Bruce Jancin

STOCKHOLM – Stand-alone angiotensin II receptor blocker therapy proved of no benefit in preventing recurrences of paroxysmal atrial fibrillation in patients without structural heart disease in a large German randomized double-blind trial.

“ARB therapy may not be recommended as first-line treatment for paroxysmal atrial fibrillation if not indicated for other reasons,” Dr. Andreas Goette concluded, in presenting the results of the ANTIPAF trial at the congress.

The ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation) trial involved a total of 425 patients at 37 participating German centers.

All participants had documented paroxysmal atrial fibrillation (PAF) and no or minimal structural heart disease. They were randomized in double-blind fashion to receive olmesartan at 40 mg/day or placebo and followed for 12 months, during which they were not permitted to be on concomitant antiarrhythmic agents, other ARBs, or ACE inhibitors. If they were on a beta-blocker before enrollment, they could stay on it, but starting a beta-blocker after randomization was not allowed.

The primary study end point was total atrial fibrillation burden during 1 year of follow-up, as assessed using a novel tele-ECG technology employed on a daily basis.

Based on an analysis of nearly 88,000 tele-ECGs, it was clear that olmesartan had no impact on total atrial fibrillation burden. Patients on olmesartan had a mean 0.151% of days of atrial fibrillation during follow-up, while those on placebo had 0.147%, reported Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

The two groups did not differ in terms of numerous prespecified secondary end points either, including time to first recurrence of atrial fibrillation, quality of life measures, time to development of persistent atrial fibrillation, and number of hospitalizations.

Atrial fibrillation affects roughly 4% of people in their 60s and up to 20% of those in their 80s. Good-quality animal and cellular data suggest angiotensin II is a major player in atrial fibrillation, figuring prominently in the vicious cycle in which atrial fibrillation begets more frequent and severe atrial fibrillation by promoting atrial remodeling and left ventricular dysfunction, and vice versa.

“From experimental work, it appears very appealing to inhibit the action of angiotensin II to treat atrial fibrillation,” the cardiologist observed.

Early clinical trials suggested that PAF could be suppressed by ARB therapy, particularly when combined with an antiarrhythmic agent. These studies, however, had various weaknesses that left open the question of whether stand-alone ARB therapy is effective in PAF. This was the question the ANTIPAF trial was designed to address.

Dr. Goette said that he sees the tele-ECG monitoring as one of the trial's unique strengths. Patients carried the credit card–sized tele-ECG device around with them during the day and were asked to press a button and hold it to their chest to record an ECG at least once daily. They phoned in the data for storage and analysis.

Unlike Dr. Goette, however, discussant Dr. A. John Camm took a dim view of the tele-ECG–based primary end point.

“The intermittent and noncontinuous monitoring of the heart rhythm is important. Although we heard of the tens of thousands of ECGs that were involved, there are on the order of a thousandfold that number of heart beats, and continuous monitoring might have been much better,” said Dr. Camm of St. George's University of London.

He also took issue with the duration of follow-up in ANTIPAF: “The length of the follow-up is intermediate. For an effect to reverse fibrosis we might need far longer than 1 year.”

Although there are reasonably persuasive clinical trials data indicating ARBs are effective for the primary prevention of atrial fibrillation, ANTIPAF joins several earlier studies in failing to show any benefit for various ARBs in preventing recurrences of PAF, Dr. Camm said.

The ANTIPAF trial was funded by the German Ministry of Research and Education and carried out by the German Competence Network on Atrial Fibrillation.

Dr. Goette said he had no financial conflicts.

Analysis of nearly 88,000 tele-ECGs showed that olmesartan had no impact on total atrial fibrillation burden.

Source DR. GOETTE

STOCKHOLM – Stand-alone angiotensin II receptor blocker therapy proved of no benefit in preventing recurrences of paroxysmal atrial fibrillation in patients without structural heart disease in a large German randomized double-blind trial.

“ARB therapy may not be recommended as first-line treatment for paroxysmal atrial fibrillation if not indicated for other reasons,” Dr. Andreas Goette concluded, in presenting the results of the ANTIPAF trial at the congress.

The ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation) trial involved a total of 425 patients at 37 participating German centers.

All participants had documented paroxysmal atrial fibrillation (PAF) and no or minimal structural heart disease. They were randomized in double-blind fashion to receive olmesartan at 40 mg/day or placebo and followed for 12 months, during which they were not permitted to be on concomitant antiarrhythmic agents, other ARBs, or ACE inhibitors. If they were on a beta-blocker before enrollment, they could stay on it, but starting a beta-blocker after randomization was not allowed.

The primary study end point was total atrial fibrillation burden during 1 year of follow-up, as assessed using a novel tele-ECG technology employed on a daily basis.

Based on an analysis of nearly 88,000 tele-ECGs, it was clear that olmesartan had no impact on total atrial fibrillation burden. Patients on olmesartan had a mean 0.151% of days of atrial fibrillation during follow-up, while those on placebo had 0.147%, reported Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

The two groups did not differ in terms of numerous prespecified secondary end points either, including time to first recurrence of atrial fibrillation, quality of life measures, time to development of persistent atrial fibrillation, and number of hospitalizations.

Atrial fibrillation affects roughly 4% of people in their 60s and up to 20% of those in their 80s. Good-quality animal and cellular data suggest angiotensin II is a major player in atrial fibrillation, figuring prominently in the vicious cycle in which atrial fibrillation begets more frequent and severe atrial fibrillation by promoting atrial remodeling and left ventricular dysfunction, and vice versa.

“From experimental work, it appears very appealing to inhibit the action of angiotensin II to treat atrial fibrillation,” the cardiologist observed.

Early clinical trials suggested that PAF could be suppressed by ARB therapy, particularly when combined with an antiarrhythmic agent. These studies, however, had various weaknesses that left open the question of whether stand-alone ARB therapy is effective in PAF. This was the question the ANTIPAF trial was designed to address.

Dr. Goette said that he sees the tele-ECG monitoring as one of the trial's unique strengths. Patients carried the credit card–sized tele-ECG device around with them during the day and were asked to press a button and hold it to their chest to record an ECG at least once daily. They phoned in the data for storage and analysis.

Unlike Dr. Goette, however, discussant Dr. A. John Camm took a dim view of the tele-ECG–based primary end point.

“The intermittent and noncontinuous monitoring of the heart rhythm is important. Although we heard of the tens of thousands of ECGs that were involved, there are on the order of a thousandfold that number of heart beats, and continuous monitoring might have been much better,” said Dr. Camm of St. George's University of London.

He also took issue with the duration of follow-up in ANTIPAF: “The length of the follow-up is intermediate. For an effect to reverse fibrosis we might need far longer than 1 year.”

Although there are reasonably persuasive clinical trials data indicating ARBs are effective for the primary prevention of atrial fibrillation, ANTIPAF joins several earlier studies in failing to show any benefit for various ARBs in preventing recurrences of PAF, Dr. Camm said.

The ANTIPAF trial was funded by the German Ministry of Research and Education and carried out by the German Competence Network on Atrial Fibrillation.

Dr. Goette said he had no financial conflicts.

Analysis of nearly 88,000 tele-ECGs showed that olmesartan had no impact on total atrial fibrillation burden.

Source DR. GOETTE

STOCKHOLM – Stand-alone angiotensin II receptor blocker therapy proved of no benefit in preventing recurrences of paroxysmal atrial fibrillation in patients without structural heart disease in a large German randomized double-blind trial.

“ARB therapy may not be recommended as first-line treatment for paroxysmal atrial fibrillation if not indicated for other reasons,” Dr. Andreas Goette concluded, in presenting the results of the ANTIPAF trial at the congress.

The ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation) trial involved a total of 425 patients at 37 participating German centers.

All participants had documented paroxysmal atrial fibrillation (PAF) and no or minimal structural heart disease. They were randomized in double-blind fashion to receive olmesartan at 40 mg/day or placebo and followed for 12 months, during which they were not permitted to be on concomitant antiarrhythmic agents, other ARBs, or ACE inhibitors. If they were on a beta-blocker before enrollment, they could stay on it, but starting a beta-blocker after randomization was not allowed.

The primary study end point was total atrial fibrillation burden during 1 year of follow-up, as assessed using a novel tele-ECG technology employed on a daily basis.

Based on an analysis of nearly 88,000 tele-ECGs, it was clear that olmesartan had no impact on total atrial fibrillation burden. Patients on olmesartan had a mean 0.151% of days of atrial fibrillation during follow-up, while those on placebo had 0.147%, reported Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

The two groups did not differ in terms of numerous prespecified secondary end points either, including time to first recurrence of atrial fibrillation, quality of life measures, time to development of persistent atrial fibrillation, and number of hospitalizations.

Atrial fibrillation affects roughly 4% of people in their 60s and up to 20% of those in their 80s. Good-quality animal and cellular data suggest angiotensin II is a major player in atrial fibrillation, figuring prominently in the vicious cycle in which atrial fibrillation begets more frequent and severe atrial fibrillation by promoting atrial remodeling and left ventricular dysfunction, and vice versa.

“From experimental work, it appears very appealing to inhibit the action of angiotensin II to treat atrial fibrillation,” the cardiologist observed.

Early clinical trials suggested that PAF could be suppressed by ARB therapy, particularly when combined with an antiarrhythmic agent. These studies, however, had various weaknesses that left open the question of whether stand-alone ARB therapy is effective in PAF. This was the question the ANTIPAF trial was designed to address.

Dr. Goette said that he sees the tele-ECG monitoring as one of the trial's unique strengths. Patients carried the credit card–sized tele-ECG device around with them during the day and were asked to press a button and hold it to their chest to record an ECG at least once daily. They phoned in the data for storage and analysis.

Unlike Dr. Goette, however, discussant Dr. A. John Camm took a dim view of the tele-ECG–based primary end point.

“The intermittent and noncontinuous monitoring of the heart rhythm is important. Although we heard of the tens of thousands of ECGs that were involved, there are on the order of a thousandfold that number of heart beats, and continuous monitoring might have been much better,” said Dr. Camm of St. George's University of London.

He also took issue with the duration of follow-up in ANTIPAF: “The length of the follow-up is intermediate. For an effect to reverse fibrosis we might need far longer than 1 year.”

Although there are reasonably persuasive clinical trials data indicating ARBs are effective for the primary prevention of atrial fibrillation, ANTIPAF joins several earlier studies in failing to show any benefit for various ARBs in preventing recurrences of PAF, Dr. Camm said.

The ANTIPAF trial was funded by the German Ministry of Research and Education and carried out by the German Competence Network on Atrial Fibrillation.

Dr. Goette said he had no financial conflicts.

Analysis of nearly 88,000 tele-ECGs showed that olmesartan had no impact on total atrial fibrillation burden.

Source DR. GOETTE

KEYSTONE, COLO. – Serum cystatin C isn't ready for prime-time use in clinical practice as an alternative to urinary albumin excretion and serum creatinine in screening for diabetic nephropathy, but the unfolding research on this novel biomarker is definitely worth keeping an eye on.

“From a pediatric diabetes perspective, were we to have more data on cystatin C, it would sure be appealing to be able to collect it from a blood sample and not have to try to get overnight urines or even spot urines. This is a biomarker that may pan out as something useful in the future,” Dr. David M. Maahs said at the conference, sponsored by the Children's Diabetes Foundation at Denver.

Growing evidence suggests serum cystatin C provides a more accurate estimate of glomerular filtration rate (GFR) than do predictive equations based upon serum creatinine, such as the widely used Cockroft-Gault or Modification of Diet in Renal Disease equations.

“Cystatin C has been described as like an HbA_1c for renal function,” observed Dr. Maahs of the Barbara Davis Center for Childhood Diabetes and the University of Colorado, Denver.

Cystatin C also appears to be superior to serum creatinine as a predictor of the risk of death and cardiovascular events in the elderly in general (N. Engl. J. Med. 2005;352:2049-60). Furthermore, in an analysis restricted to 691 elderly diabetics in the Cardiovascular Health Study, cystatin C–based estimated GFR predicted mortality more strongly than did serum creatinine–based estimated GFR (Diabetes Care 2009;32:1833-8).

Moreover, in a study of 509 adults with type 1 diabetes followed for 2.5 years, Dr. Maahs and coworkers showed that serum cystatin C predicted progression of subclinical coronary atherosclerosis as reflected by coronary artery calcification better than serum creatinine, estimated glomerular filtration rate, or albumin excretion rate (Diabetes 2007;56:2774-9).

That being said, data on cystatin C's performance in pediatric populations with diabetes remain lacking, he noted.

Serum cystatin C goes up as the GFR goes down. Cystatin C is thought to better reflect GFR than does serum creatinine because it is independent of age, sex, and muscle mass. Cystatin C is a stable protein produced by nucleated cells at a constant rate. It is freely filtered at the glomerulus because of its small molecular mass, it is not reabsorbed, and it is eliminated by the kidneys.

Putting aside for the future the question of cystatin C as a potential tool for following GFR in diabetic patients, Dr. Maahs stressed the importance of following guidelines for screening for diabetic nephropathy in young patients. About 20%-40% of patients with diabetes develop nephropathy. Indeed, diabetic nephropathy has become the number-one cause of end-stage renal disease in the United States, accounting for 40% of all new cases, he said.

The earliest clinical evidence of nephropathy is persistent microalbuminuria. Among 3,259 participants in the SEARCH for Diabetes in Youth study, Dr. Maahs and coworkers found that the prevalence of an elevated albumin-to-creatinine ratio indicative of microalbuminuria was 9.2% among type 1 and 22.2% in type 2 diabetic individuals under age 20 (Diabetes Care 2007;30:2593-8).

Because persistent microalbuminuria is the reversible stage of diabetic nephropathy if treated with an ACE inhibitor or angiotensin receptor blocker along with intensified glycemic control, smoking cessation, and treatment of hypertension if present, the American Diabetes Association recommends performing an annual test to assess urine albumin excretion in all patients who've had type 1 diabetes for at least 5 years and in all type 2 diabetes patients starting at the time of diagnosis.

The screening for microalbuminuria can be performed by one of three methods: measurement of the albumin to creatinine ratio in a random spot urine; a 24-hour urine collection; or a timed urine collection, often done overnight. A diagnosis of persistent microalbuminuria requires a positive result on two of three tests conducted within a 3-6 month period.

The American Diabetes Association guidelines also call for measurement of serum creatinine at least annually in all adults with diabetes regardless of their degree of urine albumin excretion. The serum creatinine is to be used to estimate GFR.

Because it's important to identify progression to microalbuminuria in a timely way in patients with type 1 diabetes, Dr. Maahs and his coworkers have developed and validated a prediction rule that identifies a subset of patients at high risk. The idea is that a few relatively easily obtainable patient characteristics can be used to help physicians identify a patient subgroup likely to benefit from screening for microalbuminuria more frequently than once yearly.

The prediction rule was developed using data from 1,115 patients in the European Diabetes Prospective Complications Study, then validated in the Finnish Diabetic Nephropathy Study, the Coronary Artery Calcification in Type 1 Diabetes Study, and the Pittsburgh Epidemiology of Diabetes Complication Study. The key variables used in the prediction rule are the albumin excretion rate, body mass index, waist:hip ratio, and a history of ever having smoked.

Thirteen percent of patients progressed to microalbuminuria during 7 years of follow-up. A high-risk subgroup consisting of 8% of the patient population was identified as having a risk of progression of 32% (Diabetologia 2010;53:254-62).

Dr. Maahs disclosed receiving research support from Merck and Eli Lilly.

KEYSTONE, COLO. – Serum cystatin C isn't ready for prime-time use in clinical practice as an alternative to urinary albumin excretion and serum creatinine in screening for diabetic nephropathy, but the unfolding research on this novel biomarker is definitely worth keeping an eye on.

“From a pediatric diabetes perspective, were we to have more data on cystatin C, it would sure be appealing to be able to collect it from a blood sample and not have to try to get overnight urines or even spot urines. This is a biomarker that may pan out as something useful in the future,” Dr. David M. Maahs said at the conference, sponsored by the Children's Diabetes Foundation at Denver.

Growing evidence suggests serum cystatin C provides a more accurate estimate of glomerular filtration rate (GFR) than do predictive equations based upon serum creatinine, such as the widely used Cockroft-Gault or Modification of Diet in Renal Disease equations.

“Cystatin C has been described as like an HbA_1c for renal function,” observed Dr. Maahs of the Barbara Davis Center for Childhood Diabetes and the University of Colorado, Denver.

Cystatin C also appears to be superior to serum creatinine as a predictor of the risk of death and cardiovascular events in the elderly in general (N. Engl. J. Med. 2005;352:2049-60). Furthermore, in an analysis restricted to 691 elderly diabetics in the Cardiovascular Health Study, cystatin C–based estimated GFR predicted mortality more strongly than did serum creatinine–based estimated GFR (Diabetes Care 2009;32:1833-8).

Moreover, in a study of 509 adults with type 1 diabetes followed for 2.5 years, Dr. Maahs and coworkers showed that serum cystatin C predicted progression of subclinical coronary atherosclerosis as reflected by coronary artery calcification better than serum creatinine, estimated glomerular filtration rate, or albumin excretion rate (Diabetes 2007;56:2774-9).

That being said, data on cystatin C's performance in pediatric populations with diabetes remain lacking, he noted.

Serum cystatin C goes up as the GFR goes down. Cystatin C is thought to better reflect GFR than does serum creatinine because it is independent of age, sex, and muscle mass. Cystatin C is a stable protein produced by nucleated cells at a constant rate. It is freely filtered at the glomerulus because of its small molecular mass, it is not reabsorbed, and it is eliminated by the kidneys.

Putting aside for the future the question of cystatin C as a potential tool for following GFR in diabetic patients, Dr. Maahs stressed the importance of following guidelines for screening for diabetic nephropathy in young patients. About 20%-40% of patients with diabetes develop nephropathy. Indeed, diabetic nephropathy has become the number-one cause of end-stage renal disease in the United States, accounting for 40% of all new cases, he said.

The earliest clinical evidence of nephropathy is persistent microalbuminuria. Among 3,259 participants in the SEARCH for Diabetes in Youth study, Dr. Maahs and coworkers found that the prevalence of an elevated albumin-to-creatinine ratio indicative of microalbuminuria was 9.2% among type 1 and 22.2% in type 2 diabetic individuals under age 20 (Diabetes Care 2007;30:2593-8).

Because persistent microalbuminuria is the reversible stage of diabetic nephropathy if treated with an ACE inhibitor or angiotensin receptor blocker along with intensified glycemic control, smoking cessation, and treatment of hypertension if present, the American Diabetes Association recommends performing an annual test to assess urine albumin excretion in all patients who've had type 1 diabetes for at least 5 years and in all type 2 diabetes patients starting at the time of diagnosis.

The screening for microalbuminuria can be performed by one of three methods: measurement of the albumin to creatinine ratio in a random spot urine; a 24-hour urine collection; or a timed urine collection, often done overnight. A diagnosis of persistent microalbuminuria requires a positive result on two of three tests conducted within a 3-6 month period.

The American Diabetes Association guidelines also call for measurement of serum creatinine at least annually in all adults with diabetes regardless of their degree of urine albumin excretion. The serum creatinine is to be used to estimate GFR.

Because it's important to identify progression to microalbuminuria in a timely way in patients with type 1 diabetes, Dr. Maahs and his coworkers have developed and validated a prediction rule that identifies a subset of patients at high risk. The idea is that a few relatively easily obtainable patient characteristics can be used to help physicians identify a patient subgroup likely to benefit from screening for microalbuminuria more frequently than once yearly.

The prediction rule was developed using data from 1,115 patients in the European Diabetes Prospective Complications Study, then validated in the Finnish Diabetic Nephropathy Study, the Coronary Artery Calcification in Type 1 Diabetes Study, and the Pittsburgh Epidemiology of Diabetes Complication Study. The key variables used in the prediction rule are the albumin excretion rate, body mass index, waist:hip ratio, and a history of ever having smoked.

Thirteen percent of patients progressed to microalbuminuria during 7 years of follow-up. A high-risk subgroup consisting of 8% of the patient population was identified as having a risk of progression of 32% (Diabetologia 2010;53:254-62).

Dr. Maahs disclosed receiving research support from Merck and Eli Lilly.

KEYSTONE, COLO. – Serum cystatin C isn't ready for prime-time use in clinical practice as an alternative to urinary albumin excretion and serum creatinine in screening for diabetic nephropathy, but the unfolding research on this novel biomarker is definitely worth keeping an eye on.

“From a pediatric diabetes perspective, were we to have more data on cystatin C, it would sure be appealing to be able to collect it from a blood sample and not have to try to get overnight urines or even spot urines. This is a biomarker that may pan out as something useful in the future,” Dr. David M. Maahs said at the conference, sponsored by the Children's Diabetes Foundation at Denver.

Growing evidence suggests serum cystatin C provides a more accurate estimate of glomerular filtration rate (GFR) than do predictive equations based upon serum creatinine, such as the widely used Cockroft-Gault or Modification of Diet in Renal Disease equations.

“Cystatin C has been described as like an HbA_1c for renal function,” observed Dr. Maahs of the Barbara Davis Center for Childhood Diabetes and the University of Colorado, Denver.

Cystatin C also appears to be superior to serum creatinine as a predictor of the risk of death and cardiovascular events in the elderly in general (N. Engl. J. Med. 2005;352:2049-60). Furthermore, in an analysis restricted to 691 elderly diabetics in the Cardiovascular Health Study, cystatin C–based estimated GFR predicted mortality more strongly than did serum creatinine–based estimated GFR (Diabetes Care 2009;32:1833-8).

Moreover, in a study of 509 adults with type 1 diabetes followed for 2.5 years, Dr. Maahs and coworkers showed that serum cystatin C predicted progression of subclinical coronary atherosclerosis as reflected by coronary artery calcification better than serum creatinine, estimated glomerular filtration rate, or albumin excretion rate (Diabetes 2007;56:2774-9).

That being said, data on cystatin C's performance in pediatric populations with diabetes remain lacking, he noted.

Serum cystatin C goes up as the GFR goes down. Cystatin C is thought to better reflect GFR than does serum creatinine because it is independent of age, sex, and muscle mass. Cystatin C is a stable protein produced by nucleated cells at a constant rate. It is freely filtered at the glomerulus because of its small molecular mass, it is not reabsorbed, and it is eliminated by the kidneys.

Putting aside for the future the question of cystatin C as a potential tool for following GFR in diabetic patients, Dr. Maahs stressed the importance of following guidelines for screening for diabetic nephropathy in young patients. About 20%-40% of patients with diabetes develop nephropathy. Indeed, diabetic nephropathy has become the number-one cause of end-stage renal disease in the United States, accounting for 40% of all new cases, he said.

The earliest clinical evidence of nephropathy is persistent microalbuminuria. Among 3,259 participants in the SEARCH for Diabetes in Youth study, Dr. Maahs and coworkers found that the prevalence of an elevated albumin-to-creatinine ratio indicative of microalbuminuria was 9.2% among type 1 and 22.2% in type 2 diabetic individuals under age 20 (Diabetes Care 2007;30:2593-8).

Because persistent microalbuminuria is the reversible stage of diabetic nephropathy if treated with an ACE inhibitor or angiotensin receptor blocker along with intensified glycemic control, smoking cessation, and treatment of hypertension if present, the American Diabetes Association recommends performing an annual test to assess urine albumin excretion in all patients who've had type 1 diabetes for at least 5 years and in all type 2 diabetes patients starting at the time of diagnosis.

The screening for microalbuminuria can be performed by one of three methods: measurement of the albumin to creatinine ratio in a random spot urine; a 24-hour urine collection; or a timed urine collection, often done overnight. A diagnosis of persistent microalbuminuria requires a positive result on two of three tests conducted within a 3-6 month period.

The American Diabetes Association guidelines also call for measurement of serum creatinine at least annually in all adults with diabetes regardless of their degree of urine albumin excretion. The serum creatinine is to be used to estimate GFR.

Because it's important to identify progression to microalbuminuria in a timely way in patients with type 1 diabetes, Dr. Maahs and his coworkers have developed and validated a prediction rule that identifies a subset of patients at high risk. The idea is that a few relatively easily obtainable patient characteristics can be used to help physicians identify a patient subgroup likely to benefit from screening for microalbuminuria more frequently than once yearly.

The prediction rule was developed using data from 1,115 patients in the European Diabetes Prospective Complications Study, then validated in the Finnish Diabetic Nephropathy Study, the Coronary Artery Calcification in Type 1 Diabetes Study, and the Pittsburgh Epidemiology of Diabetes Complication Study. The key variables used in the prediction rule are the albumin excretion rate, body mass index, waist:hip ratio, and a history of ever having smoked.

Thirteen percent of patients progressed to microalbuminuria during 7 years of follow-up. A high-risk subgroup consisting of 8% of the patient population was identified as having a risk of progression of 32% (Diabetologia 2010;53:254-62).

Dr. Maahs disclosed receiving research support from Merck and Eli Lilly.

KEYSTONE, COLO. – Most pediatric endocrinologists rely on metformin as the linchpin in treating new-onset type 2 diabetes in adolescents, adding insulin in those who are in poor glycemic control.

“This isn't an evidence-based treatment algorithm. There aren't any studies in kids to guide us. But this is the current practice among most pediatric endocrinologists who treat a lot of youths with type 2 diabetes,” Dr. Phil Zeitler said at the meeting, sponsored by the Children's Diabetes Foundation at Denver.

Dr. Zeitler is study chair for the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY), a large, ongoing, multicenter, NIH-sponsored study.

For the new-onset type 2 diabetic teen who is nonketotic and in “reasonable” glycemic control, current practice among most specialists is to start metformin at 500 mg/day, along with initiating standard diabetes education with an added focus on the basics of lifestyle change and weight loss. The daily dose of metformin should be increased by no more than 500 mg a week to a target of 2,000 mg/day. It is crucial to titrate the drug slowly to minimize GI side effects.

“I tell my patients that I want them on 2,000 mg/day and I really don't care how long it takes to get there. If they're not feeling well after a week, they stay at that dose for the next week,” said Dr. Zeitler, professor of pediatrics and clinical science at the University of Colorado, Denver, and medical director of the Children's Hospital Clinical Translational Research Center.

He stressed that what constitutes “reasonable” glycemic control in a new-onset patient is an individual physician decision because there is no evidence to provide guidance. He often uses an HbA_1c of about 9% as a cutoff. Other pediatric endocrinologists use 10%, and still others use an HbA_1c closer to 8% as their threshold for turning to insulin, he noted.

Insulin isn't generally considered first-line therapy for type 2 diabetes in adults. However, teens have far fewer approved treatment options. Insulin is effective, it acts synergistically with oral metformin to reduce glucose toxicity, and it sends the adolescent a message that this is a disease to be taken seriously.

For these reasons, Dr. Zeitler recommended the following strategy for a new-onset type 2 diabetic adolescent in poor glycemic control who has no acidosis: Start metformin and diabetes education as previously described, along with 15-30 U of basal insulin given at night or whenever family supervision is most likely in order to ensure adherence. “These kids will not take that insulin on their own,” he continued.

Once glucose control is attained – as signified by an HbA_1c below 6.5% – wean the patient off insulin.

“There is no evidence that weaning slowly is any more effective than weaning quickly in these patients. You might as well find out if the patient is going to be on metformin alone,” said Dr. Zeitler.

In a new-onset patient with acidosis and in poor glycemic control, start the patient on metformin and use insulin as in a type 1 patient until the acidosis resolves, then wean the patient off insulin.

For patients who can't maintain an HbA_1c below 6.5% on full-dose metformin alone, he recommended adding once-daily insulin detemir or glargine, starting at 10-20 U/day. If the patient can't maintain the target HbA_1c despite long-acting insulin at a dose of 1 U/kg of body weight and there is evidence of postprandial hyperglycemia, consider adding short-acting insulin. But, there's a caveat.

“Keep in mind that this is going to substantially increase the burden on these children and therefore you may, in fact, not get any benefit because they won't do it. You need to have a good conversation with the family and figure out what's going to work,” Dr. Zeitler said.

Metformin is the sole oral agent approved for use in pediatric type 2 diabetes. It is well studied in adults, safe, and now costs no more than generic oral sulfonylureas. Among its desirable qualities are that it induces weight loss, there is mild improvement in lipids, it improves hirsutism and menstrual irregularities, and it may improve hepatic steatosis. Lactic acidosis, once thought to be a serious problem with metformin, was absolved in a meta-analysis of 40,000 patients. Nonetheless, the drug shouldn't be used in adolescents who have substantial renal disease, are dehydrated, or are having a radiologic procedure.

Sulfonylureas are rarely used in kids because they cause weight gain, and hypoglycemia is a much bigger problem than in adults.

“It may be [that] the balance of insulin resistance and beta-cell function is different in kids and adults. Kids actually have relatively well-maintained beta-cell function, so when you give them a secretagogue, they're able to produce large amounts of insulin, leading to substantial hypoglycemia. I have not been able to effectively use a sulfonylurea in a kid without substantial hypoglycemia,” the physician continued.

The thiazolidinediones are well studied in adults, where they reduce HbA_1c by about 1% and might prolong beta-cell function, a highly desirable attribute in a teenager who may live with type 2 diabetes for another 50 years. But there are no published studies on thiazolidinediones for treatment of type 2 diabetes in youth, and the drugs have substantial side effects, especially weight gain.

The glucagon-like peptide-1 analogue exenatide (Byetta) is the subject of an ongoing clinical trial in pediatric type 2 diabetes. Exenatide slows gastric emptying, increases insulin secretion, and causes weight loss, but must be administered by twice-daily injections before meals.

The dipeptidylpeptidase-4 inhibitors sitagliptin (Januvia) and saxagliptin (Onglyza) have actions similar to exenatide, but without the weight-loss feature. However, they can be taken orally. Pediatric trials are in the design phase.

Dr. Zeitler serves as an advisor to numerous pharmaceutical companies.

'I have not been able to effectively use a sulfonylurea in a kid without substantial hypoglycemia.'

Source DR. ZEITLER

KEYSTONE, COLO. – Most pediatric endocrinologists rely on metformin as the linchpin in treating new-onset type 2 diabetes in adolescents, adding insulin in those who are in poor glycemic control.

“This isn't an evidence-based treatment algorithm. There aren't any studies in kids to guide us. But this is the current practice among most pediatric endocrinologists who treat a lot of youths with type 2 diabetes,” Dr. Phil Zeitler said at the meeting, sponsored by the Children's Diabetes Foundation at Denver.

Dr. Zeitler is study chair for the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY), a large, ongoing, multicenter, NIH-sponsored study.

For the new-onset type 2 diabetic teen who is nonketotic and in “reasonable” glycemic control, current practice among most specialists is to start metformin at 500 mg/day, along with initiating standard diabetes education with an added focus on the basics of lifestyle change and weight loss. The daily dose of metformin should be increased by no more than 500 mg a week to a target of 2,000 mg/day. It is crucial to titrate the drug slowly to minimize GI side effects.

“I tell my patients that I want them on 2,000 mg/day and I really don't care how long it takes to get there. If they're not feeling well after a week, they stay at that dose for the next week,” said Dr. Zeitler, professor of pediatrics and clinical science at the University of Colorado, Denver, and medical director of the Children's Hospital Clinical Translational Research Center.

He stressed that what constitutes “reasonable” glycemic control in a new-onset patient is an individual physician decision because there is no evidence to provide guidance. He often uses an HbA_1c of about 9% as a cutoff. Other pediatric endocrinologists use 10%, and still others use an HbA_1c closer to 8% as their threshold for turning to insulin, he noted.

Insulin isn't generally considered first-line therapy for type 2 diabetes in adults. However, teens have far fewer approved treatment options. Insulin is effective, it acts synergistically with oral metformin to reduce glucose toxicity, and it sends the adolescent a message that this is a disease to be taken seriously.

For these reasons, Dr. Zeitler recommended the following strategy for a new-onset type 2 diabetic adolescent in poor glycemic control who has no acidosis: Start metformin and diabetes education as previously described, along with 15-30 U of basal insulin given at night or whenever family supervision is most likely in order to ensure adherence. “These kids will not take that insulin on their own,” he continued.

Once glucose control is attained – as signified by an HbA_1c below 6.5% – wean the patient off insulin.

“There is no evidence that weaning slowly is any more effective than weaning quickly in these patients. You might as well find out if the patient is going to be on metformin alone,” said Dr. Zeitler.

In a new-onset patient with acidosis and in poor glycemic control, start the patient on metformin and use insulin as in a type 1 patient until the acidosis resolves, then wean the patient off insulin.

For patients who can't maintain an HbA_1c below 6.5% on full-dose metformin alone, he recommended adding once-daily insulin detemir or glargine, starting at 10-20 U/day. If the patient can't maintain the target HbA_1c despite long-acting insulin at a dose of 1 U/kg of body weight and there is evidence of postprandial hyperglycemia, consider adding short-acting insulin. But, there's a caveat.

“Keep in mind that this is going to substantially increase the burden on these children and therefore you may, in fact, not get any benefit because they won't do it. You need to have a good conversation with the family and figure out what's going to work,” Dr. Zeitler said.

Metformin is the sole oral agent approved for use in pediatric type 2 diabetes. It is well studied in adults, safe, and now costs no more than generic oral sulfonylureas. Among its desirable qualities are that it induces weight loss, there is mild improvement in lipids, it improves hirsutism and menstrual irregularities, and it may improve hepatic steatosis. Lactic acidosis, once thought to be a serious problem with metformin, was absolved in a meta-analysis of 40,000 patients. Nonetheless, the drug shouldn't be used in adolescents who have substantial renal disease, are dehydrated, or are having a radiologic procedure.

Sulfonylureas are rarely used in kids because they cause weight gain, and hypoglycemia is a much bigger problem than in adults.

“It may be [that] the balance of insulin resistance and beta-cell function is different in kids and adults. Kids actually have relatively well-maintained beta-cell function, so when you give them a secretagogue, they're able to produce large amounts of insulin, leading to substantial hypoglycemia. I have not been able to effectively use a sulfonylurea in a kid without substantial hypoglycemia,” the physician continued.

The thiazolidinediones are well studied in adults, where they reduce HbA_1c by about 1% and might prolong beta-cell function, a highly desirable attribute in a teenager who may live with type 2 diabetes for another 50 years. But there are no published studies on thiazolidinediones for treatment of type 2 diabetes in youth, and the drugs have substantial side effects, especially weight gain.

The glucagon-like peptide-1 analogue exenatide (Byetta) is the subject of an ongoing clinical trial in pediatric type 2 diabetes. Exenatide slows gastric emptying, increases insulin secretion, and causes weight loss, but must be administered by twice-daily injections before meals.

The dipeptidylpeptidase-4 inhibitors sitagliptin (Januvia) and saxagliptin (Onglyza) have actions similar to exenatide, but without the weight-loss feature. However, they can be taken orally. Pediatric trials are in the design phase.

Dr. Zeitler serves as an advisor to numerous pharmaceutical companies.

'I have not been able to effectively use a sulfonylurea in a kid without substantial hypoglycemia.'

Source DR. ZEITLER

KEYSTONE, COLO. – Most pediatric endocrinologists rely on metformin as the linchpin in treating new-onset type 2 diabetes in adolescents, adding insulin in those who are in poor glycemic control.

“This isn't an evidence-based treatment algorithm. There aren't any studies in kids to guide us. But this is the current practice among most pediatric endocrinologists who treat a lot of youths with type 2 diabetes,” Dr. Phil Zeitler said at the meeting, sponsored by the Children's Diabetes Foundation at Denver.

Dr. Zeitler is study chair for the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY), a large, ongoing, multicenter, NIH-sponsored study.

For the new-onset type 2 diabetic teen who is nonketotic and in “reasonable” glycemic control, current practice among most specialists is to start metformin at 500 mg/day, along with initiating standard diabetes education with an added focus on the basics of lifestyle change and weight loss. The daily dose of metformin should be increased by no more than 500 mg a week to a target of 2,000 mg/day. It is crucial to titrate the drug slowly to minimize GI side effects.

“I tell my patients that I want them on 2,000 mg/day and I really don't care how long it takes to get there. If they're not feeling well after a week, they stay at that dose for the next week,” said Dr. Zeitler, professor of pediatrics and clinical science at the University of Colorado, Denver, and medical director of the Children's Hospital Clinical Translational Research Center.

He stressed that what constitutes “reasonable” glycemic control in a new-onset patient is an individual physician decision because there is no evidence to provide guidance. He often uses an HbA_1c of about 9% as a cutoff. Other pediatric endocrinologists use 10%, and still others use an HbA_1c closer to 8% as their threshold for turning to insulin, he noted.

Insulin isn't generally considered first-line therapy for type 2 diabetes in adults. However, teens have far fewer approved treatment options. Insulin is effective, it acts synergistically with oral metformin to reduce glucose toxicity, and it sends the adolescent a message that this is a disease to be taken seriously.

For these reasons, Dr. Zeitler recommended the following strategy for a new-onset type 2 diabetic adolescent in poor glycemic control who has no acidosis: Start metformin and diabetes education as previously described, along with 15-30 U of basal insulin given at night or whenever family supervision is most likely in order to ensure adherence. “These kids will not take that insulin on their own,” he continued.

Once glucose control is attained – as signified by an HbA_1c below 6.5% – wean the patient off insulin.

“There is no evidence that weaning slowly is any more effective than weaning quickly in these patients. You might as well find out if the patient is going to be on metformin alone,” said Dr. Zeitler.

In a new-onset patient with acidosis and in poor glycemic control, start the patient on metformin and use insulin as in a type 1 patient until the acidosis resolves, then wean the patient off insulin.

For patients who can't maintain an HbA_1c below 6.5% on full-dose metformin alone, he recommended adding once-daily insulin detemir or glargine, starting at 10-20 U/day. If the patient can't maintain the target HbA_1c despite long-acting insulin at a dose of 1 U/kg of body weight and there is evidence of postprandial hyperglycemia, consider adding short-acting insulin. But, there's a caveat.

“Keep in mind that this is going to substantially increase the burden on these children and therefore you may, in fact, not get any benefit because they won't do it. You need to have a good conversation with the family and figure out what's going to work,” Dr. Zeitler said.

Metformin is the sole oral agent approved for use in pediatric type 2 diabetes. It is well studied in adults, safe, and now costs no more than generic oral sulfonylureas. Among its desirable qualities are that it induces weight loss, there is mild improvement in lipids, it improves hirsutism and menstrual irregularities, and it may improve hepatic steatosis. Lactic acidosis, once thought to be a serious problem with metformin, was absolved in a meta-analysis of 40,000 patients. Nonetheless, the drug shouldn't be used in adolescents who have substantial renal disease, are dehydrated, or are having a radiologic procedure.

Sulfonylureas are rarely used in kids because they cause weight gain, and hypoglycemia is a much bigger problem than in adults.

“It may be [that] the balance of insulin resistance and beta-cell function is different in kids and adults. Kids actually have relatively well-maintained beta-cell function, so when you give them a secretagogue, they're able to produce large amounts of insulin, leading to substantial hypoglycemia. I have not been able to effectively use a sulfonylurea in a kid without substantial hypoglycemia,” the physician continued.

The thiazolidinediones are well studied in adults, where they reduce HbA_1c by about 1% and might prolong beta-cell function, a highly desirable attribute in a teenager who may live with type 2 diabetes for another 50 years. But there are no published studies on thiazolidinediones for treatment of type 2 diabetes in youth, and the drugs have substantial side effects, especially weight gain.

The glucagon-like peptide-1 analogue exenatide (Byetta) is the subject of an ongoing clinical trial in pediatric type 2 diabetes. Exenatide slows gastric emptying, increases insulin secretion, and causes weight loss, but must be administered by twice-daily injections before meals.

The dipeptidylpeptidase-4 inhibitors sitagliptin (Januvia) and saxagliptin (Onglyza) have actions similar to exenatide, but without the weight-loss feature. However, they can be taken orally. Pediatric trials are in the design phase.

Dr. Zeitler serves as an advisor to numerous pharmaceutical companies.

'I have not been able to effectively use a sulfonylurea in a kid without substantial hypoglycemia.'

Source DR. ZEITLER

ROME – Cardiovascular risk profiles in osteoarthritis patients are, on average, comparable with those in patients with rheumatoid arthritis, according to a Dutch study.

In recent years, much attention has been focused on the elevated risk of cardiovascular events in patients with rheumatoid arthritis, as a consequence of their increased prevalence of the standard cardiovascular risk factors coupled with a further boost in risk resulting from the chronic systemic inflammatory disease process.

The cardiovascular risk associated with osteoarthritis has received far less attention, Dr. Inger Meek observed.

She determined the cardiovascular risk profiles of 285 consecutive rheumatoid arthritis patients and 112 consecutive osteoarthritis patients using the SCORE (Systematic Coronary Risk Evaluation) system, which is routinely employed in European clinical practice in lieu of the Framingham risk score.

The two populations were similar in terms of mean age and sex. The mean disease duration of the rheumatoid arthritis patients was 6.8 years.

In all, 18% of the osteoarthritis patients in the study had a greater-than-10% estimated 10-year risk of a fatal cardiovascular event by SCORE, as did 15% of rheumatoid arthritis patients, according to Dr. Meek, who is with the University of Twente in Enschede, the Netherlands.

Hypercholesterolemia was significantly more prevalent in the osteoarthritis patients, by a margin of 45%, compared with 29% for the rheumatoid arthritis patients.

The two groups did not differ significantly in terms of the other elements of SCORE (smoking status, systolic blood pressure, age, and sex).

The SCORE system, developed by the European Society of Cardiology, is based upon 3 million person-years of observation, and doesn't factor in body mass index, Dr. Meek noted.

Obesity is a well-established cardiovascular risk factor, and its prevalence is greatly increased in patients with osteoarthritis. Thus, SCORE likely underestimates their true cardiovascular mortality risk.

Recent evidence-based recommendations by the European League Against Rheumatism advise physicians to apply a 1.5 multiplication factor to the conventional cardiovascular mortality risk SCORE in rheumatoid arthritis patients who meet two of three criteria: disease duration greater than 10 years, rheumatoid factor or anti–cyclic citrullinated peptide positivity, or extra-articular disease manifestations (Ann. Rheum. Dis. 2010;69:325-31).

This is designed to account for the heightened cardiovascular risk imposed by a high degree of systemic inflammation.

The substantial percentage of osteoarthritis patients in this study who had a greater-than-10% estimated likelihood of cardiovascular death within 10 years is of particular concern, Dr. Meek stressed, because the prevalence of osteoarthritis is expected to mushroom in the near future as a result of the graying of the baby boom generation.

Dr. Johannes W.J. Bijlsma of the University Medical Center Utrecht (the Netherlands) commented that the take-home message of Dr. Meek's study is that physicians need to be aware that it's not only their rheumatoid arthritis patients but also their osteoarthritis patients who are at increased cardiovascular risk.

Dr. Meek declared having no financial conflicts.

ROME – Cardiovascular risk profiles in osteoarthritis patients are, on average, comparable with those in patients with rheumatoid arthritis, according to a Dutch study.

In recent years, much attention has been focused on the elevated risk of cardiovascular events in patients with rheumatoid arthritis, as a consequence of their increased prevalence of the standard cardiovascular risk factors coupled with a further boost in risk resulting from the chronic systemic inflammatory disease process.

The cardiovascular risk associated with osteoarthritis has received far less attention, Dr. Inger Meek observed.

She determined the cardiovascular risk profiles of 285 consecutive rheumatoid arthritis patients and 112 consecutive osteoarthritis patients using the SCORE (Systematic Coronary Risk Evaluation) system, which is routinely employed in European clinical practice in lieu of the Framingham risk score.

The two populations were similar in terms of mean age and sex. The mean disease duration of the rheumatoid arthritis patients was 6.8 years.

In all, 18% of the osteoarthritis patients in the study had a greater-than-10% estimated 10-year risk of a fatal cardiovascular event by SCORE, as did 15% of rheumatoid arthritis patients, according to Dr. Meek, who is with the University of Twente in Enschede, the Netherlands.

Hypercholesterolemia was significantly more prevalent in the osteoarthritis patients, by a margin of 45%, compared with 29% for the rheumatoid arthritis patients.

The two groups did not differ significantly in terms of the other elements of SCORE (smoking status, systolic blood pressure, age, and sex).

The SCORE system, developed by the European Society of Cardiology, is based upon 3 million person-years of observation, and doesn't factor in body mass index, Dr. Meek noted.

Obesity is a well-established cardiovascular risk factor, and its prevalence is greatly increased in patients with osteoarthritis. Thus, SCORE likely underestimates their true cardiovascular mortality risk.

Recent evidence-based recommendations by the European League Against Rheumatism advise physicians to apply a 1.5 multiplication factor to the conventional cardiovascular mortality risk SCORE in rheumatoid arthritis patients who meet two of three criteria: disease duration greater than 10 years, rheumatoid factor or anti–cyclic citrullinated peptide positivity, or extra-articular disease manifestations (Ann. Rheum. Dis. 2010;69:325-31).

This is designed to account for the heightened cardiovascular risk imposed by a high degree of systemic inflammation.

The substantial percentage of osteoarthritis patients in this study who had a greater-than-10% estimated likelihood of cardiovascular death within 10 years is of particular concern, Dr. Meek stressed, because the prevalence of osteoarthritis is expected to mushroom in the near future as a result of the graying of the baby boom generation.

Dr. Johannes W.J. Bijlsma of the University Medical Center Utrecht (the Netherlands) commented that the take-home message of Dr. Meek's study is that physicians need to be aware that it's not only their rheumatoid arthritis patients but also their osteoarthritis patients who are at increased cardiovascular risk.

Dr. Meek declared having no financial conflicts.

ROME – Cardiovascular risk profiles in osteoarthritis patients are, on average, comparable with those in patients with rheumatoid arthritis, according to a Dutch study.

In recent years, much attention has been focused on the elevated risk of cardiovascular events in patients with rheumatoid arthritis, as a consequence of their increased prevalence of the standard cardiovascular risk factors coupled with a further boost in risk resulting from the chronic systemic inflammatory disease process.

The cardiovascular risk associated with osteoarthritis has received far less attention, Dr. Inger Meek observed.

She determined the cardiovascular risk profiles of 285 consecutive rheumatoid arthritis patients and 112 consecutive osteoarthritis patients using the SCORE (Systematic Coronary Risk Evaluation) system, which is routinely employed in European clinical practice in lieu of the Framingham risk score.

The two populations were similar in terms of mean age and sex. The mean disease duration of the rheumatoid arthritis patients was 6.8 years.

In all, 18% of the osteoarthritis patients in the study had a greater-than-10% estimated 10-year risk of a fatal cardiovascular event by SCORE, as did 15% of rheumatoid arthritis patients, according to Dr. Meek, who is with the University of Twente in Enschede, the Netherlands.

Hypercholesterolemia was significantly more prevalent in the osteoarthritis patients, by a margin of 45%, compared with 29% for the rheumatoid arthritis patients.

The two groups did not differ significantly in terms of the other elements of SCORE (smoking status, systolic blood pressure, age, and sex).

The SCORE system, developed by the European Society of Cardiology, is based upon 3 million person-years of observation, and doesn't factor in body mass index, Dr. Meek noted.

Obesity is a well-established cardiovascular risk factor, and its prevalence is greatly increased in patients with osteoarthritis. Thus, SCORE likely underestimates their true cardiovascular mortality risk.

Recent evidence-based recommendations by the European League Against Rheumatism advise physicians to apply a 1.5 multiplication factor to the conventional cardiovascular mortality risk SCORE in rheumatoid arthritis patients who meet two of three criteria: disease duration greater than 10 years, rheumatoid factor or anti–cyclic citrullinated peptide positivity, or extra-articular disease manifestations (Ann. Rheum. Dis. 2010;69:325-31).

This is designed to account for the heightened cardiovascular risk imposed by a high degree of systemic inflammation.

The substantial percentage of osteoarthritis patients in this study who had a greater-than-10% estimated likelihood of cardiovascular death within 10 years is of particular concern, Dr. Meek stressed, because the prevalence of osteoarthritis is expected to mushroom in the near future as a result of the graying of the baby boom generation.

Dr. Johannes W.J. Bijlsma of the University Medical Center Utrecht (the Netherlands) commented that the take-home message of Dr. Meek's study is that physicians need to be aware that it's not only their rheumatoid arthritis patients but also their osteoarthritis patients who are at increased cardiovascular risk.

Dr. Meek declared having no financial conflicts.

ROME – N-terminal prohormone brain natriuretic peptide level provides a simple, previously untapped, and powerful predictor of cardiovascular risk in arthritis patients on long-term NSAID therapy, according to a large prospective study.

“Risk stratification based on NT-proBNP may offer a handle to cope with the risk of cardiovascular side effects of nonsteroidal anti-inflammatory drugs in our aging population,” Dr. Kay Brune said while presenting the cardiac biomarker analysis from the Multinational Etoricoxib and Diclofenac Long-term (MEDAL) study at the meeting.

MEDAL involved more than 34,000 patients with rheumatoid arthritis or osteoarthritis who were randomized to receive treatment with either the cyclooxygenase-2 (COX-2) selective inhibitor etoricoxib or diclofenac. The primary outcomes have previously been reported (Lancet 2006;368:1771-81).

Dr. Brune presented a secondary cardiac biomarker analysis involving the 6,273 MEDAL participants for whom baseline plasma NT-proBNP and high-sensitivity C-reactive protein measurements were available.

The two treatment arms were combined for this analysis because the 2-year thrombotic cardiovascular event rates were virtually identical in the etoricoxib- and diclofenac-treated subjects, she explained.

The key new finding was that baseline NT-proBNP showed a strong, graded relationship with 2-year rates of myocardial infarction, stroke, heart failure, and cardiovascular death, said Dr. Brune, professor of clinical pharmacology at the University of Erlangen (Germany).

Patients with a baseline NT-proBNP level below the median of 78 pg/mL had zero incidence of heart failure at 2 years of follow-up.

Their combined thrombotic cardiovascular event rate – consisting of myocardial infarction, stroke, and cardiovascular death – was less than 1% after 2 years of NSAID therapy.

In contrast, the patients who were in the third quartile for NT-proBNP, with a value of 78-148 pg/mL, had a 2.3% incidence of the combined end point of myocardial infarction, stroke, cardiovascular death, and heart failure, while those in the top quartile had an incidence of 4.4%.

After adjustment for patient demographics, type of arthritis, and standard cardiovascular risk factors including hypertension, NT-proBNP remained strongly predictive of cardiovascular outcomes, Dr. Brune said.

The implication of these results is that if an arthritis patient has an NT-proBNP value above the median, NSAID therapy may not be a good option from the standpoint of cardiovascular risk, which is already increased in rheumatoid arthritis patients above what would be predicted by the standard cardiovascular risk factors.

And when an arthritis patient who is already on long-term NSAID therapy develops a high NT-proBNP, it is time to consider alternative strategies for pain management, the physician said at the meeting.

NT-proBNP is a marker of cardiac function widely used in clinical practice for screening, diagnosing, and monitoring patients with heart failure.

Baseline C-reactive protein level was not associated with cardiovascular event rates in the MEDAL analysis.

Dr. Brune disclosed having received research grant support from Merck & Co. and Roche Diagnostics, which funded the study. MEDAL was funded by Merck.

ROME – N-terminal prohormone brain natriuretic peptide level provides a simple, previously untapped, and powerful predictor of cardiovascular risk in arthritis patients on long-term NSAID therapy, according to a large prospective study.

“Risk stratification based on NT-proBNP may offer a handle to cope with the risk of cardiovascular side effects of nonsteroidal anti-inflammatory drugs in our aging population,” Dr. Kay Brune said while presenting the cardiac biomarker analysis from the Multinational Etoricoxib and Diclofenac Long-term (MEDAL) study at the meeting.

MEDAL involved more than 34,000 patients with rheumatoid arthritis or osteoarthritis who were randomized to receive treatment with either the cyclooxygenase-2 (COX-2) selective inhibitor etoricoxib or diclofenac. The primary outcomes have previously been reported (Lancet 2006;368:1771-81).

Dr. Brune presented a secondary cardiac biomarker analysis involving the 6,273 MEDAL participants for whom baseline plasma NT-proBNP and high-sensitivity C-reactive protein measurements were available.

The two treatment arms were combined for this analysis because the 2-year thrombotic cardiovascular event rates were virtually identical in the etoricoxib- and diclofenac-treated subjects, she explained.

The key new finding was that baseline NT-proBNP showed a strong, graded relationship with 2-year rates of myocardial infarction, stroke, heart failure, and cardiovascular death, said Dr. Brune, professor of clinical pharmacology at the University of Erlangen (Germany).

Patients with a baseline NT-proBNP level below the median of 78 pg/mL had zero incidence of heart failure at 2 years of follow-up.

Their combined thrombotic cardiovascular event rate – consisting of myocardial infarction, stroke, and cardiovascular death – was less than 1% after 2 years of NSAID therapy.

In contrast, the patients who were in the third quartile for NT-proBNP, with a value of 78-148 pg/mL, had a 2.3% incidence of the combined end point of myocardial infarction, stroke, cardiovascular death, and heart failure, while those in the top quartile had an incidence of 4.4%.

After adjustment for patient demographics, type of arthritis, and standard cardiovascular risk factors including hypertension, NT-proBNP remained strongly predictive of cardiovascular outcomes, Dr. Brune said.

The implication of these results is that if an arthritis patient has an NT-proBNP value above the median, NSAID therapy may not be a good option from the standpoint of cardiovascular risk, which is already increased in rheumatoid arthritis patients above what would be predicted by the standard cardiovascular risk factors.

And when an arthritis patient who is already on long-term NSAID therapy develops a high NT-proBNP, it is time to consider alternative strategies for pain management, the physician said at the meeting.

NT-proBNP is a marker of cardiac function widely used in clinical practice for screening, diagnosing, and monitoring patients with heart failure.

Baseline C-reactive protein level was not associated with cardiovascular event rates in the MEDAL analysis.

Dr. Brune disclosed having received research grant support from Merck & Co. and Roche Diagnostics, which funded the study. MEDAL was funded by Merck.

ROME – N-terminal prohormone brain natriuretic peptide level provides a simple, previously untapped, and powerful predictor of cardiovascular risk in arthritis patients on long-term NSAID therapy, according to a large prospective study.

“Risk stratification based on NT-proBNP may offer a handle to cope with the risk of cardiovascular side effects of nonsteroidal anti-inflammatory drugs in our aging population,” Dr. Kay Brune said while presenting the cardiac biomarker analysis from the Multinational Etoricoxib and Diclofenac Long-term (MEDAL) study at the meeting.

MEDAL involved more than 34,000 patients with rheumatoid arthritis or osteoarthritis who were randomized to receive treatment with either the cyclooxygenase-2 (COX-2) selective inhibitor etoricoxib or diclofenac. The primary outcomes have previously been reported (Lancet 2006;368:1771-81).

Dr. Brune presented a secondary cardiac biomarker analysis involving the 6,273 MEDAL participants for whom baseline plasma NT-proBNP and high-sensitivity C-reactive protein measurements were available.

The two treatment arms were combined for this analysis because the 2-year thrombotic cardiovascular event rates were virtually identical in the etoricoxib- and diclofenac-treated subjects, she explained.

The key new finding was that baseline NT-proBNP showed a strong, graded relationship with 2-year rates of myocardial infarction, stroke, heart failure, and cardiovascular death, said Dr. Brune, professor of clinical pharmacology at the University of Erlangen (Germany).

Patients with a baseline NT-proBNP level below the median of 78 pg/mL had zero incidence of heart failure at 2 years of follow-up.

Their combined thrombotic cardiovascular event rate – consisting of myocardial infarction, stroke, and cardiovascular death – was less than 1% after 2 years of NSAID therapy.

In contrast, the patients who were in the third quartile for NT-proBNP, with a value of 78-148 pg/mL, had a 2.3% incidence of the combined end point of myocardial infarction, stroke, cardiovascular death, and heart failure, while those in the top quartile had an incidence of 4.4%.

After adjustment for patient demographics, type of arthritis, and standard cardiovascular risk factors including hypertension, NT-proBNP remained strongly predictive of cardiovascular outcomes, Dr. Brune said.

The implication of these results is that if an arthritis patient has an NT-proBNP value above the median, NSAID therapy may not be a good option from the standpoint of cardiovascular risk, which is already increased in rheumatoid arthritis patients above what would be predicted by the standard cardiovascular risk factors.

And when an arthritis patient who is already on long-term NSAID therapy develops a high NT-proBNP, it is time to consider alternative strategies for pain management, the physician said at the meeting.

NT-proBNP is a marker of cardiac function widely used in clinical practice for screening, diagnosing, and monitoring patients with heart failure.

Baseline C-reactive protein level was not associated with cardiovascular event rates in the MEDAL analysis.

Dr. Brune disclosed having received research grant support from Merck & Co. and Roche Diagnostics, which funded the study. MEDAL was funded by Merck.

ATLANTA – St. John's wort appears to convert clopidogrel hyporesponders into robust responders.

This raises the intriguing possibility that the herbal therapy might provide a “twofer”: enhanced platelet inhibition in clopidogrel (Plavix) hyporesponders, plus a well-studied antidepressant effect that could be of particular value in patients with coronary artery disease, Dr. Wei C. Lau said at the annual scientific session of the American College of Cardiology.

“Depression plays a big role in coronary artery disease, and addressing depression is a big part of our cardiac rehab program. The next step in our research is going to be St. John's wort versus placebo to see if we get a double whammy: a treatment that improves platelet inhibition in patients on clopidogrel while also improving the psyche,” added Dr. Lau, director of adult cardiovascular and thoracic anesthesiology at the University of Michigan Cardiovascular Center, Ann Arbor.

It's now well established that about 20% of clopidogrel-treated patients are low responders to the platelet-inhibiting drug, placing them at increased risk of major thrombotic events related to coronary stenting.

The recommended solutions at this point are to double the maintenance dose from 75 to 150 mg/day, switch to an alternative platelet inhibitor, or add another agent such as cilostazol (Pletal). But doubling the clopidogrel dose raises the associated bleeding risk, while cilostazol is a relatively expensive drug with compliance issues related to its twice-daily dosing.

“I think we can do this better with St. John's wort,” according to Dr. Lau. “It's a dollar a pill once daily.”

Clopidogrel is a prodrug activated by the cytochrome P450 isoenzyme. St. John's wort (Hypericum perforatum) is a potent inducer of increased metabolic activity of the CYP 3A4 enzyme, with resultant enhanced platelet-inhibiting effects.

Dr. Lau and his coinvestigators, including Dr. Paul A. Gurbel of Johns Hopkins University, Baltimore, measured platelet function in 62 heart patients on chronic maintenance clopidogrel at the standard 75 mg once daily. They identified 19 patients as clopidogrel hyporesponders with suboptimal platelet inhibition. They randomized these 19 patients in double-blind fashion to St. John's wort at 300 mg once daily or placebo for 14 days while continuing on clopidogrel, then repeated the platelet aggregation studies.

Platelet inhibition improved by 20% in the St. John's wort group while remaining unchanged in controls. In an earlier study involving 10 clopidogrel-hyporesponsive healthy volunteers, 2 weeks of St. John's wort at 300 mg thrice daily boosted platelet inhibition by 36%.

St. John's wort's effects on the cytochrome P450 isoenzyme could in theory affect the metabolism of certain other drugs commonly prescribed in patients with coronary disease. Dr. Lau said that he and his colleagues have demonstrated that, reassuringly, the herbal therapy does not affect LDL levels in patients on statins. However, further prospective randomized studies are clearly needed to firmly establish the safety and efficacy of St. John's wort in converting clopidogrel nonresponders to responders, he added.

In an interview, Dr. Lau said the lack of effective Food and Drug Administration oversight of herbal therapies makes him feel compelled to test every lot of St. John's wort with which he works. He has found, as have others, that concentrations of the active agent often are not as labeled and vary widely from batch to batch with some manufacturers. He has settled on the German Kira brand for its consistency.

Dr. Lau disclosed having no financial interests relevant to this study.

ATLANTA – St. John's wort appears to convert clopidogrel hyporesponders into robust responders.

This raises the intriguing possibility that the herbal therapy might provide a “twofer”: enhanced platelet inhibition in clopidogrel (Plavix) hyporesponders, plus a well-studied antidepressant effect that could be of particular value in patients with coronary artery disease, Dr. Wei C. Lau said at the annual scientific session of the American College of Cardiology.

“Depression plays a big role in coronary artery disease, and addressing depression is a big part of our cardiac rehab program. The next step in our research is going to be St. John's wort versus placebo to see if we get a double whammy: a treatment that improves platelet inhibition in patients on clopidogrel while also improving the psyche,” added Dr. Lau, director of adult cardiovascular and thoracic anesthesiology at the University of Michigan Cardiovascular Center, Ann Arbor.

It's now well established that about 20% of clopidogrel-treated patients are low responders to the platelet-inhibiting drug, placing them at increased risk of major thrombotic events related to coronary stenting.

The recommended solutions at this point are to double the maintenance dose from 75 to 150 mg/day, switch to an alternative platelet inhibitor, or add another agent such as cilostazol (Pletal). But doubling the clopidogrel dose raises the associated bleeding risk, while cilostazol is a relatively expensive drug with compliance issues related to its twice-daily dosing.

“I think we can do this better with St. John's wort,” according to Dr. Lau. “It's a dollar a pill once daily.”

Clopidogrel is a prodrug activated by the cytochrome P450 isoenzyme. St. John's wort (Hypericum perforatum) is a potent inducer of increased metabolic activity of the CYP 3A4 enzyme, with resultant enhanced platelet-inhibiting effects.

Dr. Lau and his coinvestigators, including Dr. Paul A. Gurbel of Johns Hopkins University, Baltimore, measured platelet function in 62 heart patients on chronic maintenance clopidogrel at the standard 75 mg once daily. They identified 19 patients as clopidogrel hyporesponders with suboptimal platelet inhibition. They randomized these 19 patients in double-blind fashion to St. John's wort at 300 mg once daily or placebo for 14 days while continuing on clopidogrel, then repeated the platelet aggregation studies.

Platelet inhibition improved by 20% in the St. John's wort group while remaining unchanged in controls. In an earlier study involving 10 clopidogrel-hyporesponsive healthy volunteers, 2 weeks of St. John's wort at 300 mg thrice daily boosted platelet inhibition by 36%.

St. John's wort's effects on the cytochrome P450 isoenzyme could in theory affect the metabolism of certain other drugs commonly prescribed in patients with coronary disease. Dr. Lau said that he and his colleagues have demonstrated that, reassuringly, the herbal therapy does not affect LDL levels in patients on statins. However, further prospective randomized studies are clearly needed to firmly establish the safety and efficacy of St. John's wort in converting clopidogrel nonresponders to responders, he added.

In an interview, Dr. Lau said the lack of effective Food and Drug Administration oversight of herbal therapies makes him feel compelled to test every lot of St. John's wort with which he works. He has found, as have others, that concentrations of the active agent often are not as labeled and vary widely from batch to batch with some manufacturers. He has settled on the German Kira brand for its consistency.

Dr. Lau disclosed having no financial interests relevant to this study.

ATLANTA – St. John's wort appears to convert clopidogrel hyporesponders into robust responders.

This raises the intriguing possibility that the herbal therapy might provide a “twofer”: enhanced platelet inhibition in clopidogrel (Plavix) hyporesponders, plus a well-studied antidepressant effect that could be of particular value in patients with coronary artery disease, Dr. Wei C. Lau said at the annual scientific session of the American College of Cardiology.

“Depression plays a big role in coronary artery disease, and addressing depression is a big part of our cardiac rehab program. The next step in our research is going to be St. John's wort versus placebo to see if we get a double whammy: a treatment that improves platelet inhibition in patients on clopidogrel while also improving the psyche,” added Dr. Lau, director of adult cardiovascular and thoracic anesthesiology at the University of Michigan Cardiovascular Center, Ann Arbor.

It's now well established that about 20% of clopidogrel-treated patients are low responders to the platelet-inhibiting drug, placing them at increased risk of major thrombotic events related to coronary stenting.

The recommended solutions at this point are to double the maintenance dose from 75 to 150 mg/day, switch to an alternative platelet inhibitor, or add another agent such as cilostazol (Pletal). But doubling the clopidogrel dose raises the associated bleeding risk, while cilostazol is a relatively expensive drug with compliance issues related to its twice-daily dosing.

“I think we can do this better with St. John's wort,” according to Dr. Lau. “It's a dollar a pill once daily.”

Clopidogrel is a prodrug activated by the cytochrome P450 isoenzyme. St. John's wort (Hypericum perforatum) is a potent inducer of increased metabolic activity of the CYP 3A4 enzyme, with resultant enhanced platelet-inhibiting effects.

Dr. Lau and his coinvestigators, including Dr. Paul A. Gurbel of Johns Hopkins University, Baltimore, measured platelet function in 62 heart patients on chronic maintenance clopidogrel at the standard 75 mg once daily. They identified 19 patients as clopidogrel hyporesponders with suboptimal platelet inhibition. They randomized these 19 patients in double-blind fashion to St. John's wort at 300 mg once daily or placebo for 14 days while continuing on clopidogrel, then repeated the platelet aggregation studies.

Platelet inhibition improved by 20% in the St. John's wort group while remaining unchanged in controls. In an earlier study involving 10 clopidogrel-hyporesponsive healthy volunteers, 2 weeks of St. John's wort at 300 mg thrice daily boosted platelet inhibition by 36%.

St. John's wort's effects on the cytochrome P450 isoenzyme could in theory affect the metabolism of certain other drugs commonly prescribed in patients with coronary disease. Dr. Lau said that he and his colleagues have demonstrated that, reassuringly, the herbal therapy does not affect LDL levels in patients on statins. However, further prospective randomized studies are clearly needed to firmly establish the safety and efficacy of St. John's wort in converting clopidogrel nonresponders to responders, he added.

In an interview, Dr. Lau said the lack of effective Food and Drug Administration oversight of herbal therapies makes him feel compelled to test every lot of St. John's wort with which he works. He has found, as have others, that concentrations of the active agent often are not as labeled and vary widely from batch to batch with some manufacturers. He has settled on the German Kira brand for its consistency.

Dr. Lau disclosed having no financial interests relevant to this study.

Major Finding: Earlier bedtime predicted significantly higher scores at age 4 years on receptive language, literacy, phonologic awareness, and early math, but not expressive language.

Data Source: An analysis of 8,000 children from the landmark Department of Education–sponsored Early Childhood Longitudinal Study–Birth Cohort.

Disclosures: Dr. Gaylor reported having no financial conflicts in connection with the study.

SAN ANTONIO – Parental emphasis on a consistent bedtime emerged as the strongest predictor of favorable developmental outcomes at 4 years of age in an 8,000-child study.

“Getting parents to set bedtime routines can be an important way to make a significant impact on children's emergent literacy and language skills. Pediatricians can easily promote regular bedtimes with parents and children, behaviors which in turn lead to healthy sleep,” Erika E. Gaylor, Ph.D., said at the meeting.

Preschoolers who averaged fewer than the 11-12 hours of total sleep per 24-hour cycle, recommended in guidelines by the American Academy of Sleep Medicine and other major groups, had significantly lower test scores on language, early math, and literacy skills, reported Dr. Gaylor, an early childhood researcher at SRI International, an independent, nonprofit research and development organization based in Menlo Park, Calif.

Of note, the average nighttime sleep duration of the preschoolers included in this analysis from the landmark Department of Education–sponsored Early Childhood Longitudinal Study–Birth Cohort was 10.5 hours. And since other studies have shown only one-quarter of 4-year-olds still take a daytime nap, that means most U.S. preschoolers are getting 1-2 fewer hours of sleep per 24 hours than recommended.

The analysis was based on a nationally representative sample comprising 8,000 children who underwent standardized, structured assessments of cognition, attention, and emotional development at age 4 years, along with parental phone interviews conducted when the children were aged 9 months and again at 4 years.

Among the key findings:

▸ Three-quarters of children went to bed between 8 and 10 p.m., 22% had a bedtime of 10 p.m. or later, and 3% regularly hit the sack before 8 p.m.

▸ Sixty percent of children woke up between 7 and 9 a.m. Thirty-two percent regularly awakened before 7 a.m.

▸ Children from higher socioeconomic status households went to bed significantly earlier and were 36% more likely to have a rule about bedtime.

▸ African American children went to bed an average of a quarter hour later than did white children and slept significantly less during the night.

▸ Earlier bedtime predicted significantly higher scores at age 4 years on receptive language, literacy, phonologic awareness, and early math, but not expressive language.

Dr. Gaylor noted that this is the largest study of its kind. Its chief limitation was that it relied on parental reports of children's sleep duration, she said.

Major Finding: Earlier bedtime predicted significantly higher scores at age 4 years on receptive language, literacy, phonologic awareness, and early math, but not expressive language.

Data Source: An analysis of 8,000 children from the landmark Department of Education–sponsored Early Childhood Longitudinal Study–Birth Cohort.

Disclosures: Dr. Gaylor reported having no financial conflicts in connection with the study.

SAN ANTONIO – Parental emphasis on a consistent bedtime emerged as the strongest predictor of favorable developmental outcomes at 4 years of age in an 8,000-child study.

“Getting parents to set bedtime routines can be an important way to make a significant impact on children's emergent literacy and language skills. Pediatricians can easily promote regular bedtimes with parents and children, behaviors which in turn lead to healthy sleep,” Erika E. Gaylor, Ph.D., said at the meeting.

Preschoolers who averaged fewer than the 11-12 hours of total sleep per 24-hour cycle, recommended in guidelines by the American Academy of Sleep Medicine and other major groups, had significantly lower test scores on language, early math, and literacy skills, reported Dr. Gaylor, an early childhood researcher at SRI International, an independent, nonprofit research and development organization based in Menlo Park, Calif.

Of note, the average nighttime sleep duration of the preschoolers included in this analysis from the landmark Department of Education–sponsored Early Childhood Longitudinal Study–Birth Cohort was 10.5 hours. And since other studies have shown only one-quarter of 4-year-olds still take a daytime nap, that means most U.S. preschoolers are getting 1-2 fewer hours of sleep per 24 hours than recommended.

The analysis was based on a nationally representative sample comprising 8,000 children who underwent standardized, structured assessments of cognition, attention, and emotional development at age 4 years, along with parental phone interviews conducted when the children were aged 9 months and again at 4 years.

Among the key findings:

▸ Three-quarters of children went to bed between 8 and 10 p.m., 22% had a bedtime of 10 p.m. or later, and 3% regularly hit the sack before 8 p.m.

▸ Sixty percent of children woke up between 7 and 9 a.m. Thirty-two percent regularly awakened before 7 a.m.

▸ Children from higher socioeconomic status households went to bed significantly earlier and were 36% more likely to have a rule about bedtime.

▸ African American children went to bed an average of a quarter hour later than did white children and slept significantly less during the night.

▸ Earlier bedtime predicted significantly higher scores at age 4 years on receptive language, literacy, phonologic awareness, and early math, but not expressive language.

Dr. Gaylor noted that this is the largest study of its kind. Its chief limitation was that it relied on parental reports of children's sleep duration, she said.

Major Finding: Earlier bedtime predicted significantly higher scores at age 4 years on receptive language, literacy, phonologic awareness, and early math, but not expressive language.

Data Source: An analysis of 8,000 children from the landmark Department of Education–sponsored Early Childhood Longitudinal Study–Birth Cohort.

Disclosures: Dr. Gaylor reported having no financial conflicts in connection with the study.

SAN ANTONIO – Parental emphasis on a consistent bedtime emerged as the strongest predictor of favorable developmental outcomes at 4 years of age in an 8,000-child study.

“Getting parents to set bedtime routines can be an important way to make a significant impact on children's emergent literacy and language skills. Pediatricians can easily promote regular bedtimes with parents and children, behaviors which in turn lead to healthy sleep,” Erika E. Gaylor, Ph.D., said at the meeting.

Preschoolers who averaged fewer than the 11-12 hours of total sleep per 24-hour cycle, recommended in guidelines by the American Academy of Sleep Medicine and other major groups, had significantly lower test scores on language, early math, and literacy skills, reported Dr. Gaylor, an early childhood researcher at SRI International, an independent, nonprofit research and development organization based in Menlo Park, Calif.

Of note, the average nighttime sleep duration of the preschoolers included in this analysis from the landmark Department of Education–sponsored Early Childhood Longitudinal Study–Birth Cohort was 10.5 hours. And since other studies have shown only one-quarter of 4-year-olds still take a daytime nap, that means most U.S. preschoolers are getting 1-2 fewer hours of sleep per 24 hours than recommended.

The analysis was based on a nationally representative sample comprising 8,000 children who underwent standardized, structured assessments of cognition, attention, and emotional development at age 4 years, along with parental phone interviews conducted when the children were aged 9 months and again at 4 years.

Among the key findings:

▸ Three-quarters of children went to bed between 8 and 10 p.m., 22% had a bedtime of 10 p.m. or later, and 3% regularly hit the sack before 8 p.m.

▸ Sixty percent of children woke up between 7 and 9 a.m. Thirty-two percent regularly awakened before 7 a.m.

▸ Children from higher socioeconomic status households went to bed significantly earlier and were 36% more likely to have a rule about bedtime.

▸ African American children went to bed an average of a quarter hour later than did white children and slept significantly less during the night.

▸ Earlier bedtime predicted significantly higher scores at age 4 years on receptive language, literacy, phonologic awareness, and early math, but not expressive language.

Dr. Gaylor noted that this is the largest study of its kind. Its chief limitation was that it relied on parental reports of children's sleep duration, she said.

KEYSTONE, COLO. – Two common comorbidities in type 1 diabetic adolescents are depression and the eating disorder popularly known as diabulimia. Both feature high and upwardly trending hemoglobin A_1c levels, often accompanied by weight loss. But a couple of simple questions can help a clinician readily distinguish between the two.

These questions probe for distortions in body image and eating behavior, two core features of bulimia as described in the DSM-IV. These also are central to diabulimia, but diabulimia isn't a DSM-IV diagnosis and thus does not have formal diagnostic criteria, Grace Shih explained at the conference, sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver.

A couple of years ago, international experts met in Minneapolis and declared the preferred term for diabulimia is “eating disorder in diabetes mellitus type 1,” abbreviated ED-DMT1. However, “diabulimia” has caught on with patients, families, and the mass media, and Ms. Shih generally stuck with that term in her presentation. Also, because the male:female ratio in diabulimia is 1:10, the same as in patients with DSM-IV eating disorders, Ms. Shih often used “she” in referring to diabulimic teens.

The first question to ask a type 1 diabetic adolescent to learn whether she has a distorted body image is, “How much do you weigh?” The clinician already knows the answer, of course: It's right there in the front of the chart. The question's real purpose is to gain insight into the patient's perception of her weight.

A depressed diabetic teen will often answer, “I don't know my weight, and I don't care.” In contrast, diabulimic patients weigh themselves often. Very often. They may take issue with the accuracy of the clinic scale, according to Ms. Shih, a registered dietician at Packard Children's Hospital at Stanford (Calif.) Medical Center with a practice consisting primarily of type 1 diabetic children and adolescents with eating disorders.

The second question to ask is, “What do you think you should weigh?” The depressed patient may answer, “I don't know – whatever.” But not so with the patient with diabulimia.

“The patients with eating disorders will always say something less than their current weight. They could be thin as a rail, but they see themselves as fat,” she continued.

Diabulimic teens also are somewhat obsessive and compulsive about their eating behavior. They restrict fats and sweets, go on frequent diets, and often feel guilty after eating. And they're exceptionally good at calorie counting. Ask a simple question like, “How many calories are there in an apple?” and the response might be, “How big is the diameter of the apple?”

Depressed diabetic teens, on the other hand, will often eat anything, but in very small quantities. “A bite of chips, a bite of hamburger, a bite of chocolate – that's how they eat,” Ms. Shih said.

Roughly 25% of adolescents with type 1 diabetes have comorbid depression. The prevalence of ED-DMT1 is 11%-30%, depending on the study.

Diabulimia has serious health consequences. Japanese investigators reported that a cohort of type 1 diabetic patients took an average of 11.5 and 15.9 years to develop simple and advanced retinopathy, compared with 3.4 and 7.6 years, respectively, in diabulimic patients. Time to diagnosis of nephropathy averaged 15.1 years in type 1 diabetic patients without diabulimia vs. 6.6 years in those with the eating disorder.

“It's scary, isn't it? But don't try to use this information to scare the teenagers. I've tried. It didn't work,” she said. “Inside a teenager's mind, it's as easy as 1+1=2. Insulin equals weight gain, therefore insulin shots equal fat shots. And no insulin equals weight loss.”

Clinicians with a special interest in ED-DMT1 have adapted the DSM-IV criteria for bulimia, which center on binge eating and “inappropriate compensatory behavior” on at least two occasions per week for 3 months. This compensatory behavior might be purging, misuse of laxatives, or excessive exercise, but in diabulimic patients it takes the form of a greater than 25% reduction in insulin dose for more than 3 months for the purpose of weight loss.

If a patient's blood glucose is in excess of 250 mg/dL, the weight loss can be significant, since the renal threshold for glucose is 160-180 mg/dL.

Ms. Shih cautioned that teens often cheat on their blood glucose records to hide the fact that they're not taking insulin. They may provide recordings of dilute orange juice or dog's blood, but the most common way to cheat is to poke a finger and take a blood sample while running the finger under the faucet.

“This is not a group of bad kids,” she stressed. “This is a group of very smart kids. They are just too smart for their own good.”

Once a clinician suspects a patient has diabulimia, it's time to get skilled professional help from a team consisting of an endocrinologist or nurse practitioner, a dietician experienced in treating patients with eating disorders, and a psychotherapist skilled in treating diabulimic patients.

Finding such a team can be difficult. Ms. Shih has three private practice clinics throughout the San Francisco Bay Area, so she knows most local psychotherapists. Many are comfortable treating eating disorders. Few are comfortable in situations where type 1 diabetes is integral to the psychopathology. Exactly the opposite is true among dieticians: Many are highly skilled at diabetes management but don't have the passion or background to take on youths with comorbid eating disorders.

On her Web site (www.gracenutrition.org

Her own treatment approach involves taking the time to get to know the diabulimic patient and figuring out that individual's potential motivator for change. To the young person who is an academic overachiever eager to get into a top university, Ms. Shih might point out that taking her insulin as directed would bring more energy, a better attention span, fewer headaches – and better grades. For the athlete, the appeal might be the prospect of loss of lean body mass because of uncontrolled diabetes.

To the patient with blurred vision caused by swelling of the lens because of osmotic changes induced by very high blood glucose levels, it might be the argument that her eyesight changes, unlike retinopathy, are reversible with improved diabetes control.

“Most of these patients don't take insulin at all, so set small goals and start slow,” the dietician advised.

Ms. Shih disclosed having no conflicts of interest.

Diabulimic patients weigh themselves often and may take issue with the accuracy of the clinic scale.

Source MS. SHIH

KEYSTONE, COLO. – Two common comorbidities in type 1 diabetic adolescents are depression and the eating disorder popularly known as diabulimia. Both feature high and upwardly trending hemoglobin A_1c levels, often accompanied by weight loss. But a couple of simple questions can help a clinician readily distinguish between the two.

These questions probe for distortions in body image and eating behavior, two core features of bulimia as described in the DSM-IV. These also are central to diabulimia, but diabulimia isn't a DSM-IV diagnosis and thus does not have formal diagnostic criteria, Grace Shih explained at the conference, sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver.

A couple of years ago, international experts met in Minneapolis and declared the preferred term for diabulimia is “eating disorder in diabetes mellitus type 1,” abbreviated ED-DMT1. However, “diabulimia” has caught on with patients, families, and the mass media, and Ms. Shih generally stuck with that term in her presentation. Also, because the male:female ratio in diabulimia is 1:10, the same as in patients with DSM-IV eating disorders, Ms. Shih often used “she” in referring to diabulimic teens.

The first question to ask a type 1 diabetic adolescent to learn whether she has a distorted body image is, “How much do you weigh?” The clinician already knows the answer, of course: It's right there in the front of the chart. The question's real purpose is to gain insight into the patient's perception of her weight.

A depressed diabetic teen will often answer, “I don't know my weight, and I don't care.” In contrast, diabulimic patients weigh themselves often. Very often. They may take issue with the accuracy of the clinic scale, according to Ms. Shih, a registered dietician at Packard Children's Hospital at Stanford (Calif.) Medical Center with a practice consisting primarily of type 1 diabetic children and adolescents with eating disorders.

The second question to ask is, “What do you think you should weigh?” The depressed patient may answer, “I don't know – whatever.” But not so with the patient with diabulimia.

“The patients with eating disorders will always say something less than their current weight. They could be thin as a rail, but they see themselves as fat,” she continued.

Diabulimic teens also are somewhat obsessive and compulsive about their eating behavior. They restrict fats and sweets, go on frequent diets, and often feel guilty after eating. And they're exceptionally good at calorie counting. Ask a simple question like, “How many calories are there in an apple?” and the response might be, “How big is the diameter of the apple?”

Depressed diabetic teens, on the other hand, will often eat anything, but in very small quantities. “A bite of chips, a bite of hamburger, a bite of chocolate – that's how they eat,” Ms. Shih said.

Roughly 25% of adolescents with type 1 diabetes have comorbid depression. The prevalence of ED-DMT1 is 11%-30%, depending on the study.

Diabulimia has serious health consequences. Japanese investigators reported that a cohort of type 1 diabetic patients took an average of 11.5 and 15.9 years to develop simple and advanced retinopathy, compared with 3.4 and 7.6 years, respectively, in diabulimic patients. Time to diagnosis of nephropathy averaged 15.1 years in type 1 diabetic patients without diabulimia vs. 6.6 years in those with the eating disorder.

“It's scary, isn't it? But don't try to use this information to scare the teenagers. I've tried. It didn't work,” she said. “Inside a teenager's mind, it's as easy as 1+1=2. Insulin equals weight gain, therefore insulin shots equal fat shots. And no insulin equals weight loss.”

Clinicians with a special interest in ED-DMT1 have adapted the DSM-IV criteria for bulimia, which center on binge eating and “inappropriate compensatory behavior” on at least two occasions per week for 3 months. This compensatory behavior might be purging, misuse of laxatives, or excessive exercise, but in diabulimic patients it takes the form of a greater than 25% reduction in insulin dose for more than 3 months for the purpose of weight loss.

If a patient's blood glucose is in excess of 250 mg/dL, the weight loss can be significant, since the renal threshold for glucose is 160-180 mg/dL.

Ms. Shih cautioned that teens often cheat on their blood glucose records to hide the fact that they're not taking insulin. They may provide recordings of dilute orange juice or dog's blood, but the most common way to cheat is to poke a finger and take a blood sample while running the finger under the faucet.

“This is not a group of bad kids,” she stressed. “This is a group of very smart kids. They are just too smart for their own good.”

Once a clinician suspects a patient has diabulimia, it's time to get skilled professional help from a team consisting of an endocrinologist or nurse practitioner, a dietician experienced in treating patients with eating disorders, and a psychotherapist skilled in treating diabulimic patients.

Finding such a team can be difficult. Ms. Shih has three private practice clinics throughout the San Francisco Bay Area, so she knows most local psychotherapists. Many are comfortable treating eating disorders. Few are comfortable in situations where type 1 diabetes is integral to the psychopathology. Exactly the opposite is true among dieticians: Many are highly skilled at diabetes management but don't have the passion or background to take on youths with comorbid eating disorders.

On her Web site (www.gracenutrition.org

Her own treatment approach involves taking the time to get to know the diabulimic patient and figuring out that individual's potential motivator for change. To the young person who is an academic overachiever eager to get into a top university, Ms. Shih might point out that taking her insulin as directed would bring more energy, a better attention span, fewer headaches – and better grades. For the athlete, the appeal might be the prospect of loss of lean body mass because of uncontrolled diabetes.

To the patient with blurred vision caused by swelling of the lens because of osmotic changes induced by very high blood glucose levels, it might be the argument that her eyesight changes, unlike retinopathy, are reversible with improved diabetes control.

“Most of these patients don't take insulin at all, so set small goals and start slow,” the dietician advised.

Ms. Shih disclosed having no conflicts of interest.

Diabulimic patients weigh themselves often and may take issue with the accuracy of the clinic scale.

Source MS. SHIH

KEYSTONE, COLO. – Two common comorbidities in type 1 diabetic adolescents are depression and the eating disorder popularly known as diabulimia. Both feature high and upwardly trending hemoglobin A_1c levels, often accompanied by weight loss. But a couple of simple questions can help a clinician readily distinguish between the two.

These questions probe for distortions in body image and eating behavior, two core features of bulimia as described in the DSM-IV. These also are central to diabulimia, but diabulimia isn't a DSM-IV diagnosis and thus does not have formal diagnostic criteria, Grace Shih explained at the conference, sponsored by the University of Colorado, Denver, and the Children's Diabetes Foundation at Denver.

A couple of years ago, international experts met in Minneapolis and declared the preferred term for diabulimia is “eating disorder in diabetes mellitus type 1,” abbreviated ED-DMT1. However, “diabulimia” has caught on with patients, families, and the mass media, and Ms. Shih generally stuck with that term in her presentation. Also, because the male:female ratio in diabulimia is 1:10, the same as in patients with DSM-IV eating disorders, Ms. Shih often used “she” in referring to diabulimic teens.

The first question to ask a type 1 diabetic adolescent to learn whether she has a distorted body image is, “How much do you weigh?” The clinician already knows the answer, of course: It's right there in the front of the chart. The question's real purpose is to gain insight into the patient's perception of her weight.

A depressed diabetic teen will often answer, “I don't know my weight, and I don't care.” In contrast, diabulimic patients weigh themselves often. Very often. They may take issue with the accuracy of the clinic scale, according to Ms. Shih, a registered dietician at Packard Children's Hospital at Stanford (Calif.) Medical Center with a practice consisting primarily of type 1 diabetic children and adolescents with eating disorders.

The second question to ask is, “What do you think you should weigh?” The depressed patient may answer, “I don't know – whatever.” But not so with the patient with diabulimia.

“The patients with eating disorders will always say something less than their current weight. They could be thin as a rail, but they see themselves as fat,” she continued.

Diabulimic teens also are somewhat obsessive and compulsive about their eating behavior. They restrict fats and sweets, go on frequent diets, and often feel guilty after eating. And they're exceptionally good at calorie counting. Ask a simple question like, “How many calories are there in an apple?” and the response might be, “How big is the diameter of the apple?”

Depressed diabetic teens, on the other hand, will often eat anything, but in very small quantities. “A bite of chips, a bite of hamburger, a bite of chocolate – that's how they eat,” Ms. Shih said.

Roughly 25% of adolescents with type 1 diabetes have comorbid depression. The prevalence of ED-DMT1 is 11%-30%, depending on the study.

Diabulimia has serious health consequences. Japanese investigators reported that a cohort of type 1 diabetic patients took an average of 11.5 and 15.9 years to develop simple and advanced retinopathy, compared with 3.4 and 7.6 years, respectively, in diabulimic patients. Time to diagnosis of nephropathy averaged 15.1 years in type 1 diabetic patients without diabulimia vs. 6.6 years in those with the eating disorder.

“It's scary, isn't it? But don't try to use this information to scare the teenagers. I've tried. It didn't work,” she said. “Inside a teenager's mind, it's as easy as 1+1=2. Insulin equals weight gain, therefore insulin shots equal fat shots. And no insulin equals weight loss.”

Clinicians with a special interest in ED-DMT1 have adapted the DSM-IV criteria for bulimia, which center on binge eating and “inappropriate compensatory behavior” on at least two occasions per week for 3 months. This compensatory behavior might be purging, misuse of laxatives, or excessive exercise, but in diabulimic patients it takes the form of a greater than 25% reduction in insulin dose for more than 3 months for the purpose of weight loss.

If a patient's blood glucose is in excess of 250 mg/dL, the weight loss can be significant, since the renal threshold for glucose is 160-180 mg/dL.

Ms. Shih cautioned that teens often cheat on their blood glucose records to hide the fact that they're not taking insulin. They may provide recordings of dilute orange juice or dog's blood, but the most common way to cheat is to poke a finger and take a blood sample while running the finger under the faucet.

“This is not a group of bad kids,” she stressed. “This is a group of very smart kids. They are just too smart for their own good.”

Once a clinician suspects a patient has diabulimia, it's time to get skilled professional help from a team consisting of an endocrinologist or nurse practitioner, a dietician experienced in treating patients with eating disorders, and a psychotherapist skilled in treating diabulimic patients.

Finding such a team can be difficult. Ms. Shih has three private practice clinics throughout the San Francisco Bay Area, so she knows most local psychotherapists. Many are comfortable treating eating disorders. Few are comfortable in situations where type 1 diabetes is integral to the psychopathology. Exactly the opposite is true among dieticians: Many are highly skilled at diabetes management but don't have the passion or background to take on youths with comorbid eating disorders.

On her Web site (www.gracenutrition.org

Her own treatment approach involves taking the time to get to know the diabulimic patient and figuring out that individual's potential motivator for change. To the young person who is an academic overachiever eager to get into a top university, Ms. Shih might point out that taking her insulin as directed would bring more energy, a better attention span, fewer headaches – and better grades. For the athlete, the appeal might be the prospect of loss of lean body mass because of uncontrolled diabetes.

To the patient with blurred vision caused by swelling of the lens because of osmotic changes induced by very high blood glucose levels, it might be the argument that her eyesight changes, unlike retinopathy, are reversible with improved diabetes control.

“Most of these patients don't take insulin at all, so set small goals and start slow,” the dietician advised.

Ms. Shih disclosed having no conflicts of interest.

Diabulimic patients weigh themselves often and may take issue with the accuracy of the clinic scale.

Source MS. SHIH

EDINBURGH – Long-term combination therapy with lithium plus valproate in patients with bipolar I disorder proved to be markedly more effective than valproate monotherapy in the randomized BALANCE trial.

BALANCE (Bipolar Affective Disorder: Lithium Anticonvulsant Evaluation) will be a practice-changing study, both in the United States and in the United Kingdom, where it originated, study coordinator and chief investigator Dr. John R. Geddes predicted at the congress.

“As valproate monotherapy is substantially the most commonly used treatment in the United States, BALANCE should probably lead to some change in practice over there. …. I think BALANCE would suggest that for a majority of patients, combination therapy would be a better bet than valproate monotherapy. And even lithium might be better as a first-line therapy,” commented Dr. Geddes, professor of epidemiological psychiatry and a senior clinical research fellow at the University of Oxford (England).

BALANCE included 330 patients aged 16 and older with bipolar I disorder at 41 sites in the United Kingdom, France, the United States, and Italy who were randomized to open-label lithium monotherapy at a target dose of 0.4-1.0 mmol/L, valproate monotherapy at 750-1,250 mg/day, or both agents in combination.

The primary outcome was emergence of a new mood episode requiring further intervention (defined as either another medication or hospitalization) during 2 years of follow-up. This occurred in 69% of the valproate group, 59% of those taking lithium, and 54% on combination therapy (Lancet 2010;375:385-95).

Thus, combination therapy resulted in a 41% relative risk reduction in the primary end point compared with valproate monotherapy, and an 18% reduction compared with lithium. Lithium monotherapy achieved a 39% relative risk reduction compared with valproate.

The time to a 10% hospitalization rate averaged 4.7 months in the valproate group, 7.7 months with lithium, and 11.3 months with combination therapy.

“You may well want to put patients on combination therapy before they've had the chance to fail on monotherapy, in the same way that in cancer therapy we often use combination therapy right from day 1. It really gives you the best chance of controlling the condition,” he said.

In terms of numbers needed to treat (NNT), BALANCE showed that seven bipolar patients would need to receive combination therapy for 2 years instead of valproate in order for there to be one fewer relapse; that's a very favorable NNT, Dr. Geddes observed. The NNT was 10 for lithium vs. valproate, and 20 for combination therapy vs. lithium monotherapy.

“We can neither refute nor confirm an added benefit for combination therapy over lithium alone,” Dr. Geddes said. “The trial would have to be quite a lot larger to pick up any added benefit.”

No baseline predictors of individual treatment response could be identified. Genotype data are now being analyzed. “The results so far aren't overly impressive, so don't hold your breath on that one,” he advised.

Lithium proved to be better than valproate for prevention of depressive as well as manic relapses in BALANCE, contrary to the conventional wisdom that holds that valproate is the more effective agent against depressive symptoms. However, this finding is consistent with the results of a recent meta-analysis by Dr. Geddes and his colleagues, which he said showed “quite convincingly” that lithium was more effective than valproate in preventing depressive symptoms.

The BALANCE trial was funded by the Stanley Medical Research Institute, with donation of drugs by Sanofi-Aventis. Dr. Geddes disclosed having received research funds from the Medical Research Council, the Economic and Social Research Council, and the National Institute for Health Research, as well as the Stanley Medical Research Institute.

EDINBURGH – Long-term combination therapy with lithium plus valproate in patients with bipolar I disorder proved to be markedly more effective than valproate monotherapy in the randomized BALANCE trial.

BALANCE (Bipolar Affective Disorder: Lithium Anticonvulsant Evaluation) will be a practice-changing study, both in the United States and in the United Kingdom, where it originated, study coordinator and chief investigator Dr. John R. Geddes predicted at the congress.

“As valproate monotherapy is substantially the most commonly used treatment in the United States, BALANCE should probably lead to some change in practice over there. …. I think BALANCE would suggest that for a majority of patients, combination therapy would be a better bet than valproate monotherapy. And even lithium might be better as a first-line therapy,” commented Dr. Geddes, professor of epidemiological psychiatry and a senior clinical research fellow at the University of Oxford (England).

BALANCE included 330 patients aged 16 and older with bipolar I disorder at 41 sites in the United Kingdom, France, the United States, and Italy who were randomized to open-label lithium monotherapy at a target dose of 0.4-1.0 mmol/L, valproate monotherapy at 750-1,250 mg/day, or both agents in combination.

The primary outcome was emergence of a new mood episode requiring further intervention (defined as either another medication or hospitalization) during 2 years of follow-up. This occurred in 69% of the valproate group, 59% of those taking lithium, and 54% on combination therapy (Lancet 2010;375:385-95).

Thus, combination therapy resulted in a 41% relative risk reduction in the primary end point compared with valproate monotherapy, and an 18% reduction compared with lithium. Lithium monotherapy achieved a 39% relative risk reduction compared with valproate.

The time to a 10% hospitalization rate averaged 4.7 months in the valproate group, 7.7 months with lithium, and 11.3 months with combination therapy.

“You may well want to put patients on combination therapy before they've had the chance to fail on monotherapy, in the same way that in cancer therapy we often use combination therapy right from day 1. It really gives you the best chance of controlling the condition,” he said.

In terms of numbers needed to treat (NNT), BALANCE showed that seven bipolar patients would need to receive combination therapy for 2 years instead of valproate in order for there to be one fewer relapse; that's a very favorable NNT, Dr. Geddes observed. The NNT was 10 for lithium vs. valproate, and 20 for combination therapy vs. lithium monotherapy.

“We can neither refute nor confirm an added benefit for combination therapy over lithium alone,” Dr. Geddes said. “The trial would have to be quite a lot larger to pick up any added benefit.”

No baseline predictors of individual treatment response could be identified. Genotype data are now being analyzed. “The results so far aren't overly impressive, so don't hold your breath on that one,” he advised.

Lithium proved to be better than valproate for prevention of depressive as well as manic relapses in BALANCE, contrary to the conventional wisdom that holds that valproate is the more effective agent against depressive symptoms. However, this finding is consistent with the results of a recent meta-analysis by Dr. Geddes and his colleagues, which he said showed “quite convincingly” that lithium was more effective than valproate in preventing depressive symptoms.

The BALANCE trial was funded by the Stanley Medical Research Institute, with donation of drugs by Sanofi-Aventis. Dr. Geddes disclosed having received research funds from the Medical Research Council, the Economic and Social Research Council, and the National Institute for Health Research, as well as the Stanley Medical Research Institute.

EDINBURGH – Long-term combination therapy with lithium plus valproate in patients with bipolar I disorder proved to be markedly more effective than valproate monotherapy in the randomized BALANCE trial.

BALANCE (Bipolar Affective Disorder: Lithium Anticonvulsant Evaluation) will be a practice-changing study, both in the United States and in the United Kingdom, where it originated, study coordinator and chief investigator Dr. John R. Geddes predicted at the congress.

“As valproate monotherapy is substantially the most commonly used treatment in the United States, BALANCE should probably lead to some change in practice over there. …. I think BALANCE would suggest that for a majority of patients, combination therapy would be a better bet than valproate monotherapy. And even lithium might be better as a first-line therapy,” commented Dr. Geddes, professor of epidemiological psychiatry and a senior clinical research fellow at the University of Oxford (England).

BALANCE included 330 patients aged 16 and older with bipolar I disorder at 41 sites in the United Kingdom, France, the United States, and Italy who were randomized to open-label lithium monotherapy at a target dose of 0.4-1.0 mmol/L, valproate monotherapy at 750-1,250 mg/day, or both agents in combination.

The primary outcome was emergence of a new mood episode requiring further intervention (defined as either another medication or hospitalization) during 2 years of follow-up. This occurred in 69% of the valproate group, 59% of those taking lithium, and 54% on combination therapy (Lancet 2010;375:385-95).

Thus, combination therapy resulted in a 41% relative risk reduction in the primary end point compared with valproate monotherapy, and an 18% reduction compared with lithium. Lithium monotherapy achieved a 39% relative risk reduction compared with valproate.

The time to a 10% hospitalization rate averaged 4.7 months in the valproate group, 7.7 months with lithium, and 11.3 months with combination therapy.

“You may well want to put patients on combination therapy before they've had the chance to fail on monotherapy, in the same way that in cancer therapy we often use combination therapy right from day 1. It really gives you the best chance of controlling the condition,” he said.

In terms of numbers needed to treat (NNT), BALANCE showed that seven bipolar patients would need to receive combination therapy for 2 years instead of valproate in order for there to be one fewer relapse; that's a very favorable NNT, Dr. Geddes observed. The NNT was 10 for lithium vs. valproate, and 20 for combination therapy vs. lithium monotherapy.

“We can neither refute nor confirm an added benefit for combination therapy over lithium alone,” Dr. Geddes said. “The trial would have to be quite a lot larger to pick up any added benefit.”

No baseline predictors of individual treatment response could be identified. Genotype data are now being analyzed. “The results so far aren't overly impressive, so don't hold your breath on that one,” he advised.

Lithium proved to be better than valproate for prevention of depressive as well as manic relapses in BALANCE, contrary to the conventional wisdom that holds that valproate is the more effective agent against depressive symptoms. However, this finding is consistent with the results of a recent meta-analysis by Dr. Geddes and his colleagues, which he said showed “quite convincingly” that lithium was more effective than valproate in preventing depressive symptoms.

The BALANCE trial was funded by the Stanley Medical Research Institute, with donation of drugs by Sanofi-Aventis. Dr. Geddes disclosed having received research funds from the Medical Research Council, the Economic and Social Research Council, and the National Institute for Health Research, as well as the Stanley Medical Research Institute.

GOTHENBURG, SWEDEN – Botulinum toxin injections to the soles of the feet are a highly effective, safe, and long-lasting treatment for painful blistering and calluses in patients with sweat-exacerbated epidermolytic keratinopathies, according to Dr. Anders Vahlquist said at the annual congress of the European Academy of Dermatology and Venereology.

The same technique is also beneficial in patients with acantholytic disorders aggravated by sweat and friction, such as the intertriginous erosive lesions of Hailey-Hailey disease or Darier disease, said Dr. Vahlquist at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Vahlquist, a professor of dermatology at Uppsala (Sweden) University, and colleagues introduced plantar botulinum toxin injections as a novel treatment for sweat-exacerbated severe foot problems caused by epidermolytic keratinopathies more than 4 years (Br. J. Dermatol. 2006;154:763-5).

At the EADV congress, he presented his updated experience with the therapy in six patients with epidermolysis bullosa simplex and eight with pachyonychia congenita ranging in age from 7 to 66 years.

These were patients who had considerable difficulty in walking, especially during warm weather, because foot sweat worsened their plantar blistering at pressure sites, said Dr. Vahlquist. The patients received a mean of 5.6 treatment sessions, each entailing multiple injections of botulinum toxin type A or B to the soles of the feet administered under intravenous regional or general anesthesia.

Thirteen of the 14 patients reported what Dr. Vahlquist described as "remarkable" relief of pain within a week. The mean duration of benefit patients reported was 3 months. Because the foot symptoms were most problematic during the warm weather months, most patients did well with one or two treatment sessions per year. This is good news because the anesthesia requirement – essential because the soles are so sensitive – makes this an expensive therapy, he noted.

Seven of the eight patients with pachyonychia congenita and five of six with epidermolysis bullosa simplex rated their condition as either "very much" or "a lot" improved after treatment.

Dr. Vahlquist noted that physicians at Roger Williams Medical Center in Providence, R.I., have also reported that botulinum toxin injections to the soles of the feet are effective for patients with epidermolysis bullosa simplex (Arch. Dermatol. 2009;145:13-5).

"With this confirmatory study in the United States, we hope that this therapy will see greater use. It would be a help to many patients while we wait for the curative therapy that’s hopefully to come," he said.

Dr. Vahlquist said he has also used this therapy in 10 patients with Hailey-Hailey disease featuring sweat-exacerbated painful erosive lesions in the groin and other intertriginous areas. He termed the results of this chemical denervation of the sweat glands in the targeted areas "very promising."

A Swiss dermatologist from Bern rose from the audience to confirm the benefit of botulinum toxin in patients with Hailey-Hailey disease. He and his colleagues have treated a dozen such patients with what he described as "really impressive" outcomes. "The results are fantastic," he said. "These patients are born again. They are really very, very happy."

Dr. Vahlquist reporting having no relevant financial interests.

GOTHENBURG, SWEDEN – Botulinum toxin injections to the soles of the feet are a highly effective, safe, and long-lasting treatment for painful blistering and calluses in patients with sweat-exacerbated epidermolytic keratinopathies, according to Dr. Anders Vahlquist said at the annual congress of the European Academy of Dermatology and Venereology.

The same technique is also beneficial in patients with acantholytic disorders aggravated by sweat and friction, such as the intertriginous erosive lesions of Hailey-Hailey disease or Darier disease, said Dr. Vahlquist at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Vahlquist, a professor of dermatology at Uppsala (Sweden) University, and colleagues introduced plantar botulinum toxin injections as a novel treatment for sweat-exacerbated severe foot problems caused by epidermolytic keratinopathies more than 4 years (Br. J. Dermatol. 2006;154:763-5).

At the EADV congress, he presented his updated experience with the therapy in six patients with epidermolysis bullosa simplex and eight with pachyonychia congenita ranging in age from 7 to 66 years.

These were patients who had considerable difficulty in walking, especially during warm weather, because foot sweat worsened their plantar blistering at pressure sites, said Dr. Vahlquist. The patients received a mean of 5.6 treatment sessions, each entailing multiple injections of botulinum toxin type A or B to the soles of the feet administered under intravenous regional or general anesthesia.

Thirteen of the 14 patients reported what Dr. Vahlquist described as "remarkable" relief of pain within a week. The mean duration of benefit patients reported was 3 months. Because the foot symptoms were most problematic during the warm weather months, most patients did well with one or two treatment sessions per year. This is good news because the anesthesia requirement – essential because the soles are so sensitive – makes this an expensive therapy, he noted.

Seven of the eight patients with pachyonychia congenita and five of six with epidermolysis bullosa simplex rated their condition as either "very much" or "a lot" improved after treatment.

Dr. Vahlquist noted that physicians at Roger Williams Medical Center in Providence, R.I., have also reported that botulinum toxin injections to the soles of the feet are effective for patients with epidermolysis bullosa simplex (Arch. Dermatol. 2009;145:13-5).

"With this confirmatory study in the United States, we hope that this therapy will see greater use. It would be a help to many patients while we wait for the curative therapy that’s hopefully to come," he said.

Dr. Vahlquist said he has also used this therapy in 10 patients with Hailey-Hailey disease featuring sweat-exacerbated painful erosive lesions in the groin and other intertriginous areas. He termed the results of this chemical denervation of the sweat glands in the targeted areas "very promising."

A Swiss dermatologist from Bern rose from the audience to confirm the benefit of botulinum toxin in patients with Hailey-Hailey disease. He and his colleagues have treated a dozen such patients with what he described as "really impressive" outcomes. "The results are fantastic," he said. "These patients are born again. They are really very, very happy."

Dr. Vahlquist reporting having no relevant financial interests.

GOTHENBURG, SWEDEN – Botulinum toxin injections to the soles of the feet are a highly effective, safe, and long-lasting treatment for painful blistering and calluses in patients with sweat-exacerbated epidermolytic keratinopathies, according to Dr. Anders Vahlquist said at the annual congress of the European Academy of Dermatology and Venereology.

The same technique is also beneficial in patients with acantholytic disorders aggravated by sweat and friction, such as the intertriginous erosive lesions of Hailey-Hailey disease or Darier disease, said Dr. Vahlquist at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Vahlquist, a professor of dermatology at Uppsala (Sweden) University, and colleagues introduced plantar botulinum toxin injections as a novel treatment for sweat-exacerbated severe foot problems caused by epidermolytic keratinopathies more than 4 years (Br. J. Dermatol. 2006;154:763-5).

At the EADV congress, he presented his updated experience with the therapy in six patients with epidermolysis bullosa simplex and eight with pachyonychia congenita ranging in age from 7 to 66 years.

These were patients who had considerable difficulty in walking, especially during warm weather, because foot sweat worsened their plantar blistering at pressure sites, said Dr. Vahlquist. The patients received a mean of 5.6 treatment sessions, each entailing multiple injections of botulinum toxin type A or B to the soles of the feet administered under intravenous regional or general anesthesia.

Thirteen of the 14 patients reported what Dr. Vahlquist described as "remarkable" relief of pain within a week. The mean duration of benefit patients reported was 3 months. Because the foot symptoms were most problematic during the warm weather months, most patients did well with one or two treatment sessions per year. This is good news because the anesthesia requirement – essential because the soles are so sensitive – makes this an expensive therapy, he noted.

Seven of the eight patients with pachyonychia congenita and five of six with epidermolysis bullosa simplex rated their condition as either "very much" or "a lot" improved after treatment.

Dr. Vahlquist noted that physicians at Roger Williams Medical Center in Providence, R.I., have also reported that botulinum toxin injections to the soles of the feet are effective for patients with epidermolysis bullosa simplex (Arch. Dermatol. 2009;145:13-5).

"With this confirmatory study in the United States, we hope that this therapy will see greater use. It would be a help to many patients while we wait for the curative therapy that’s hopefully to come," he said.

Dr. Vahlquist said he has also used this therapy in 10 patients with Hailey-Hailey disease featuring sweat-exacerbated painful erosive lesions in the groin and other intertriginous areas. He termed the results of this chemical denervation of the sweat glands in the targeted areas "very promising."

A Swiss dermatologist from Bern rose from the audience to confirm the benefit of botulinum toxin in patients with Hailey-Hailey disease. He and his colleagues have treated a dozen such patients with what he described as "really impressive" outcomes. "The results are fantastic," he said. "These patients are born again. They are really very, very happy."

Dr. Vahlquist reporting having no relevant financial interests.