after 4 weeks of treatment — was achieved in 45% of patients on the highest dose of RDEA594 and 0% of those on placebo. The median reduction in serum uric acid in patients on the highest dose was 38%, versus a 1% increase in the placebo arm.

Among the subset of patients with a baseline serum uric level below 10 mg/dL, as is the case for a large majority of gout patients seen in clinical practice, the response rate to the highest dose of RDEA594 was 58%. The side effect profile of RDEA594 was comparable to placebo, added Dr. Perez-Ruiz of Hospital de Cruces in Vizcaya, Spain.

Ardea Biosciences, San Diego, which is developing RDEA594, has not decided whether to take the drug into phase III trials as monotherapy or in combination with febuxostat, with which RDEA594 has shown synergistic effects, a company official said in an interview with

Disclosures: Dr. Schlesinger has received research grants from Brownwood Acres and Novartis. Dr. Kitt is employed by Nuon Therapeutics Inc. Dr. Perez-Ruiz is a consultant to Ardea Biosciences.

As a result of its anti-inflammatory effect, cherry juice concentrate halves levels of interleukin-1-beta and TNF-alpha.

Source DR. SCHLESINGER

VAIL, COLO. — Fever and limp that do not resolve within 2-3 days deserve further work-up.

Rather than transient synovitis of the hip, an acute self-limited condition that is the single most common cause of fever accompanied by limp in a child, the cause of the symptoms might be septic arthritis due to Kingella kingae, especially in a 1- to 3-year-old child.

However, many of the other disorders in the differential diagnosis of fever plus limp represent medical and surgical emergencies.

These include septic arthritis, osteomyelitis, pyomyositis, and Kawasaki disease, Dr. Samuel R. Dominguez said at the conference, which was sponsored by the Children's Hospital, Denver.

Another possible diagnosis is pyomyositis, noted Dr. Dominguez, a pediatric infectious diseases specialist at the hospital and the University of Colorado at Denver.

Transient Synovitis

The typical age of onset is 3-8 years, boys are affected twice as often as girls, and the etiology is unknown. Because transient synovitis — sometimes called reactive arthritis — is a diagnosis of exclusion and there is considerable symptomatic overlap with septic arthritis, management algorithms call for watchful waitingain a child who has only a low-grade fever, can walk, and doesn't seem too systemically ill.

If there is no improvement in the first 2-3 days, however, it's worthwhile to order measurement of inflammatory markers. A C-reactive protein (CRP) level of 1.2 mg/dL or greater and/or an erythrocyte sedimentation rate (ESR) of at least 30 mm/hr warrants further work-up, including hip ultrasound and aspiration, in order to exclude joint or bone infection, Dr. Dominguez said.

K. kingae in Septic Arthritis

The causative organisms in septic arthritis vary with age. Although Staphylococcus aureus is the most common organism a French study of 131 childrenwhdmitted with a joint or bone infection showed that K. kingae was by far the most common etiologic agent in the 1- to 2-year-old age group. Many of these youngsters were culture negative but polymerase chain reaction positive for Kingella (Pediatr. Infect. Dis. J. 2007;26:377-81).

The take-home message is to consider the possibility of Kingella as a cause of joint or bone infection in 1- to 2-year-olds, and to cover for that with penicillins or cephalosporins, Dr. Dominguez said.

Israeli physicians conducted a retrospective national survey of all clinical microbiologic laboratories in their country, and turned up 322 pediatric K. kingae infections, more than half of which were skeletal.

Overall, 96% of affected children were younger than age 3 years. Most appeared to be only mildly ill. Nearly a quarter had no fever, a third had a nonelevated ESR, and 22% had a normal CRP (Pediatr. Infect. Dis. J. 2010;29:639-43).

Pyomyositis

The annual case count more than doubled during 2000-2006 at Texas Children's Hospital in Houston. The Texpital's reportconsthe largestcase series of bacterial myositis in previously healthy children ever reported from a nontropical region (Clin. Infect. Dis. 2006;43:953-60). The mean ESR was 62 mm/hr, the mean CRP was 16.3 mg/dL, and creatinine kinase levels were normal in all patients.

Pyomyositis is associated with a remarkable degree of pain, and hospital stays for these patients are often longer than with other musculoskeletal infections. Antibiotic therapy typically lasts for 3-4 weeks, including close to 2 weeks ofiIV therapy. Surgical drainage is often required. MRI is the diagnostic imaging of choice. Theexurging incidence of pyomyositis since 2000 is thought tolie due to the rise of methicillin-resistant S. aureus.

Kawasaki Disease

In a series of 198 children with Kawasaki disease reported by the Pediatric Heart Network investigators, 15% had joint pain during the 10 days prior to diagnosis (J. Pediatr. 2009;154:592-5).

Disclosures: Dr. Dominguez said he has no relevant disclosures.

VAIL, COLO. — Fever and limp that do not resolve within 2-3 days deserve further work-up.

Rather than transient synovitis of the hip, an acute self-limited condition that is the single most common cause of fever accompanied by limp in a child, the cause of the symptoms might be septic arthritis due to Kingella kingae, especially in a 1- to 3-year-old child.

However, many of the other disorders in the differential diagnosis of fever plus limp represent medical and surgical emergencies.

These include septic arthritis, osteomyelitis, pyomyositis, and Kawasaki disease, Dr. Samuel R. Dominguez said at the conference, which was sponsored by the Children's Hospital, Denver.

Another possible diagnosis is pyomyositis, noted Dr. Dominguez, a pediatric infectious diseases specialist at the hospital and the University of Colorado at Denver.

Transient Synovitis

The typical age of onset is 3-8 years, boys are affected twice as often as girls, and the etiology is unknown. Because transient synovitis — sometimes called reactive arthritis — is a diagnosis of exclusion and there is considerable symptomatic overlap with septic arthritis, management algorithms call for watchful waitingain a child who has only a low-grade fever, can walk, and doesn't seem too systemically ill.

If there is no improvement in the first 2-3 days, however, it's worthwhile to order measurement of inflammatory markers. A C-reactive protein (CRP) level of 1.2 mg/dL or greater and/or an erythrocyte sedimentation rate (ESR) of at least 30 mm/hr warrants further work-up, including hip ultrasound and aspiration, in order to exclude joint or bone infection, Dr. Dominguez said.

K. kingae in Septic Arthritis

The causative organisms in septic arthritis vary with age. Although Staphylococcus aureus is the most common organism a French study of 131 childrenwhdmitted with a joint or bone infection showed that K. kingae was by far the most common etiologic agent in the 1- to 2-year-old age group. Many of these youngsters were culture negative but polymerase chain reaction positive for Kingella (Pediatr. Infect. Dis. J. 2007;26:377-81).

The take-home message is to consider the possibility of Kingella as a cause of joint or bone infection in 1- to 2-year-olds, and to cover for that with penicillins or cephalosporins, Dr. Dominguez said.

Israeli physicians conducted a retrospective national survey of all clinical microbiologic laboratories in their country, and turned up 322 pediatric K. kingae infections, more than half of which were skeletal.

Overall, 96% of affected children were younger than age 3 years. Most appeared to be only mildly ill. Nearly a quarter had no fever, a third had a nonelevated ESR, and 22% had a normal CRP (Pediatr. Infect. Dis. J. 2010;29:639-43).

Pyomyositis

The annual case count more than doubled during 2000-2006 at Texas Children's Hospital in Houston. The Texpital's reportconsthe largestcase series of bacterial myositis in previously healthy children ever reported from a nontropical region (Clin. Infect. Dis. 2006;43:953-60). The mean ESR was 62 mm/hr, the mean CRP was 16.3 mg/dL, and creatinine kinase levels were normal in all patients.

Pyomyositis is associated with a remarkable degree of pain, and hospital stays for these patients are often longer than with other musculoskeletal infections. Antibiotic therapy typically lasts for 3-4 weeks, including close to 2 weeks ofiIV therapy. Surgical drainage is often required. MRI is the diagnostic imaging of choice. Theexurging incidence of pyomyositis since 2000 is thought tolie due to the rise of methicillin-resistant S. aureus.

Kawasaki Disease

In a series of 198 children with Kawasaki disease reported by the Pediatric Heart Network investigators, 15% had joint pain during the 10 days prior to diagnosis (J. Pediatr. 2009;154:592-5).

Disclosures: Dr. Dominguez said he has no relevant disclosures.

VAIL, COLO. — Fever and limp that do not resolve within 2-3 days deserve further work-up.

Rather than transient synovitis of the hip, an acute self-limited condition that is the single most common cause of fever accompanied by limp in a child, the cause of the symptoms might be septic arthritis due to Kingella kingae, especially in a 1- to 3-year-old child.

However, many of the other disorders in the differential diagnosis of fever plus limp represent medical and surgical emergencies.

These include septic arthritis, osteomyelitis, pyomyositis, and Kawasaki disease, Dr. Samuel R. Dominguez said at the conference, which was sponsored by the Children's Hospital, Denver.

Another possible diagnosis is pyomyositis, noted Dr. Dominguez, a pediatric infectious diseases specialist at the hospital and the University of Colorado at Denver.

Transient Synovitis

The typical age of onset is 3-8 years, boys are affected twice as often as girls, and the etiology is unknown. Because transient synovitis — sometimes called reactive arthritis — is a diagnosis of exclusion and there is considerable symptomatic overlap with septic arthritis, management algorithms call for watchful waitingain a child who has only a low-grade fever, can walk, and doesn't seem too systemically ill.

If there is no improvement in the first 2-3 days, however, it's worthwhile to order measurement of inflammatory markers. A C-reactive protein (CRP) level of 1.2 mg/dL or greater and/or an erythrocyte sedimentation rate (ESR) of at least 30 mm/hr warrants further work-up, including hip ultrasound and aspiration, in order to exclude joint or bone infection, Dr. Dominguez said.

K. kingae in Septic Arthritis

The causative organisms in septic arthritis vary with age. Although Staphylococcus aureus is the most common organism a French study of 131 childrenwhdmitted with a joint or bone infection showed that K. kingae was by far the most common etiologic agent in the 1- to 2-year-old age group. Many of these youngsters were culture negative but polymerase chain reaction positive for Kingella (Pediatr. Infect. Dis. J. 2007;26:377-81).

The take-home message is to consider the possibility of Kingella as a cause of joint or bone infection in 1- to 2-year-olds, and to cover for that with penicillins or cephalosporins, Dr. Dominguez said.

Israeli physicians conducted a retrospective national survey of all clinical microbiologic laboratories in their country, and turned up 322 pediatric K. kingae infections, more than half of which were skeletal.

Overall, 96% of affected children were younger than age 3 years. Most appeared to be only mildly ill. Nearly a quarter had no fever, a third had a nonelevated ESR, and 22% had a normal CRP (Pediatr. Infect. Dis. J. 2010;29:639-43).

Pyomyositis

The annual case count more than doubled during 2000-2006 at Texas Children's Hospital in Houston. The Texpital's reportconsthe largestcase series of bacterial myositis in previously healthy children ever reported from a nontropical region (Clin. Infect. Dis. 2006;43:953-60). The mean ESR was 62 mm/hr, the mean CRP was 16.3 mg/dL, and creatinine kinase levels were normal in all patients.

Pyomyositis is associated with a remarkable degree of pain, and hospital stays for these patients are often longer than with other musculoskeletal infections. Antibiotic therapy typically lasts for 3-4 weeks, including close to 2 weeks ofiIV therapy. Surgical drainage is often required. MRI is the diagnostic imaging of choice. Theexurging incidence of pyomyositis since 2000 is thought tolie due to the rise of methicillin-resistant S. aureus.

Kawasaki Disease

In a series of 198 children with Kawasaki disease reported by the Pediatric Heart Network investigators, 15% had joint pain during the 10 days prior to diagnosis (J. Pediatr. 2009;154:592-5).

Disclosures: Dr. Dominguez said he has no relevant disclosures.

STOCKHOLM — The use of fondaparinux as an antithrombotic agent in percutaneous coronary intervention for acute coronary syndromes could get a major boost in clinical practice now that the optimal dose of adjunctive unfractionated heparin has been carefully defined in the large randomized FUTURA/OASIS-8 study.

It's clear from the study that standard-dose unfractionated heparin, not low-dose, is the right way to go for PCI in ACS patients treated with fondaparinux, Dr. Sanjit S. Jolly said at the congress.

Many interventional cardiologists have balked at using fondaparinux, a synthetic factor Xa inhibitor, despite its impressive performance in the earlier Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS-5) trial, in which it halved major bleeding and produced a 17% reduction in mortality compared with enoxaparin (N. Engl. J. Med. 2006;354:1464-76).

The concern among interventionalists has been that catheter thrombosis rates were higher with fondaparinux in OASIS-5. Although adjunctive unfractionated heparin will prevent that problem, the optimal dose of heparin needed to avoid catheter thrombosis and ischemic complications without compromising fondaparinux's low rate of major bleeding has been unclear – until FUTURA/OASIS-8, said Dr. Jolly of McMaster University, Hamilton, Ont.

The Fondaparinux Trial With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA)/OASIS-8 trial was a double-blind, randomized study involving 2,026 patients undergoing PCI within the next 72 hours for high-risk ACS at 179 hospitals in 18 countries. All patients received 2.5 mg of fondaparinux subcutaneously once daily; after entering the catheterization lab, they were randomized to adjunctive standard- or low-dose unfractionated heparin. Standard-dose heparin was defined as 60 U/kg in the event a glycoprotein IIb/IIIa inhibitor was used and 85 U/kg if not, with dosing guided by activated clotting time (ACT). Low-dose heparin was given at 50 U/kg regardless of glycoprotein IIb/IIIa inhibitor therapy, and without ACT measurement.

The primary end point, major or minor bleeding or major vascular access-site complications within 48 hours after PCI, occurred in roughly 5% of both study arms. But there was a nominally significant difference between the two treatment groups in the key secondary end point: periprocedural major bleeding and the 30-day rate of death, MI, or target vessel revascularization. This occurred in 3.9% of the standard-dose unfractionated heparin group, vs. 5.8% of those on low-dose heparin representing a 51% increased risk with low-dose therapy.

The risk of major bleeding within 48 hours was 1.1% in the standard-dose unfractionated heparin arm and 1.2% with low-dose heparin in FUTURA/OASIS-8, vs. 3.6% with enoxaparin in OASIS-5, he noted.

“FUTURA/OASIS-8 will definitely improve uptake in the community and amongst interventional cardiologists,” he said.

Dr. Ralph Brindis, American College of Cardiology president, agreed.

“This could be a paradigm change,” he predicted in an interview.

“We have been very leery, at least in the United States, in utilizing fondaparinux in ACS patients we're going to take to the cath lab, despite the incredible benefits shown in OASIS-5. … But they've shown in FUTURA/OASIS-8 that you can do so safely and effectively. I think this is going to be very helpful in the cath lab,” added Dr. Brindis, an interventional cardiologist and senior advisor for cardiovascular disease at Northern California Kaiser Permanente in Oakland.

Simultaneously with the Stockholm presentation, the study results were published online (JAMA 2010 Aug. 31 [doi:10.1001/jama.2010.1320

Disclosures: Dr. Jolly received honoraria and research grants from GlaxoSmithKline, the trial sponsor. Dr. Brindis said he had no financial conflicts.

STOCKHOLM — The use of fondaparinux as an antithrombotic agent in percutaneous coronary intervention for acute coronary syndromes could get a major boost in clinical practice now that the optimal dose of adjunctive unfractionated heparin has been carefully defined in the large randomized FUTURA/OASIS-8 study.

It's clear from the study that standard-dose unfractionated heparin, not low-dose, is the right way to go for PCI in ACS patients treated with fondaparinux, Dr. Sanjit S. Jolly said at the congress.

Many interventional cardiologists have balked at using fondaparinux, a synthetic factor Xa inhibitor, despite its impressive performance in the earlier Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS-5) trial, in which it halved major bleeding and produced a 17% reduction in mortality compared with enoxaparin (N. Engl. J. Med. 2006;354:1464-76).

The concern among interventionalists has been that catheter thrombosis rates were higher with fondaparinux in OASIS-5. Although adjunctive unfractionated heparin will prevent that problem, the optimal dose of heparin needed to avoid catheter thrombosis and ischemic complications without compromising fondaparinux's low rate of major bleeding has been unclear – until FUTURA/OASIS-8, said Dr. Jolly of McMaster University, Hamilton, Ont.

The Fondaparinux Trial With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA)/OASIS-8 trial was a double-blind, randomized study involving 2,026 patients undergoing PCI within the next 72 hours for high-risk ACS at 179 hospitals in 18 countries. All patients received 2.5 mg of fondaparinux subcutaneously once daily; after entering the catheterization lab, they were randomized to adjunctive standard- or low-dose unfractionated heparin. Standard-dose heparin was defined as 60 U/kg in the event a glycoprotein IIb/IIIa inhibitor was used and 85 U/kg if not, with dosing guided by activated clotting time (ACT). Low-dose heparin was given at 50 U/kg regardless of glycoprotein IIb/IIIa inhibitor therapy, and without ACT measurement.

The primary end point, major or minor bleeding or major vascular access-site complications within 48 hours after PCI, occurred in roughly 5% of both study arms. But there was a nominally significant difference between the two treatment groups in the key secondary end point: periprocedural major bleeding and the 30-day rate of death, MI, or target vessel revascularization. This occurred in 3.9% of the standard-dose unfractionated heparin group, vs. 5.8% of those on low-dose heparin representing a 51% increased risk with low-dose therapy.

The risk of major bleeding within 48 hours was 1.1% in the standard-dose unfractionated heparin arm and 1.2% with low-dose heparin in FUTURA/OASIS-8, vs. 3.6% with enoxaparin in OASIS-5, he noted.

“FUTURA/OASIS-8 will definitely improve uptake in the community and amongst interventional cardiologists,” he said.

Dr. Ralph Brindis, American College of Cardiology president, agreed.

“This could be a paradigm change,” he predicted in an interview.

“We have been very leery, at least in the United States, in utilizing fondaparinux in ACS patients we're going to take to the cath lab, despite the incredible benefits shown in OASIS-5. … But they've shown in FUTURA/OASIS-8 that you can do so safely and effectively. I think this is going to be very helpful in the cath lab,” added Dr. Brindis, an interventional cardiologist and senior advisor for cardiovascular disease at Northern California Kaiser Permanente in Oakland.

Simultaneously with the Stockholm presentation, the study results were published online (JAMA 2010 Aug. 31 [doi:10.1001/jama.2010.1320

Disclosures: Dr. Jolly received honoraria and research grants from GlaxoSmithKline, the trial sponsor. Dr. Brindis said he had no financial conflicts.

STOCKHOLM — The use of fondaparinux as an antithrombotic agent in percutaneous coronary intervention for acute coronary syndromes could get a major boost in clinical practice now that the optimal dose of adjunctive unfractionated heparin has been carefully defined in the large randomized FUTURA/OASIS-8 study.

It's clear from the study that standard-dose unfractionated heparin, not low-dose, is the right way to go for PCI in ACS patients treated with fondaparinux, Dr. Sanjit S. Jolly said at the congress.

Many interventional cardiologists have balked at using fondaparinux, a synthetic factor Xa inhibitor, despite its impressive performance in the earlier Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS-5) trial, in which it halved major bleeding and produced a 17% reduction in mortality compared with enoxaparin (N. Engl. J. Med. 2006;354:1464-76).

The concern among interventionalists has been that catheter thrombosis rates were higher with fondaparinux in OASIS-5. Although adjunctive unfractionated heparin will prevent that problem, the optimal dose of heparin needed to avoid catheter thrombosis and ischemic complications without compromising fondaparinux's low rate of major bleeding has been unclear – until FUTURA/OASIS-8, said Dr. Jolly of McMaster University, Hamilton, Ont.

The Fondaparinux Trial With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA)/OASIS-8 trial was a double-blind, randomized study involving 2,026 patients undergoing PCI within the next 72 hours for high-risk ACS at 179 hospitals in 18 countries. All patients received 2.5 mg of fondaparinux subcutaneously once daily; after entering the catheterization lab, they were randomized to adjunctive standard- or low-dose unfractionated heparin. Standard-dose heparin was defined as 60 U/kg in the event a glycoprotein IIb/IIIa inhibitor was used and 85 U/kg if not, with dosing guided by activated clotting time (ACT). Low-dose heparin was given at 50 U/kg regardless of glycoprotein IIb/IIIa inhibitor therapy, and without ACT measurement.

The primary end point, major or minor bleeding or major vascular access-site complications within 48 hours after PCI, occurred in roughly 5% of both study arms. But there was a nominally significant difference between the two treatment groups in the key secondary end point: periprocedural major bleeding and the 30-day rate of death, MI, or target vessel revascularization. This occurred in 3.9% of the standard-dose unfractionated heparin group, vs. 5.8% of those on low-dose heparin representing a 51% increased risk with low-dose therapy.

The risk of major bleeding within 48 hours was 1.1% in the standard-dose unfractionated heparin arm and 1.2% with low-dose heparin in FUTURA/OASIS-8, vs. 3.6% with enoxaparin in OASIS-5, he noted.

“FUTURA/OASIS-8 will definitely improve uptake in the community and amongst interventional cardiologists,” he said.

Dr. Ralph Brindis, American College of Cardiology president, agreed.

“This could be a paradigm change,” he predicted in an interview.

“We have been very leery, at least in the United States, in utilizing fondaparinux in ACS patients we're going to take to the cath lab, despite the incredible benefits shown in OASIS-5. … But they've shown in FUTURA/OASIS-8 that you can do so safely and effectively. I think this is going to be very helpful in the cath lab,” added Dr. Brindis, an interventional cardiologist and senior advisor for cardiovascular disease at Northern California Kaiser Permanente in Oakland.

Simultaneously with the Stockholm presentation, the study results were published online (JAMA 2010 Aug. 31 [doi:10.1001/jama.2010.1320

Disclosures: Dr. Jolly received honoraria and research grants from GlaxoSmithKline, the trial sponsor. Dr. Brindis said he had no financial conflicts.

Major Finding: The prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH.

Data Source: Prospective, active-control arm Phase III trial involving 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries randomized to enoxaparin (0.5 mg/kg) or 50-70 IU/kg UFH (with a glycoprotein IIb/IIIa inhibitor) or 70-100 IU/kg without.

Disclosures: The study was sponsored by Assistance Publique-Hôpitaux de Paris with the help of a research grant from Sanofi-Aventis. Dr. Montalescot disclosed that he has received consulting and/or lecture fees from Sanofi-Aventis as well as more than a dozen others.

STOCKHOLM — Intravenous enoxaparin outperformed conventional unfractionated heparin for anticoagulation in primary percutaneous coronary intervention for ST-elevation MI in the Phase III randomized ATOLL trial.

“This is the first pure, direct head-to-head comparison between two anticoagulants in primary PCI [percutaneous coronary intervention] with no mixing of drugs at any point. Our data demonstrate that enoxaparin, which is easier to use, reduced all serious ischemic events on top of intense antiplatelet therapy. And there was no price to pay on the safety side for the benefit observed on the ischemic side,” Dr. Gilles Montalescot said in presenting the ATOLL data at the meeting.

The ATOLL (Acute STEMI Treated With Primary Angioplasty and Intravenous Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up) trial included 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries. None of the patients had received any anticoagulant before randomization. Two-thirds of the participants underwent cardiac catheterization using radial artery access.

During randomization, half of the participants received intravenous enoxaparin at 0.5 mg/kg regardless of whether or not they were on a glycoprotein IIb/IIIa inhibitor.

The other half got intravenous unfractionated heparin (UFH) at either 50-70 IU/kg if they received a glycoprotein IIb/IIIa inhibitor, or 70-100 IU/kg if they did not. UFH dosing was adjusted based on activated clotting time (ACT) measurements; enoxaparin dosing was not.

The primary study end point – a 30-day composite of death, procedure failure, complications of myocardial infarction, or non-CABG major bleeding – occurred in 33.7% of the UFH group, compared with 28% on enoxaparin. The resultant 17% relative risk reduction favoring the low-molecular-weight heparin fell just shy of statistical significance, probably because the exceptionally high use of radial artery access.

However, hard ischemic secondary end points were markedly reduced with enoxaparin. For example, the prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH, said Dr. Montalescot, professor of medicine and head of the cardiac care unit at Hôpital Pitié-Salpêtrière, Paris.

Similarly, the classic triple ischemic end point comprised of death, reinfarction, or urgent revascularization was 8.5% in the UFH arm, compared with 5.1% with enoxaparin. The end point of death or complications of MI occurred in 12.4% of the UFH group, compared with 7.8% with enoxaparin, a 37% reduction in risk.

The primary safety end point in ATOLL – in-hospital major bleeding – occurred in 4.5% of patients on UFH and similarly in 4.9% of those on enoxaparin. The combined rate of major bleeding, complications of MI, or death occurred in 15% of the UFH group, compared with 10.2% on enoxaparin, a statistically significant difference.

Many American interventional cardiologists like using UFH because they can monitor ACT and bump up the heparin in the event of a low-flow state after stent deployment. Dr. Montalescot commented that it makes sense to check ACTs in using UFH because the anticoagulation provided by UFH is “totally unpredictable.” But several studies have shown that staying within the ACT targets doesn't have any impact on ischemic event rates.

“Also, enoxaparin's anticoagulant capability is very predictable. It has been measured in many studies, and we get 95% of patients within the target range. So it doesn't make sense, really, to control anticoagulation in the cath lab. We don't have the ability to adjust anticoagulation with enoxaparin, but you'll get almost all your patients to target with the IV injection,” he explained.

American observers were duly impressed.

“Enoxaparin probably merits more attention in the acute care setting than it receives,” hotline session cochair Dr. Clyde Yancy said in an interview.

“[It] hasn't been broadly embraced by the cardiovascular community, but it looks like there are some real clinical advantages. These new data as well as some older data suggest we should pay more attention to enoxaparin than we have,” added Dr. Yancy, immediate past president of the American Heart Association and medical director of the Baylor Heart and Vascular Institute, Dallas.

“Enoxaparin kind of rears its head once again as a superior drug – and this time with no increased bleeding,” commented former American College of Cardiology president Dr. W. Douglas Weaver in an interview.

“To be superior with MI as an end point, that's pretty striking. I'm surprised. It's fascinating. I can't wait to see all the data. This could be practice changing. Enoxaparin is easier to use. People have been unwilling to use it in the cath lab because you just can't measure the extent of anticoagulation. But as Professor Montalescot says, why do you need to measure it if you know that it's perfect? I thought the data were quite impressive,” said Dr. Weaver of the Henry Ford Health System, Detroit.

Disclosures: Dr. Weaver serves on several data safety and monitoring boards, and has received research support from several drug and device makers, including the Medicines Co., Johnson & Johnson, Boehringher Ingelheim, and Schering Plough. Dr. Yancy has no relevant disclosures.

Major Finding: The prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH.

Data Source: Prospective, active-control arm Phase III trial involving 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries randomized to enoxaparin (0.5 mg/kg) or 50-70 IU/kg UFH (with a glycoprotein IIb/IIIa inhibitor) or 70-100 IU/kg without.

Disclosures: The study was sponsored by Assistance Publique-Hôpitaux de Paris with the help of a research grant from Sanofi-Aventis. Dr. Montalescot disclosed that he has received consulting and/or lecture fees from Sanofi-Aventis as well as more than a dozen others.

STOCKHOLM — Intravenous enoxaparin outperformed conventional unfractionated heparin for anticoagulation in primary percutaneous coronary intervention for ST-elevation MI in the Phase III randomized ATOLL trial.

“This is the first pure, direct head-to-head comparison between two anticoagulants in primary PCI [percutaneous coronary intervention] with no mixing of drugs at any point. Our data demonstrate that enoxaparin, which is easier to use, reduced all serious ischemic events on top of intense antiplatelet therapy. And there was no price to pay on the safety side for the benefit observed on the ischemic side,” Dr. Gilles Montalescot said in presenting the ATOLL data at the meeting.

The ATOLL (Acute STEMI Treated With Primary Angioplasty and Intravenous Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up) trial included 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries. None of the patients had received any anticoagulant before randomization. Two-thirds of the participants underwent cardiac catheterization using radial artery access.

During randomization, half of the participants received intravenous enoxaparin at 0.5 mg/kg regardless of whether or not they were on a glycoprotein IIb/IIIa inhibitor.

The other half got intravenous unfractionated heparin (UFH) at either 50-70 IU/kg if they received a glycoprotein IIb/IIIa inhibitor, or 70-100 IU/kg if they did not. UFH dosing was adjusted based on activated clotting time (ACT) measurements; enoxaparin dosing was not.

The primary study end point – a 30-day composite of death, procedure failure, complications of myocardial infarction, or non-CABG major bleeding – occurred in 33.7% of the UFH group, compared with 28% on enoxaparin. The resultant 17% relative risk reduction favoring the low-molecular-weight heparin fell just shy of statistical significance, probably because the exceptionally high use of radial artery access.

However, hard ischemic secondary end points were markedly reduced with enoxaparin. For example, the prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH, said Dr. Montalescot, professor of medicine and head of the cardiac care unit at Hôpital Pitié-Salpêtrière, Paris.

Similarly, the classic triple ischemic end point comprised of death, reinfarction, or urgent revascularization was 8.5% in the UFH arm, compared with 5.1% with enoxaparin. The end point of death or complications of MI occurred in 12.4% of the UFH group, compared with 7.8% with enoxaparin, a 37% reduction in risk.

The primary safety end point in ATOLL – in-hospital major bleeding – occurred in 4.5% of patients on UFH and similarly in 4.9% of those on enoxaparin. The combined rate of major bleeding, complications of MI, or death occurred in 15% of the UFH group, compared with 10.2% on enoxaparin, a statistically significant difference.

Many American interventional cardiologists like using UFH because they can monitor ACT and bump up the heparin in the event of a low-flow state after stent deployment. Dr. Montalescot commented that it makes sense to check ACTs in using UFH because the anticoagulation provided by UFH is “totally unpredictable.” But several studies have shown that staying within the ACT targets doesn't have any impact on ischemic event rates.

“Also, enoxaparin's anticoagulant capability is very predictable. It has been measured in many studies, and we get 95% of patients within the target range. So it doesn't make sense, really, to control anticoagulation in the cath lab. We don't have the ability to adjust anticoagulation with enoxaparin, but you'll get almost all your patients to target with the IV injection,” he explained.

American observers were duly impressed.

“Enoxaparin probably merits more attention in the acute care setting than it receives,” hotline session cochair Dr. Clyde Yancy said in an interview.

“[It] hasn't been broadly embraced by the cardiovascular community, but it looks like there are some real clinical advantages. These new data as well as some older data suggest we should pay more attention to enoxaparin than we have,” added Dr. Yancy, immediate past president of the American Heart Association and medical director of the Baylor Heart and Vascular Institute, Dallas.

“Enoxaparin kind of rears its head once again as a superior drug – and this time with no increased bleeding,” commented former American College of Cardiology president Dr. W. Douglas Weaver in an interview.

“To be superior with MI as an end point, that's pretty striking. I'm surprised. It's fascinating. I can't wait to see all the data. This could be practice changing. Enoxaparin is easier to use. People have been unwilling to use it in the cath lab because you just can't measure the extent of anticoagulation. But as Professor Montalescot says, why do you need to measure it if you know that it's perfect? I thought the data were quite impressive,” said Dr. Weaver of the Henry Ford Health System, Detroit.

Disclosures: Dr. Weaver serves on several data safety and monitoring boards, and has received research support from several drug and device makers, including the Medicines Co., Johnson & Johnson, Boehringher Ingelheim, and Schering Plough. Dr. Yancy has no relevant disclosures.

Major Finding: The prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH.

Data Source: Prospective, active-control arm Phase III trial involving 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries randomized to enoxaparin (0.5 mg/kg) or 50-70 IU/kg UFH (with a glycoprotein IIb/IIIa inhibitor) or 70-100 IU/kg without.

Disclosures: The study was sponsored by Assistance Publique-Hôpitaux de Paris with the help of a research grant from Sanofi-Aventis. Dr. Montalescot disclosed that he has received consulting and/or lecture fees from Sanofi-Aventis as well as more than a dozen others.

STOCKHOLM — Intravenous enoxaparin outperformed conventional unfractionated heparin for anticoagulation in primary percutaneous coronary intervention for ST-elevation MI in the Phase III randomized ATOLL trial.

“This is the first pure, direct head-to-head comparison between two anticoagulants in primary PCI [percutaneous coronary intervention] with no mixing of drugs at any point. Our data demonstrate that enoxaparin, which is easier to use, reduced all serious ischemic events on top of intense antiplatelet therapy. And there was no price to pay on the safety side for the benefit observed on the ischemic side,” Dr. Gilles Montalescot said in presenting the ATOLL data at the meeting.

The ATOLL (Acute STEMI Treated With Primary Angioplasty and Intravenous Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up) trial included 910 STEMI patients undergoing primary PCI at 43 sites in 4 countries. None of the patients had received any anticoagulant before randomization. Two-thirds of the participants underwent cardiac catheterization using radial artery access.

During randomization, half of the participants received intravenous enoxaparin at 0.5 mg/kg regardless of whether or not they were on a glycoprotein IIb/IIIa inhibitor.

The other half got intravenous unfractionated heparin (UFH) at either 50-70 IU/kg if they received a glycoprotein IIb/IIIa inhibitor, or 70-100 IU/kg if they did not. UFH dosing was adjusted based on activated clotting time (ACT) measurements; enoxaparin dosing was not.

The primary study end point – a 30-day composite of death, procedure failure, complications of myocardial infarction, or non-CABG major bleeding – occurred in 33.7% of the UFH group, compared with 28% on enoxaparin. The resultant 17% relative risk reduction favoring the low-molecular-weight heparin fell just shy of statistical significance, probably because the exceptionally high use of radial artery access.

However, hard ischemic secondary end points were markedly reduced with enoxaparin. For example, the prespecified chief secondary end point consisting of the 30-day rate of death, recurrent MI or acute coronary syndrome, or urgent revascularization was reduced by 41% in the enoxaparin arm to 6.7%, compared with 11.3% with UFH, said Dr. Montalescot, professor of medicine and head of the cardiac care unit at Hôpital Pitié-Salpêtrière, Paris.

Similarly, the classic triple ischemic end point comprised of death, reinfarction, or urgent revascularization was 8.5% in the UFH arm, compared with 5.1% with enoxaparin. The end point of death or complications of MI occurred in 12.4% of the UFH group, compared with 7.8% with enoxaparin, a 37% reduction in risk.

The primary safety end point in ATOLL – in-hospital major bleeding – occurred in 4.5% of patients on UFH and similarly in 4.9% of those on enoxaparin. The combined rate of major bleeding, complications of MI, or death occurred in 15% of the UFH group, compared with 10.2% on enoxaparin, a statistically significant difference.

Many American interventional cardiologists like using UFH because they can monitor ACT and bump up the heparin in the event of a low-flow state after stent deployment. Dr. Montalescot commented that it makes sense to check ACTs in using UFH because the anticoagulation provided by UFH is “totally unpredictable.” But several studies have shown that staying within the ACT targets doesn't have any impact on ischemic event rates.

“Also, enoxaparin's anticoagulant capability is very predictable. It has been measured in many studies, and we get 95% of patients within the target range. So it doesn't make sense, really, to control anticoagulation in the cath lab. We don't have the ability to adjust anticoagulation with enoxaparin, but you'll get almost all your patients to target with the IV injection,” he explained.

American observers were duly impressed.

“Enoxaparin probably merits more attention in the acute care setting than it receives,” hotline session cochair Dr. Clyde Yancy said in an interview.

“[It] hasn't been broadly embraced by the cardiovascular community, but it looks like there are some real clinical advantages. These new data as well as some older data suggest we should pay more attention to enoxaparin than we have,” added Dr. Yancy, immediate past president of the American Heart Association and medical director of the Baylor Heart and Vascular Institute, Dallas.

“Enoxaparin kind of rears its head once again as a superior drug – and this time with no increased bleeding,” commented former American College of Cardiology president Dr. W. Douglas Weaver in an interview.

“To be superior with MI as an end point, that's pretty striking. I'm surprised. It's fascinating. I can't wait to see all the data. This could be practice changing. Enoxaparin is easier to use. People have been unwilling to use it in the cath lab because you just can't measure the extent of anticoagulation. But as Professor Montalescot says, why do you need to measure it if you know that it's perfect? I thought the data were quite impressive,” said Dr. Weaver of the Henry Ford Health System, Detroit.

Disclosures: Dr. Weaver serves on several data safety and monitoring boards, and has received research support from several drug and device makers, including the Medicines Co., Johnson & Johnson, Boehringher Ingelheim, and Schering Plough. Dr. Yancy has no relevant disclosures.

VAIL, COLO. — The emergence of hepatitis B vaccine escape mutant viral strains poses a possible serious threat to the success of the global hepatitis B control program of the World Health Organization, although thus far the danger remains theoretical, according to Dr. Myron J. Levin.

“I think this is a potential crisis for us to keep track of,” Dr. Levin explained at the conference, sponsored by the Children's Hospital, Denver.

Hepatitis B vaccine escape mutants (VEMs) are already here, and there is considerable selection pressure for the formation of more.

Under the wrong conditions, they are capable of causing breakthrough hepatitis B infection in fully immunized individuals.

VEMs occur most often in countries with high rates of endemic hepatitis B infection and universal hepatitis B vaccine immunization programs, such as Taiwan.

A recent report indicates that in the pre–vaccine era, 7.8% of Taiwanese patients with hepatitis B possessed mutant strains not recognized by the vaccine (Antivir. Ther. 2010;15:463–9).

Fifteen years after introduction of universal infant immunization in that country, the prevalence of VEMs among individuals with hepatitis B disease was close to 25%.

On a more positive note, while the prevalence of VEMs has indeed grown, the pool of Taiwanese with serious hepatitis B infection has shrunk markedly. Indeed, the rate of seropositivity to hepatitis B surface antigen (HBsAg) among Taiwanese children has decreased by 95% since the vaccine program was introduced. Liver cancer in this population has been reduced by 60%.

“So the implication is right now there is no obvious problem. But it's something we need to monitor,” observed Dr. Levin, professor of pediatrics and medicine at the University of Colorado, Denver.

Worst case scenario? The vaccines would have to be redesigned to recognize VEMs and incorporate hepatitis B virus proteins that aren't vulnerable to escape mutations, he added.

Selection pressure for formation of VEMs comes from two distinct sources: immunization and lamivudine monotherapy for chronic hepatitis B.

The hepatitis B virus is a DNA virus that utilizes a reverse transcriptase enzyme to replicate its viral genome, as does HIV. Reverse transcription is a notoriously error-prone process that can lead to single–amino acid mutations in HBsAg. The antibodies drawn forth by the hepatitis B vaccine specifically target the surface antigen protein. If the surface antigen protein contains a mutation, the vaccine may be unable to neutralize the virus, and a VEM is created.

Moreover, depending upon the epitopes mutated in a VEM, the VEM may not be detected by tests for HBsAg. “You could have someone with chronic hepatitis B and you wouldn't detect it,” according to Dr. Levin.

Thus, even as the global hepatitis B immunization program continues to reduce new cases of hepatitis B infection and the enormous burden of chronic hepatitis B disease, it is simultaneously generating VEMs, thereby potentially sewing the seeds of the program's failure.

A second, entirely separate source of selection pressure promoting the creation of VEMs stems from the fact that lamivudine frequently leads to mutations in the gene for reverse transcriptase, which happens to overlap the surface antigen gene. These mutations can result in changes in the surface antigen protein, which under the wrong conditions will result in VEMs.

“The outcome will depend on whether the new mutant is stable, whether it can cause antigenic change in the neutralization characteristics of the surface antigen, whether it's transmissible from one person to another, and whether it can cause acute or chronic disease. But if all these things line up right, treatment with lamivudine could create a situation where you have more VEMs,” Dr. Levin continued.

Lamivudine was the first nucleoside analog approved for the treatment of chronic hepatitis B infection. It remains widely used as monotherapy in many resource-poor countries because it is inexpensive, relatively free of side effects, and effective – at least initially. As has been seen with single-agent therapy in HIV and tuberculosis, however, lamivudine monotherapy eventually results in the appearance of lamivudine-resistant hepatitis B strains.

The World Health Organization is monitoring the hepatitis B VEM situation closely (Bull. World Health Org. 2010;88:66–73). http://www.ncbi.nlm.nih.gov/sites

Dr. Levin disclosed that he has served as a consultant to Merck & Co. and GlaxoSmithKline. Both companies make hepatitis A and B vaccines.

VAIL, COLO. — The emergence of hepatitis B vaccine escape mutant viral strains poses a possible serious threat to the success of the global hepatitis B control program of the World Health Organization, although thus far the danger remains theoretical, according to Dr. Myron J. Levin.

“I think this is a potential crisis for us to keep track of,” Dr. Levin explained at the conference, sponsored by the Children's Hospital, Denver.

Hepatitis B vaccine escape mutants (VEMs) are already here, and there is considerable selection pressure for the formation of more.

Under the wrong conditions, they are capable of causing breakthrough hepatitis B infection in fully immunized individuals.

VEMs occur most often in countries with high rates of endemic hepatitis B infection and universal hepatitis B vaccine immunization programs, such as Taiwan.

A recent report indicates that in the pre–vaccine era, 7.8% of Taiwanese patients with hepatitis B possessed mutant strains not recognized by the vaccine (Antivir. Ther. 2010;15:463–9).

Fifteen years after introduction of universal infant immunization in that country, the prevalence of VEMs among individuals with hepatitis B disease was close to 25%.

On a more positive note, while the prevalence of VEMs has indeed grown, the pool of Taiwanese with serious hepatitis B infection has shrunk markedly. Indeed, the rate of seropositivity to hepatitis B surface antigen (HBsAg) among Taiwanese children has decreased by 95% since the vaccine program was introduced. Liver cancer in this population has been reduced by 60%.

“So the implication is right now there is no obvious problem. But it's something we need to monitor,” observed Dr. Levin, professor of pediatrics and medicine at the University of Colorado, Denver.

Worst case scenario? The vaccines would have to be redesigned to recognize VEMs and incorporate hepatitis B virus proteins that aren't vulnerable to escape mutations, he added.

Selection pressure for formation of VEMs comes from two distinct sources: immunization and lamivudine monotherapy for chronic hepatitis B.

The hepatitis B virus is a DNA virus that utilizes a reverse transcriptase enzyme to replicate its viral genome, as does HIV. Reverse transcription is a notoriously error-prone process that can lead to single–amino acid mutations in HBsAg. The antibodies drawn forth by the hepatitis B vaccine specifically target the surface antigen protein. If the surface antigen protein contains a mutation, the vaccine may be unable to neutralize the virus, and a VEM is created.

Moreover, depending upon the epitopes mutated in a VEM, the VEM may not be detected by tests for HBsAg. “You could have someone with chronic hepatitis B and you wouldn't detect it,” according to Dr. Levin.

Thus, even as the global hepatitis B immunization program continues to reduce new cases of hepatitis B infection and the enormous burden of chronic hepatitis B disease, it is simultaneously generating VEMs, thereby potentially sewing the seeds of the program's failure.

A second, entirely separate source of selection pressure promoting the creation of VEMs stems from the fact that lamivudine frequently leads to mutations in the gene for reverse transcriptase, which happens to overlap the surface antigen gene. These mutations can result in changes in the surface antigen protein, which under the wrong conditions will result in VEMs.

“The outcome will depend on whether the new mutant is stable, whether it can cause antigenic change in the neutralization characteristics of the surface antigen, whether it's transmissible from one person to another, and whether it can cause acute or chronic disease. But if all these things line up right, treatment with lamivudine could create a situation where you have more VEMs,” Dr. Levin continued.

Lamivudine was the first nucleoside analog approved for the treatment of chronic hepatitis B infection. It remains widely used as monotherapy in many resource-poor countries because it is inexpensive, relatively free of side effects, and effective – at least initially. As has been seen with single-agent therapy in HIV and tuberculosis, however, lamivudine monotherapy eventually results in the appearance of lamivudine-resistant hepatitis B strains.

The World Health Organization is monitoring the hepatitis B VEM situation closely (Bull. World Health Org. 2010;88:66–73). http://www.ncbi.nlm.nih.gov/sites

Dr. Levin disclosed that he has served as a consultant to Merck & Co. and GlaxoSmithKline. Both companies make hepatitis A and B vaccines.

VAIL, COLO. — The emergence of hepatitis B vaccine escape mutant viral strains poses a possible serious threat to the success of the global hepatitis B control program of the World Health Organization, although thus far the danger remains theoretical, according to Dr. Myron J. Levin.

“I think this is a potential crisis for us to keep track of,” Dr. Levin explained at the conference, sponsored by the Children's Hospital, Denver.

Hepatitis B vaccine escape mutants (VEMs) are already here, and there is considerable selection pressure for the formation of more.

Under the wrong conditions, they are capable of causing breakthrough hepatitis B infection in fully immunized individuals.

VEMs occur most often in countries with high rates of endemic hepatitis B infection and universal hepatitis B vaccine immunization programs, such as Taiwan.

A recent report indicates that in the pre–vaccine era, 7.8% of Taiwanese patients with hepatitis B possessed mutant strains not recognized by the vaccine (Antivir. Ther. 2010;15:463–9).

Fifteen years after introduction of universal infant immunization in that country, the prevalence of VEMs among individuals with hepatitis B disease was close to 25%.

On a more positive note, while the prevalence of VEMs has indeed grown, the pool of Taiwanese with serious hepatitis B infection has shrunk markedly. Indeed, the rate of seropositivity to hepatitis B surface antigen (HBsAg) among Taiwanese children has decreased by 95% since the vaccine program was introduced. Liver cancer in this population has been reduced by 60%.

“So the implication is right now there is no obvious problem. But it's something we need to monitor,” observed Dr. Levin, professor of pediatrics and medicine at the University of Colorado, Denver.

Worst case scenario? The vaccines would have to be redesigned to recognize VEMs and incorporate hepatitis B virus proteins that aren't vulnerable to escape mutations, he added.

Selection pressure for formation of VEMs comes from two distinct sources: immunization and lamivudine monotherapy for chronic hepatitis B.

The hepatitis B virus is a DNA virus that utilizes a reverse transcriptase enzyme to replicate its viral genome, as does HIV. Reverse transcription is a notoriously error-prone process that can lead to single–amino acid mutations in HBsAg. The antibodies drawn forth by the hepatitis B vaccine specifically target the surface antigen protein. If the surface antigen protein contains a mutation, the vaccine may be unable to neutralize the virus, and a VEM is created.

Moreover, depending upon the epitopes mutated in a VEM, the VEM may not be detected by tests for HBsAg. “You could have someone with chronic hepatitis B and you wouldn't detect it,” according to Dr. Levin.

Thus, even as the global hepatitis B immunization program continues to reduce new cases of hepatitis B infection and the enormous burden of chronic hepatitis B disease, it is simultaneously generating VEMs, thereby potentially sewing the seeds of the program's failure.

A second, entirely separate source of selection pressure promoting the creation of VEMs stems from the fact that lamivudine frequently leads to mutations in the gene for reverse transcriptase, which happens to overlap the surface antigen gene. These mutations can result in changes in the surface antigen protein, which under the wrong conditions will result in VEMs.

“The outcome will depend on whether the new mutant is stable, whether it can cause antigenic change in the neutralization characteristics of the surface antigen, whether it's transmissible from one person to another, and whether it can cause acute or chronic disease. But if all these things line up right, treatment with lamivudine could create a situation where you have more VEMs,” Dr. Levin continued.

Lamivudine was the first nucleoside analog approved for the treatment of chronic hepatitis B infection. It remains widely used as monotherapy in many resource-poor countries because it is inexpensive, relatively free of side effects, and effective – at least initially. As has been seen with single-agent therapy in HIV and tuberculosis, however, lamivudine monotherapy eventually results in the appearance of lamivudine-resistant hepatitis B strains.

The World Health Organization is monitoring the hepatitis B VEM situation closely (Bull. World Health Org. 2010;88:66–73). http://www.ncbi.nlm.nih.gov/sites

Dr. Levin disclosed that he has served as a consultant to Merck & Co. and GlaxoSmithKline. Both companies make hepatitis A and B vaccines.

VAIL, COLO. — Immunization at birth against hepatitis B protects against symptomatic disease for at least 20 years, despite frequent exposures, according to several recent studies.

Whether newborn immunization provides protection for life without the need for booster doses is still an open question.

Experts continue to monitor the hepatitis B vaccine's long-term effectiveness, and recommendations for booster doses will be issued, should evidence show they are necessary.

But the recent reports suggesting that the duration of protection is 2 decades and counting are quite encouraging, Dr. Myron J. Levin said at the conference, which was sponsored by the Children's Hospital, Denver.

He cited a meta-analysis by investigators at Tehran (Iran) University of Medical Sciences, who included 34 studies with more than 9,300 subjects.

The researchers determined that the rate of breakthrough infection was extremely low: 0% in the first 5 years post vaccination, 0.06% during years 6–10, 0.2% in years 11–15, and 0% in years 16–20 (Vaccine 2010;28:623–31).

Even more encouraging was a study of 204 Thai children who were immunized at birth and born to chronically infected hepatitis B surface antigen–positive mothers.

These children, living in a highly endemic area for hepatitis B, have been followed for 17 years with annual clinic visits and serologic studies.

The frequent transient presence of hepatitis B surface antigen and/or hepatitis B core antibody indicated that these subjects were indeed heavily exposed to hepatitis B virus throughout their childhood and adolescence.

Yet no one with transient hepatitis B surface antigen developed any clinical symptoms of liver disease.

And no cases of chronic hepatitis B occurred in the study population (J. Infect. Dis. 2009;200:33–8). In other words, the vaccine did exactly what it's supposed to do: It prevented clinical disease, observed Dr. Levin, professor of pediatrics and medicine at the University of Colorado, Denver.

A key element in the persistence of protection against clinical hepatitis B in patients who were immunized as children is immune memory.

This was underscored in a study of 493 Alaskan children who had been immunized 22 years earlier, although not at birth. At follow-up, 60% of subjects still had protective levels of vaccine-induced antibody (defined as 10 mIU/mL).

Of the remaining 193 subjects, 160 (83%) demonstrated a rapid rise in antibody level in response to a booster. This early spike in antibody is evidence of immune memory, whereby the immune system is able to kick in and provide the needed protection upon exposure to hepatitis B, even though the level of protective antibody in a vaccinated person declines with time.

If it is assumed that immune memory indicates protection, 93% of subjects in this study were still protected against hepatitis B at 22 years after vaccination. The investigators concluded that booster doses aren't needed (J. Infect. Dis. 2009;200: 1390–6).

Dr. Levin said that regardless of how long it ultimately turns out that protection against hepatitis B persists after childhood vaccination, it's absolutely necessary that physicians do a better job of making sure neonates get a birth dose of vaccine while they're still in the hospital. At present, this occurs in only about one-half of neonates born in the United States. As a result, roughly 8,000 infants per year are chronically infected with hepatitis B.

Dr. Levin disclosed that he has served as a consultant to Merck & Co. and GlaxoSmithKline. Both companies make hepatitis A and B vaccines.

A key element in the persistence of protection in patients immunized as children is immune memory.

Source DR. LEVIN

VAIL, COLO. — Immunization at birth against hepatitis B protects against symptomatic disease for at least 20 years, despite frequent exposures, according to several recent studies.

Whether newborn immunization provides protection for life without the need for booster doses is still an open question.

Experts continue to monitor the hepatitis B vaccine's long-term effectiveness, and recommendations for booster doses will be issued, should evidence show they are necessary.

But the recent reports suggesting that the duration of protection is 2 decades and counting are quite encouraging, Dr. Myron J. Levin said at the conference, which was sponsored by the Children's Hospital, Denver.

He cited a meta-analysis by investigators at Tehran (Iran) University of Medical Sciences, who included 34 studies with more than 9,300 subjects.

The researchers determined that the rate of breakthrough infection was extremely low: 0% in the first 5 years post vaccination, 0.06% during years 6–10, 0.2% in years 11–15, and 0% in years 16–20 (Vaccine 2010;28:623–31).

Even more encouraging was a study of 204 Thai children who were immunized at birth and born to chronically infected hepatitis B surface antigen–positive mothers.

These children, living in a highly endemic area for hepatitis B, have been followed for 17 years with annual clinic visits and serologic studies.

The frequent transient presence of hepatitis B surface antigen and/or hepatitis B core antibody indicated that these subjects were indeed heavily exposed to hepatitis B virus throughout their childhood and adolescence.

Yet no one with transient hepatitis B surface antigen developed any clinical symptoms of liver disease.

And no cases of chronic hepatitis B occurred in the study population (J. Infect. Dis. 2009;200:33–8). In other words, the vaccine did exactly what it's supposed to do: It prevented clinical disease, observed Dr. Levin, professor of pediatrics and medicine at the University of Colorado, Denver.

A key element in the persistence of protection against clinical hepatitis B in patients who were immunized as children is immune memory.

This was underscored in a study of 493 Alaskan children who had been immunized 22 years earlier, although not at birth. At follow-up, 60% of subjects still had protective levels of vaccine-induced antibody (defined as 10 mIU/mL).

Of the remaining 193 subjects, 160 (83%) demonstrated a rapid rise in antibody level in response to a booster. This early spike in antibody is evidence of immune memory, whereby the immune system is able to kick in and provide the needed protection upon exposure to hepatitis B, even though the level of protective antibody in a vaccinated person declines with time.

If it is assumed that immune memory indicates protection, 93% of subjects in this study were still protected against hepatitis B at 22 years after vaccination. The investigators concluded that booster doses aren't needed (J. Infect. Dis. 2009;200: 1390–6).

Dr. Levin said that regardless of how long it ultimately turns out that protection against hepatitis B persists after childhood vaccination, it's absolutely necessary that physicians do a better job of making sure neonates get a birth dose of vaccine while they're still in the hospital. At present, this occurs in only about one-half of neonates born in the United States. As a result, roughly 8,000 infants per year are chronically infected with hepatitis B.

Dr. Levin disclosed that he has served as a consultant to Merck & Co. and GlaxoSmithKline. Both companies make hepatitis A and B vaccines.

A key element in the persistence of protection in patients immunized as children is immune memory.

Source DR. LEVIN

VAIL, COLO. — Immunization at birth against hepatitis B protects against symptomatic disease for at least 20 years, despite frequent exposures, according to several recent studies.

Whether newborn immunization provides protection for life without the need for booster doses is still an open question.

Experts continue to monitor the hepatitis B vaccine's long-term effectiveness, and recommendations for booster doses will be issued, should evidence show they are necessary.

But the recent reports suggesting that the duration of protection is 2 decades and counting are quite encouraging, Dr. Myron J. Levin said at the conference, which was sponsored by the Children's Hospital, Denver.

He cited a meta-analysis by investigators at Tehran (Iran) University of Medical Sciences, who included 34 studies with more than 9,300 subjects.

The researchers determined that the rate of breakthrough infection was extremely low: 0% in the first 5 years post vaccination, 0.06% during years 6–10, 0.2% in years 11–15, and 0% in years 16–20 (Vaccine 2010;28:623–31).

Even more encouraging was a study of 204 Thai children who were immunized at birth and born to chronically infected hepatitis B surface antigen–positive mothers.

These children, living in a highly endemic area for hepatitis B, have been followed for 17 years with annual clinic visits and serologic studies.

The frequent transient presence of hepatitis B surface antigen and/or hepatitis B core antibody indicated that these subjects were indeed heavily exposed to hepatitis B virus throughout their childhood and adolescence.

Yet no one with transient hepatitis B surface antigen developed any clinical symptoms of liver disease.

And no cases of chronic hepatitis B occurred in the study population (J. Infect. Dis. 2009;200:33–8). In other words, the vaccine did exactly what it's supposed to do: It prevented clinical disease, observed Dr. Levin, professor of pediatrics and medicine at the University of Colorado, Denver.

A key element in the persistence of protection against clinical hepatitis B in patients who were immunized as children is immune memory.

This was underscored in a study of 493 Alaskan children who had been immunized 22 years earlier, although not at birth. At follow-up, 60% of subjects still had protective levels of vaccine-induced antibody (defined as 10 mIU/mL).

Of the remaining 193 subjects, 160 (83%) demonstrated a rapid rise in antibody level in response to a booster. This early spike in antibody is evidence of immune memory, whereby the immune system is able to kick in and provide the needed protection upon exposure to hepatitis B, even though the level of protective antibody in a vaccinated person declines with time.

If it is assumed that immune memory indicates protection, 93% of subjects in this study were still protected against hepatitis B at 22 years after vaccination. The investigators concluded that booster doses aren't needed (J. Infect. Dis. 2009;200: 1390–6).

Dr. Levin said that regardless of how long it ultimately turns out that protection against hepatitis B persists after childhood vaccination, it's absolutely necessary that physicians do a better job of making sure neonates get a birth dose of vaccine while they're still in the hospital. At present, this occurs in only about one-half of neonates born in the United States. As a result, roughly 8,000 infants per year are chronically infected with hepatitis B.

Dr. Levin disclosed that he has served as a consultant to Merck & Co. and GlaxoSmithKline. Both companies make hepatitis A and B vaccines.

A key element in the persistence of protection in patients immunized as children is immune memory.

Source DR. LEVIN