Michele G. Sullivan

Major Finding: More than half of 427 children with juvenile idiopathic arthritis were not in remission or were in remission but still taking medications, after 98 months of follow-up.

Data Source: A report of 7-year follow-up data on 427 children enrolled in the Nordic Juvenile Idiopathic Arthritis Cohort from 1997–2000.

Disclosures: Neither Dr. Rygg, Dr. Nordal, nor Ms. Hilderson disclosed any potential financial conflicts.

VALENCIA, SPAIN — Despite treatment, nearly half of children with juvenile idiopathic arthritis continue to experience active disease and many report significant physical fatigue, according to researchers.

“Our results point out that JIA is a controllable and treatable, but not curable, disease for a majority of the children,” coauthor Dr. Marite Rygg of St. Olav's Hospital, Trondheim, Norway, said in an interview.

Her colleague, Dr. Ellen Nordal, reported 7-year follow-up data on 427 children who were enrolled in the Nordic Juvenile Idiopathic Arthritis Cohort from 1997–2000. The cohort comprised patients from 12 centers in Norway, Finland, Sweden, and Denmark. At the congress, Dr. Nordal reported complete follow-up data on 427 of the children.

Most the patients (66%) were girls. Their median age at the onset of disease was 6 years. The most common arthritis subtype in the group was oligoarthritis; this was persistent in 126 and extended in 75. Other disease subtypes included polyarthritis (82); psoriatic arthritis (13); enthesitis-related arthritis (49); undifferentiated arthritis (64), and systemic arthritis (18). Uveitis developed in 89 children during the follow-up period.

At baseline, almost all of the children (97%) had taken a nonsteroidal anti-inflammatory drug. About half (48%) had taken methotrexate, while 74% had received intra-articular glucocorticoids and 32% received oral glucocorticoids. More than half (58%) had used a disease-modifying anti-rheumatic drug, including an anti-TNF (anti–tumor necrosis factor) drug. Only 3% were not taking any medications at baseline.

The mean follow-up period was 98 months. By then, 42% were in remission and off medication. However, more than half of the group (58%) were either not in remission (49%) or were in remission on medication (9%) said Dr. Nordal, a pediatric rheumatologist at the University Hospital of North Norway, Tromsø.

Rates of remission off medication varied by subtype, with the greatest rate occurring among those with systemic arthritis (83%). The lowest rates occurred in those with extended oligoarthritis (21%) and psoriatic arthritis (23%).

The highest rates of ongoing disease occurred in those who had rheumatoid factor–positive polyarthritis (67%) and extended oligoarthritis (63%). More than half of children with rheumatoid factor–negative polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis also failed to achieve remission.

Fatigue is another aspect of the disease that affects young people as they grow into their teens, according to registered nurse Deborah Hilderson of the Catholic University of Leuven, Belgium. She presented the results of a small cross-sectional study of 31 adolescents with JIA, which examined the impact of fatigue on their daily lives. The patients were compared with a group of healthy controls used in a 2003 study of excess fatigue in young adult survivors of childhood cancer (Eur. J. Cancer 2003;39:204–14).

The patients had a mean age of 16 years; all had been treated at the University Hospital Leuven (Belgium). Most (23) were female. Persistent or extended oligoarthritis was present in 11 patients; rheumatoid factor–negative polyarthritis in 9; systemic arthritis in 4; and enthesitis-related arthritis in 7.

They completed two quality of life measures. The Multidimensional Fatigue Inventory (MFI) scores fatigue on a 20-point scale in five domains: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. High scores indicate higher fatigue levels. The 100-point Quality of Life Linear Analog Scale rates 100 as the best quality of life imaginable, and 0 the worst.

About 13% of the patients reported a score of 15 or higher in the general fatigue domain of the MFI. There were no significant differences between the disease subtypes for any of the five fatigue domains. Compared with controls, patients reported significantly higher scores for physical fatigue and reduced activity. However, Ms. Hilderson noted, although the differences were statistically significant, the actual differences were “rather small.”

The median quality of life score was 74, but the range was wide (10–97). Higher quality of life scores were significantly associated with lower fatigue scores. There was a moderate association between quality of life and general and mental fatigue, Ms. Hilderson said.

“Fatigue does seem to be a problem for adolescents with JIA, and we, as health care providers, do need to pay attention to this complaint, particularly in patients with active arthritis,” Ms. Hilderson said.

Vitals

Source Elsevier Global Medical News

Major Finding: More than half of 427 children with juvenile idiopathic arthritis were not in remission or were in remission but still taking medications, after 98 months of follow-up.

Data Source: A report of 7-year follow-up data on 427 children enrolled in the Nordic Juvenile Idiopathic Arthritis Cohort from 1997–2000.

Disclosures: Neither Dr. Rygg, Dr. Nordal, nor Ms. Hilderson disclosed any potential financial conflicts.

VALENCIA, SPAIN — Despite treatment, nearly half of children with juvenile idiopathic arthritis continue to experience active disease and many report significant physical fatigue, according to researchers.

“Our results point out that JIA is a controllable and treatable, but not curable, disease for a majority of the children,” coauthor Dr. Marite Rygg of St. Olav's Hospital, Trondheim, Norway, said in an interview.

Her colleague, Dr. Ellen Nordal, reported 7-year follow-up data on 427 children who were enrolled in the Nordic Juvenile Idiopathic Arthritis Cohort from 1997–2000. The cohort comprised patients from 12 centers in Norway, Finland, Sweden, and Denmark. At the congress, Dr. Nordal reported complete follow-up data on 427 of the children.

Most the patients (66%) were girls. Their median age at the onset of disease was 6 years. The most common arthritis subtype in the group was oligoarthritis; this was persistent in 126 and extended in 75. Other disease subtypes included polyarthritis (82); psoriatic arthritis (13); enthesitis-related arthritis (49); undifferentiated arthritis (64), and systemic arthritis (18). Uveitis developed in 89 children during the follow-up period.

At baseline, almost all of the children (97%) had taken a nonsteroidal anti-inflammatory drug. About half (48%) had taken methotrexate, while 74% had received intra-articular glucocorticoids and 32% received oral glucocorticoids. More than half (58%) had used a disease-modifying anti-rheumatic drug, including an anti-TNF (anti–tumor necrosis factor) drug. Only 3% were not taking any medications at baseline.

The mean follow-up period was 98 months. By then, 42% were in remission and off medication. However, more than half of the group (58%) were either not in remission (49%) or were in remission on medication (9%) said Dr. Nordal, a pediatric rheumatologist at the University Hospital of North Norway, Tromsø.

Rates of remission off medication varied by subtype, with the greatest rate occurring among those with systemic arthritis (83%). The lowest rates occurred in those with extended oligoarthritis (21%) and psoriatic arthritis (23%).

The highest rates of ongoing disease occurred in those who had rheumatoid factor–positive polyarthritis (67%) and extended oligoarthritis (63%). More than half of children with rheumatoid factor–negative polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis also failed to achieve remission.

Fatigue is another aspect of the disease that affects young people as they grow into their teens, according to registered nurse Deborah Hilderson of the Catholic University of Leuven, Belgium. She presented the results of a small cross-sectional study of 31 adolescents with JIA, which examined the impact of fatigue on their daily lives. The patients were compared with a group of healthy controls used in a 2003 study of excess fatigue in young adult survivors of childhood cancer (Eur. J. Cancer 2003;39:204–14).

The patients had a mean age of 16 years; all had been treated at the University Hospital Leuven (Belgium). Most (23) were female. Persistent or extended oligoarthritis was present in 11 patients; rheumatoid factor–negative polyarthritis in 9; systemic arthritis in 4; and enthesitis-related arthritis in 7.

They completed two quality of life measures. The Multidimensional Fatigue Inventory (MFI) scores fatigue on a 20-point scale in five domains: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. High scores indicate higher fatigue levels. The 100-point Quality of Life Linear Analog Scale rates 100 as the best quality of life imaginable, and 0 the worst.

About 13% of the patients reported a score of 15 or higher in the general fatigue domain of the MFI. There were no significant differences between the disease subtypes for any of the five fatigue domains. Compared with controls, patients reported significantly higher scores for physical fatigue and reduced activity. However, Ms. Hilderson noted, although the differences were statistically significant, the actual differences were “rather small.”

The median quality of life score was 74, but the range was wide (10–97). Higher quality of life scores were significantly associated with lower fatigue scores. There was a moderate association between quality of life and general and mental fatigue, Ms. Hilderson said.

“Fatigue does seem to be a problem for adolescents with JIA, and we, as health care providers, do need to pay attention to this complaint, particularly in patients with active arthritis,” Ms. Hilderson said.

Vitals

Source Elsevier Global Medical News

Major Finding: More than half of 427 children with juvenile idiopathic arthritis were not in remission or were in remission but still taking medications, after 98 months of follow-up.

Data Source: A report of 7-year follow-up data on 427 children enrolled in the Nordic Juvenile Idiopathic Arthritis Cohort from 1997–2000.

Disclosures: Neither Dr. Rygg, Dr. Nordal, nor Ms. Hilderson disclosed any potential financial conflicts.

VALENCIA, SPAIN — Despite treatment, nearly half of children with juvenile idiopathic arthritis continue to experience active disease and many report significant physical fatigue, according to researchers.

“Our results point out that JIA is a controllable and treatable, but not curable, disease for a majority of the children,” coauthor Dr. Marite Rygg of St. Olav's Hospital, Trondheim, Norway, said in an interview.

Her colleague, Dr. Ellen Nordal, reported 7-year follow-up data on 427 children who were enrolled in the Nordic Juvenile Idiopathic Arthritis Cohort from 1997–2000. The cohort comprised patients from 12 centers in Norway, Finland, Sweden, and Denmark. At the congress, Dr. Nordal reported complete follow-up data on 427 of the children.

Most the patients (66%) were girls. Their median age at the onset of disease was 6 years. The most common arthritis subtype in the group was oligoarthritis; this was persistent in 126 and extended in 75. Other disease subtypes included polyarthritis (82); psoriatic arthritis (13); enthesitis-related arthritis (49); undifferentiated arthritis (64), and systemic arthritis (18). Uveitis developed in 89 children during the follow-up period.

At baseline, almost all of the children (97%) had taken a nonsteroidal anti-inflammatory drug. About half (48%) had taken methotrexate, while 74% had received intra-articular glucocorticoids and 32% received oral glucocorticoids. More than half (58%) had used a disease-modifying anti-rheumatic drug, including an anti-TNF (anti–tumor necrosis factor) drug. Only 3% were not taking any medications at baseline.

The mean follow-up period was 98 months. By then, 42% were in remission and off medication. However, more than half of the group (58%) were either not in remission (49%) or were in remission on medication (9%) said Dr. Nordal, a pediatric rheumatologist at the University Hospital of North Norway, Tromsø.

Rates of remission off medication varied by subtype, with the greatest rate occurring among those with systemic arthritis (83%). The lowest rates occurred in those with extended oligoarthritis (21%) and psoriatic arthritis (23%).

The highest rates of ongoing disease occurred in those who had rheumatoid factor–positive polyarthritis (67%) and extended oligoarthritis (63%). More than half of children with rheumatoid factor–negative polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis also failed to achieve remission.

Fatigue is another aspect of the disease that affects young people as they grow into their teens, according to registered nurse Deborah Hilderson of the Catholic University of Leuven, Belgium. She presented the results of a small cross-sectional study of 31 adolescents with JIA, which examined the impact of fatigue on their daily lives. The patients were compared with a group of healthy controls used in a 2003 study of excess fatigue in young adult survivors of childhood cancer (Eur. J. Cancer 2003;39:204–14).

The patients had a mean age of 16 years; all had been treated at the University Hospital Leuven (Belgium). Most (23) were female. Persistent or extended oligoarthritis was present in 11 patients; rheumatoid factor–negative polyarthritis in 9; systemic arthritis in 4; and enthesitis-related arthritis in 7.

They completed two quality of life measures. The Multidimensional Fatigue Inventory (MFI) scores fatigue on a 20-point scale in five domains: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. High scores indicate higher fatigue levels. The 100-point Quality of Life Linear Analog Scale rates 100 as the best quality of life imaginable, and 0 the worst.

About 13% of the patients reported a score of 15 or higher in the general fatigue domain of the MFI. There were no significant differences between the disease subtypes for any of the five fatigue domains. Compared with controls, patients reported significantly higher scores for physical fatigue and reduced activity. However, Ms. Hilderson noted, although the differences were statistically significant, the actual differences were “rather small.”

The median quality of life score was 74, but the range was wide (10–97). Higher quality of life scores were significantly associated with lower fatigue scores. There was a moderate association between quality of life and general and mental fatigue, Ms. Hilderson said.

“Fatigue does seem to be a problem for adolescents with JIA, and we, as health care providers, do need to pay attention to this complaint, particularly in patients with active arthritis,” Ms. Hilderson said.

Vitals

Source Elsevier Global Medical News

Circulating cytokines appear to influence fetal growth in pregnant women who have rheumatoid arthritis, results of a Dutch study suggest.

High levels of interleukin-10, IL-6, and TNF-alpha might all play a role – at different stages of pregnancy – to increase the risk of low birth weight among infants born to these mothers.

Dr. Radboud Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, and associates examined circulating cytokines in 134 pregnant patients with RA in their first trimester, 168 in their third trimester, and 33 healthy controls (J. Reprod. Immunol. [doi: 10.1016/j.jri.2010.08.010]).

Disease activity was based on the disease activity score for 28 joints (DAS28).

Among first trimester patients, 12 had detectable IL-10; all had a higher disease activity score than did those with no IL-10 (mean DAS28 4.4 vs. 3.6).

“In the first trimester, elevated IL-10 seems to protect against the negative influence of RA disease activity on birth weight, [while] IL-6 seems to amplify this negative influence,” they wrote. “In the third trimester, there is no influence, suggesting an early critical window.”

TNF-alpha, however, did exert an influence in the third trimester. This association was not present in the first trimester. This finding implies that “TNF blockers, which are more and more prescribed during pregnancy to treat [RA], should be used with caution,” they said.

The study was funded by the Dutch Arthritis Association. Dr. Dolhain did not disclose any pertinent conflicts.

Circulating cytokines appear to influence fetal growth in pregnant women who have rheumatoid arthritis, results of a Dutch study suggest.

High levels of interleukin-10, IL-6, and TNF-alpha might all play a role – at different stages of pregnancy – to increase the risk of low birth weight among infants born to these mothers.

Dr. Radboud Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, and associates examined circulating cytokines in 134 pregnant patients with RA in their first trimester, 168 in their third trimester, and 33 healthy controls (J. Reprod. Immunol. [doi: 10.1016/j.jri.2010.08.010]).

Disease activity was based on the disease activity score for 28 joints (DAS28).

Among first trimester patients, 12 had detectable IL-10; all had a higher disease activity score than did those with no IL-10 (mean DAS28 4.4 vs. 3.6).

“In the first trimester, elevated IL-10 seems to protect against the negative influence of RA disease activity on birth weight, [while] IL-6 seems to amplify this negative influence,” they wrote. “In the third trimester, there is no influence, suggesting an early critical window.”

TNF-alpha, however, did exert an influence in the third trimester. This association was not present in the first trimester. This finding implies that “TNF blockers, which are more and more prescribed during pregnancy to treat [RA], should be used with caution,” they said.

The study was funded by the Dutch Arthritis Association. Dr. Dolhain did not disclose any pertinent conflicts.

Circulating cytokines appear to influence fetal growth in pregnant women who have rheumatoid arthritis, results of a Dutch study suggest.

High levels of interleukin-10, IL-6, and TNF-alpha might all play a role – at different stages of pregnancy – to increase the risk of low birth weight among infants born to these mothers.

Dr. Radboud Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, and associates examined circulating cytokines in 134 pregnant patients with RA in their first trimester, 168 in their third trimester, and 33 healthy controls (J. Reprod. Immunol. [doi: 10.1016/j.jri.2010.08.010]).

Disease activity was based on the disease activity score for 28 joints (DAS28).

Among first trimester patients, 12 had detectable IL-10; all had a higher disease activity score than did those with no IL-10 (mean DAS28 4.4 vs. 3.6).

“In the first trimester, elevated IL-10 seems to protect against the negative influence of RA disease activity on birth weight, [while] IL-6 seems to amplify this negative influence,” they wrote. “In the third trimester, there is no influence, suggesting an early critical window.”

TNF-alpha, however, did exert an influence in the third trimester. This association was not present in the first trimester. This finding implies that “TNF blockers, which are more and more prescribed during pregnancy to treat [RA], should be used with caution,” they said.

The study was funded by the Dutch Arthritis Association. Dr. Dolhain did not disclose any pertinent conflicts.

An updated guideline for emergency cardiovascular care has changed the A-B-C mnemonic of cardiopulmonary resuscitation to C-A-B, emphasizing the need to start chest compressions as quickly as possible and worry about the airway second.

It's the biggest – and most important – change in the 2010 update of the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, said coauthor Dr. Michael Sayre, chairman of the American Heart Association's Emergency Cardiovascular Care (ECC) Committee.

“For more than 40 years, CPR training has emphasized the ABCs of CPR, which instructed people to open a victim's airway by tilting their head back, pinching the nose and breathing into the victim's mouth, and only then giving chest compressions,” Dr. Sayre said in a press statement. “This approach was causing significant delays in starting chest compressions, which are essential for keeping oxygen-rich blood circulating through the body. Changing the sequence from A-B-C to C-A-B for adults and children allows all rescuers to begin chest compressions right away.”

Any delay in chest compression, either by bystanders squeamish about mouth-to-mouth or clinicians searching for ventilation equipment, increases the risk of death, the statement noted. This change correlates with a British study published recently in Lancet, which found that nonprofessional rescuers are most effective when they use compression-only CPR (Lancet 2010 [doi:10.1016/S0140-6736(10)61454-7]).

The AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care were last updated in 2005, the authors said. Since then, a plethora of evidence has changed the clinical approach to emergency cardiovascular care. The committee, which included 356 resuscitation experts from 29 countries, produced 411 new evidence-based reviews, from which the updates were drawn.

The new recommendations also call for an increase in the rate of chest compressions, to at least 100/minute. “Rescuers should push deeper on the chest, compressing at least two inches in adults and children and 1.5 inches in infants,” the statement notes. “Between each compression, rescuers should avoid leaning on the chest to allow it to return to its starting position.”

The guidelines recommend the new C-A-B approach for adults, teens, and children who suddenly collapse and stop breathing, or display ineffective respiration during collapse. For neonates with no known cardiac etiology, however, the A-B-Cs remain in effect. Ventilation with room air is best for term babies in arrest; to avoid the negative impact of pure oxygen on newborns, the statement calls for a blend of room air and oxygen for infants who need supplemental oxygen. For these babies, the recommendation for a 3:1 chest compression–ventilation ratio remains in effect, because ventilation is critical to reversing neonatal asphyxia arrest.

Advanced Life Support

In addition to providing information for bystander rescue attempts, the guidelines suggest some changes in the way cardiac arrest and stroke patients are treated by emergency medical services, emergency physicians, and those involved with postincident care.

In keeping with the new C-A-B format, the document urges EMS personnel to minimize interruptions in chest compression to what is necessary for rescue ventilation. Even taking time for pulse checks is no longer advised, since pulse is not an effective indicator of cardiac status when blood pressure is low or absent.

Electrical therapy should be employed as soon as possible after CPR begins, but CPR should not cease while readying the defibrillator, the guidelines say. “Rescuers should minimize the interval between stopping compressions and delivering shocks, and should resume CPR immediately after shock delivery.”

The statement recommends an initial biphasic energy dose of 120-200 joules for atrial fibrillation and 50-100 joules for atrial flutter or other supraventricular tachycardias. If the initial shock fails, providers should increase the dose in a stepwise fashion.

For patients with symptomatic arrhythmias, the updates now recommend adenosine for diagnosing and treating stable undifferentiated wide-complex tachycardia when the rhythm is regular and the QRS wave is monomorphic. For symptomatic or unstable bradycardia, intravenous chronotropic agents can be an effective alternative to external pacing if adenosine is ineffective.

The guidelines include a major new class I recommendation for adult airway management: the use of quantitative waveform capnography for confirmation and monitoring of endotracheal tube placement. Additionally, they no longer endorse the routine use of cricoid pressure during airway management.

After the Cardiac Arrest

The recommendations don't stop when the patient regains spontaneous circulation. An entire section of the document is devoted to post–cardiac arrest care, pushing for an integrated, multidisciplinary approach. “Patients with suspected acute coronary syndrome should be triaged to a facility with reperfusion capabilities and a multidisciplinary team prepared to monitor patients for multi-organ dysfunction and initiate appropriate post–cardiac arrest therapy, including hypothermia.”

The guidelines deal with stroke separately, summarizing what should occur during out-of-hospital care through the first hours of therapy. One new recommendation is that acute stroke patients be triaged to a stroke center or dedicated stroke unit within 3 hours of presentation. The guidelines also expand the time window for administration of recombinant tissue plasminogen activator, and recommend it also be used in patients with acute ischemic stroke.

Many of the 33 writing members of the guidelines committee disclosed financial relationships, which are listed on the last page of the executive summary (Circulation 2010;122:S640-56).

An updated guideline for emergency cardiovascular care has changed the A-B-C mnemonic of cardiopulmonary resuscitation to C-A-B, emphasizing the need to start chest compressions as quickly as possible and worry about the airway second.

It's the biggest – and most important – change in the 2010 update of the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, said coauthor Dr. Michael Sayre, chairman of the American Heart Association's Emergency Cardiovascular Care (ECC) Committee.

“For more than 40 years, CPR training has emphasized the ABCs of CPR, which instructed people to open a victim's airway by tilting their head back, pinching the nose and breathing into the victim's mouth, and only then giving chest compressions,” Dr. Sayre said in a press statement. “This approach was causing significant delays in starting chest compressions, which are essential for keeping oxygen-rich blood circulating through the body. Changing the sequence from A-B-C to C-A-B for adults and children allows all rescuers to begin chest compressions right away.”

Any delay in chest compression, either by bystanders squeamish about mouth-to-mouth or clinicians searching for ventilation equipment, increases the risk of death, the statement noted. This change correlates with a British study published recently in Lancet, which found that nonprofessional rescuers are most effective when they use compression-only CPR (Lancet 2010 [doi:10.1016/S0140-6736(10)61454-7]).

The AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care were last updated in 2005, the authors said. Since then, a plethora of evidence has changed the clinical approach to emergency cardiovascular care. The committee, which included 356 resuscitation experts from 29 countries, produced 411 new evidence-based reviews, from which the updates were drawn.

The new recommendations also call for an increase in the rate of chest compressions, to at least 100/minute. “Rescuers should push deeper on the chest, compressing at least two inches in adults and children and 1.5 inches in infants,” the statement notes. “Between each compression, rescuers should avoid leaning on the chest to allow it to return to its starting position.”

The guidelines recommend the new C-A-B approach for adults, teens, and children who suddenly collapse and stop breathing, or display ineffective respiration during collapse. For neonates with no known cardiac etiology, however, the A-B-Cs remain in effect. Ventilation with room air is best for term babies in arrest; to avoid the negative impact of pure oxygen on newborns, the statement calls for a blend of room air and oxygen for infants who need supplemental oxygen. For these babies, the recommendation for a 3:1 chest compression–ventilation ratio remains in effect, because ventilation is critical to reversing neonatal asphyxia arrest.

Advanced Life Support

In addition to providing information for bystander rescue attempts, the guidelines suggest some changes in the way cardiac arrest and stroke patients are treated by emergency medical services, emergency physicians, and those involved with postincident care.

In keeping with the new C-A-B format, the document urges EMS personnel to minimize interruptions in chest compression to what is necessary for rescue ventilation. Even taking time for pulse checks is no longer advised, since pulse is not an effective indicator of cardiac status when blood pressure is low or absent.

Electrical therapy should be employed as soon as possible after CPR begins, but CPR should not cease while readying the defibrillator, the guidelines say. “Rescuers should minimize the interval between stopping compressions and delivering shocks, and should resume CPR immediately after shock delivery.”

The statement recommends an initial biphasic energy dose of 120-200 joules for atrial fibrillation and 50-100 joules for atrial flutter or other supraventricular tachycardias. If the initial shock fails, providers should increase the dose in a stepwise fashion.

For patients with symptomatic arrhythmias, the updates now recommend adenosine for diagnosing and treating stable undifferentiated wide-complex tachycardia when the rhythm is regular and the QRS wave is monomorphic. For symptomatic or unstable bradycardia, intravenous chronotropic agents can be an effective alternative to external pacing if adenosine is ineffective.

The guidelines include a major new class I recommendation for adult airway management: the use of quantitative waveform capnography for confirmation and monitoring of endotracheal tube placement. Additionally, they no longer endorse the routine use of cricoid pressure during airway management.

After the Cardiac Arrest

The recommendations don't stop when the patient regains spontaneous circulation. An entire section of the document is devoted to post–cardiac arrest care, pushing for an integrated, multidisciplinary approach. “Patients with suspected acute coronary syndrome should be triaged to a facility with reperfusion capabilities and a multidisciplinary team prepared to monitor patients for multi-organ dysfunction and initiate appropriate post–cardiac arrest therapy, including hypothermia.”

The guidelines deal with stroke separately, summarizing what should occur during out-of-hospital care through the first hours of therapy. One new recommendation is that acute stroke patients be triaged to a stroke center or dedicated stroke unit within 3 hours of presentation. The guidelines also expand the time window for administration of recombinant tissue plasminogen activator, and recommend it also be used in patients with acute ischemic stroke.

Many of the 33 writing members of the guidelines committee disclosed financial relationships, which are listed on the last page of the executive summary (Circulation 2010;122:S640-56).

An updated guideline for emergency cardiovascular care has changed the A-B-C mnemonic of cardiopulmonary resuscitation to C-A-B, emphasizing the need to start chest compressions as quickly as possible and worry about the airway second.

It's the biggest – and most important – change in the 2010 update of the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, said coauthor Dr. Michael Sayre, chairman of the American Heart Association's Emergency Cardiovascular Care (ECC) Committee.

“For more than 40 years, CPR training has emphasized the ABCs of CPR, which instructed people to open a victim's airway by tilting their head back, pinching the nose and breathing into the victim's mouth, and only then giving chest compressions,” Dr. Sayre said in a press statement. “This approach was causing significant delays in starting chest compressions, which are essential for keeping oxygen-rich blood circulating through the body. Changing the sequence from A-B-C to C-A-B for adults and children allows all rescuers to begin chest compressions right away.”

Any delay in chest compression, either by bystanders squeamish about mouth-to-mouth or clinicians searching for ventilation equipment, increases the risk of death, the statement noted. This change correlates with a British study published recently in Lancet, which found that nonprofessional rescuers are most effective when they use compression-only CPR (Lancet 2010 [doi:10.1016/S0140-6736(10)61454-7]).

The AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care were last updated in 2005, the authors said. Since then, a plethora of evidence has changed the clinical approach to emergency cardiovascular care. The committee, which included 356 resuscitation experts from 29 countries, produced 411 new evidence-based reviews, from which the updates were drawn.

The new recommendations also call for an increase in the rate of chest compressions, to at least 100/minute. “Rescuers should push deeper on the chest, compressing at least two inches in adults and children and 1.5 inches in infants,” the statement notes. “Between each compression, rescuers should avoid leaning on the chest to allow it to return to its starting position.”

The guidelines recommend the new C-A-B approach for adults, teens, and children who suddenly collapse and stop breathing, or display ineffective respiration during collapse. For neonates with no known cardiac etiology, however, the A-B-Cs remain in effect. Ventilation with room air is best for term babies in arrest; to avoid the negative impact of pure oxygen on newborns, the statement calls for a blend of room air and oxygen for infants who need supplemental oxygen. For these babies, the recommendation for a 3:1 chest compression–ventilation ratio remains in effect, because ventilation is critical to reversing neonatal asphyxia arrest.

Advanced Life Support

In addition to providing information for bystander rescue attempts, the guidelines suggest some changes in the way cardiac arrest and stroke patients are treated by emergency medical services, emergency physicians, and those involved with postincident care.

In keeping with the new C-A-B format, the document urges EMS personnel to minimize interruptions in chest compression to what is necessary for rescue ventilation. Even taking time for pulse checks is no longer advised, since pulse is not an effective indicator of cardiac status when blood pressure is low or absent.

Electrical therapy should be employed as soon as possible after CPR begins, but CPR should not cease while readying the defibrillator, the guidelines say. “Rescuers should minimize the interval between stopping compressions and delivering shocks, and should resume CPR immediately after shock delivery.”

The statement recommends an initial biphasic energy dose of 120-200 joules for atrial fibrillation and 50-100 joules for atrial flutter or other supraventricular tachycardias. If the initial shock fails, providers should increase the dose in a stepwise fashion.

For patients with symptomatic arrhythmias, the updates now recommend adenosine for diagnosing and treating stable undifferentiated wide-complex tachycardia when the rhythm is regular and the QRS wave is monomorphic. For symptomatic or unstable bradycardia, intravenous chronotropic agents can be an effective alternative to external pacing if adenosine is ineffective.

The guidelines include a major new class I recommendation for adult airway management: the use of quantitative waveform capnography for confirmation and monitoring of endotracheal tube placement. Additionally, they no longer endorse the routine use of cricoid pressure during airway management.

After the Cardiac Arrest

The recommendations don't stop when the patient regains spontaneous circulation. An entire section of the document is devoted to post–cardiac arrest care, pushing for an integrated, multidisciplinary approach. “Patients with suspected acute coronary syndrome should be triaged to a facility with reperfusion capabilities and a multidisciplinary team prepared to monitor patients for multi-organ dysfunction and initiate appropriate post–cardiac arrest therapy, including hypothermia.”

The guidelines deal with stroke separately, summarizing what should occur during out-of-hospital care through the first hours of therapy. One new recommendation is that acute stroke patients be triaged to a stroke center or dedicated stroke unit within 3 hours of presentation. The guidelines also expand the time window for administration of recombinant tissue plasminogen activator, and recommend it also be used in patients with acute ischemic stroke.

Many of the 33 writing members of the guidelines committee disclosed financial relationships, which are listed on the last page of the executive summary (Circulation 2010;122:S640-56).

HONOLULU – Reearchers are making small steps toward untangling the mysteries of tau – the protein that twists around neurons and destroys cognitive ability in Alzheimer's disease.

The beta amyloid protein, which forms the sticky brain plaques characteristic of the disease, is now considered the “upstream” lesion of Alzheimer's – a prodromal manifestation that appears before the onset of symptoms. The neurofibrillary tangles of phosphorylated tau that appear in both the neuronal cell bodies and dendritic spines occur later and directly correlate with cognitive decline.

In several studies presented at the meeting, which was sponsored by the Alzheimer's Association, scientists gave tantalizing clues to the connection between beta amyloid (Abeta) and tau, and the possible effects of untangling tau's destructive web with immunotherapy.

“Importantly, these studies teach us more not only about tau-targeted therapies, but also about the progression of Alzheimer's disease,” William Thies, Ph.D., said at a press briefing on the studies. “It may be that amyloid changes in the brain happen early in the disease and the tau-related changes happen 'downstream,' where they have a more direct effect on cognitive function,”Hsaid Dr. Thies, chief medical and scientific officer of the Alzheimer's Association.

Dr. Kaj Blennow of the University of Gothenburg (Sweden), discussed a pooled analysis of data collected from two randomized, placebo-controlled studies of bapineuzumab (Janssen and Pfizer Inc.), an antibody to Abeta plaques. The drug iscin phase III trials. It induces anti-Abeta antibodies, which have been shown to reduce Abeta plaques.

The subgroup analysis consisted of 46 Alzheimer's patients who were enrolled in either Study 201 (United States) or Study 202 (United Kingdom and Finland). Of these patients, 27 received bapineuzumab and 19 received placebo.

In Study 201, the active group showed a nonsignificant decrease in phosphorylated tau – the kind associated with neuronal death – in cerebrospinal fluid, compared with the control group. In study 202, there were no tau-related treatment effects. When the data were combined, however, Dr. Blennow and his colleagues found a significantly greater decrease in phosphorylated tau in bapineuzumab-treated patients, compared with placebo-treated patients (−9.5 picograms/mL vs. −0.5 picograms/mL). In the pooled data, Dr. Blennow also found a trend toward a decrease in total CSF tau in the active group, compared with the control group.

“These observations suggest that immunotherapy targeting amyloid may also alter neurodegenerative processes that occur later in the disease process and that are more directly associated with loss of function,” Dr. Blennow said at the briefing.

Delphine Boche, Ph.D., of the University of Southampton (England), studied the tau effects of another Abeta immunotherapy agent called AN1792, which was pulled from development in 2002 after 6% of the patients who received it developed serious brain inflammation and subsequent brain atrophy.

A number of the patients in the AN1792 trial have since died. Researchers continue to examine their brains to discover other effects of the vaccine, which was designed to reduce brain plaques. Dr. Boche compared samples from the brains of 10 immunized Alzheimer's patients with samples from the brains of 28 nonimmunized patients.

Dr. Boche and her team quantified Abeta-42 – the plaque-forming length of the Abeta peptide – and phosphorylated tau in six brain areas affected by Alzheimer's pathology: the superior and middle temporal gyrus, medial frontal gyrus, inferior parietal lobule, entorhinal cortex, and subiculum and CA1 regions of the hippocampus.

The researchers found that immunized brains had a significantly lower percentage of cerebral cortex covered by Abeta plaque than did the nonimmunized brains (1.4% vs. 5.25%). There was also a significantly lower load of phosphorylated tau in immunized patients in the same regions (0.72% vs. 1.08%).

Dr. Boche also examined neurons to determine whether the tau changes were intra- or extracellular. “The load was significantly lower in the fine dendritic branches compared with the neuron body,” she said. “When the Abeta was removed, the dystrophic neurites also disappeared. But there was no significant difference in the level of tau within the nerve body.”

Unfortunately, the physiologic changes did not translate into any clinical benefit. “All the vaccinated patients [who are still alive] are still deteriorating despite the treatment,” she said.

The final study examined the effect of an active tau immunotherapy on mice engineered to develop neurofibrillary tau tangles. Allal Boutajangout, Ph.D., of New York University, New York, and his colleagues used a monoclonal antibody called PHF1, which recognizes and attacks phosphorylated tau.

Mice that were 2-3 months old received 13 peritoneal injections of the antibody or 13 injections of mouse immunoglobulin G. At 5-6 months old, their behavior was assessed and then they were sacrificed for brain pathology.

The treated mice performed significantly better than the controls on a task that examined balance, general motor coordination, and functional integration. Their brains also showed 58% less tau pathology in the dentate gyrus of the hippocampus—an area important in memory.

Dr. Blennow's study was supported by Janssen Alzheimer Immunotherapy. Dr. Blennow had no relevant financial disclosures, but several of his coauthors are employees of Janssen, Pfizer, or Elan Pharmaceuticals, and own stock in the companies. Dr. Boche's study was sponsored by the Alzheimer's Research Trust; she and her coauthors reported having no financial disclosures. Dr. Boutajangout's study was sponsored by the Alzheimer's Association and Applied Neurosciences. Neither he nor his coauthors reported having any financial conflicts.

HONOLULU – Reearchers are making small steps toward untangling the mysteries of tau – the protein that twists around neurons and destroys cognitive ability in Alzheimer's disease.

The beta amyloid protein, which forms the sticky brain plaques characteristic of the disease, is now considered the “upstream” lesion of Alzheimer's – a prodromal manifestation that appears before the onset of symptoms. The neurofibrillary tangles of phosphorylated tau that appear in both the neuronal cell bodies and dendritic spines occur later and directly correlate with cognitive decline.

In several studies presented at the meeting, which was sponsored by the Alzheimer's Association, scientists gave tantalizing clues to the connection between beta amyloid (Abeta) and tau, and the possible effects of untangling tau's destructive web with immunotherapy.

“Importantly, these studies teach us more not only about tau-targeted therapies, but also about the progression of Alzheimer's disease,” William Thies, Ph.D., said at a press briefing on the studies. “It may be that amyloid changes in the brain happen early in the disease and the tau-related changes happen 'downstream,' where they have a more direct effect on cognitive function,”Hsaid Dr. Thies, chief medical and scientific officer of the Alzheimer's Association.

Dr. Kaj Blennow of the University of Gothenburg (Sweden), discussed a pooled analysis of data collected from two randomized, placebo-controlled studies of bapineuzumab (Janssen and Pfizer Inc.), an antibody to Abeta plaques. The drug iscin phase III trials. It induces anti-Abeta antibodies, which have been shown to reduce Abeta plaques.

The subgroup analysis consisted of 46 Alzheimer's patients who were enrolled in either Study 201 (United States) or Study 202 (United Kingdom and Finland). Of these patients, 27 received bapineuzumab and 19 received placebo.

In Study 201, the active group showed a nonsignificant decrease in phosphorylated tau – the kind associated with neuronal death – in cerebrospinal fluid, compared with the control group. In study 202, there were no tau-related treatment effects. When the data were combined, however, Dr. Blennow and his colleagues found a significantly greater decrease in phosphorylated tau in bapineuzumab-treated patients, compared with placebo-treated patients (−9.5 picograms/mL vs. −0.5 picograms/mL). In the pooled data, Dr. Blennow also found a trend toward a decrease in total CSF tau in the active group, compared with the control group.

“These observations suggest that immunotherapy targeting amyloid may also alter neurodegenerative processes that occur later in the disease process and that are more directly associated with loss of function,” Dr. Blennow said at the briefing.

Delphine Boche, Ph.D., of the University of Southampton (England), studied the tau effects of another Abeta immunotherapy agent called AN1792, which was pulled from development in 2002 after 6% of the patients who received it developed serious brain inflammation and subsequent brain atrophy.

A number of the patients in the AN1792 trial have since died. Researchers continue to examine their brains to discover other effects of the vaccine, which was designed to reduce brain plaques. Dr. Boche compared samples from the brains of 10 immunized Alzheimer's patients with samples from the brains of 28 nonimmunized patients.

Dr. Boche and her team quantified Abeta-42 – the plaque-forming length of the Abeta peptide – and phosphorylated tau in six brain areas affected by Alzheimer's pathology: the superior and middle temporal gyrus, medial frontal gyrus, inferior parietal lobule, entorhinal cortex, and subiculum and CA1 regions of the hippocampus.

The researchers found that immunized brains had a significantly lower percentage of cerebral cortex covered by Abeta plaque than did the nonimmunized brains (1.4% vs. 5.25%). There was also a significantly lower load of phosphorylated tau in immunized patients in the same regions (0.72% vs. 1.08%).

Dr. Boche also examined neurons to determine whether the tau changes were intra- or extracellular. “The load was significantly lower in the fine dendritic branches compared with the neuron body,” she said. “When the Abeta was removed, the dystrophic neurites also disappeared. But there was no significant difference in the level of tau within the nerve body.”

Unfortunately, the physiologic changes did not translate into any clinical benefit. “All the vaccinated patients [who are still alive] are still deteriorating despite the treatment,” she said.

The final study examined the effect of an active tau immunotherapy on mice engineered to develop neurofibrillary tau tangles. Allal Boutajangout, Ph.D., of New York University, New York, and his colleagues used a monoclonal antibody called PHF1, which recognizes and attacks phosphorylated tau.

Mice that were 2-3 months old received 13 peritoneal injections of the antibody or 13 injections of mouse immunoglobulin G. At 5-6 months old, their behavior was assessed and then they were sacrificed for brain pathology.

The treated mice performed significantly better than the controls on a task that examined balance, general motor coordination, and functional integration. Their brains also showed 58% less tau pathology in the dentate gyrus of the hippocampus—an area important in memory.

Dr. Blennow's study was supported by Janssen Alzheimer Immunotherapy. Dr. Blennow had no relevant financial disclosures, but several of his coauthors are employees of Janssen, Pfizer, or Elan Pharmaceuticals, and own stock in the companies. Dr. Boche's study was sponsored by the Alzheimer's Research Trust; she and her coauthors reported having no financial disclosures. Dr. Boutajangout's study was sponsored by the Alzheimer's Association and Applied Neurosciences. Neither he nor his coauthors reported having any financial conflicts.

HONOLULU – Reearchers are making small steps toward untangling the mysteries of tau – the protein that twists around neurons and destroys cognitive ability in Alzheimer's disease.

The beta amyloid protein, which forms the sticky brain plaques characteristic of the disease, is now considered the “upstream” lesion of Alzheimer's – a prodromal manifestation that appears before the onset of symptoms. The neurofibrillary tangles of phosphorylated tau that appear in both the neuronal cell bodies and dendritic spines occur later and directly correlate with cognitive decline.

In several studies presented at the meeting, which was sponsored by the Alzheimer's Association, scientists gave tantalizing clues to the connection between beta amyloid (Abeta) and tau, and the possible effects of untangling tau's destructive web with immunotherapy.

“Importantly, these studies teach us more not only about tau-targeted therapies, but also about the progression of Alzheimer's disease,” William Thies, Ph.D., said at a press briefing on the studies. “It may be that amyloid changes in the brain happen early in the disease and the tau-related changes happen 'downstream,' where they have a more direct effect on cognitive function,”Hsaid Dr. Thies, chief medical and scientific officer of the Alzheimer's Association.

Dr. Kaj Blennow of the University of Gothenburg (Sweden), discussed a pooled analysis of data collected from two randomized, placebo-controlled studies of bapineuzumab (Janssen and Pfizer Inc.), an antibody to Abeta plaques. The drug iscin phase III trials. It induces anti-Abeta antibodies, which have been shown to reduce Abeta plaques.

The subgroup analysis consisted of 46 Alzheimer's patients who were enrolled in either Study 201 (United States) or Study 202 (United Kingdom and Finland). Of these patients, 27 received bapineuzumab and 19 received placebo.

In Study 201, the active group showed a nonsignificant decrease in phosphorylated tau – the kind associated with neuronal death – in cerebrospinal fluid, compared with the control group. In study 202, there were no tau-related treatment effects. When the data were combined, however, Dr. Blennow and his colleagues found a significantly greater decrease in phosphorylated tau in bapineuzumab-treated patients, compared with placebo-treated patients (−9.5 picograms/mL vs. −0.5 picograms/mL). In the pooled data, Dr. Blennow also found a trend toward a decrease in total CSF tau in the active group, compared with the control group.

“These observations suggest that immunotherapy targeting amyloid may also alter neurodegenerative processes that occur later in the disease process and that are more directly associated with loss of function,” Dr. Blennow said at the briefing.

Delphine Boche, Ph.D., of the University of Southampton (England), studied the tau effects of another Abeta immunotherapy agent called AN1792, which was pulled from development in 2002 after 6% of the patients who received it developed serious brain inflammation and subsequent brain atrophy.

A number of the patients in the AN1792 trial have since died. Researchers continue to examine their brains to discover other effects of the vaccine, which was designed to reduce brain plaques. Dr. Boche compared samples from the brains of 10 immunized Alzheimer's patients with samples from the brains of 28 nonimmunized patients.

Dr. Boche and her team quantified Abeta-42 – the plaque-forming length of the Abeta peptide – and phosphorylated tau in six brain areas affected by Alzheimer's pathology: the superior and middle temporal gyrus, medial frontal gyrus, inferior parietal lobule, entorhinal cortex, and subiculum and CA1 regions of the hippocampus.

The researchers found that immunized brains had a significantly lower percentage of cerebral cortex covered by Abeta plaque than did the nonimmunized brains (1.4% vs. 5.25%). There was also a significantly lower load of phosphorylated tau in immunized patients in the same regions (0.72% vs. 1.08%).

Dr. Boche also examined neurons to determine whether the tau changes were intra- or extracellular. “The load was significantly lower in the fine dendritic branches compared with the neuron body,” she said. “When the Abeta was removed, the dystrophic neurites also disappeared. But there was no significant difference in the level of tau within the nerve body.”

Unfortunately, the physiologic changes did not translate into any clinical benefit. “All the vaccinated patients [who are still alive] are still deteriorating despite the treatment,” she said.

The final study examined the effect of an active tau immunotherapy on mice engineered to develop neurofibrillary tau tangles. Allal Boutajangout, Ph.D., of New York University, New York, and his colleagues used a monoclonal antibody called PHF1, which recognizes and attacks phosphorylated tau.

Mice that were 2-3 months old received 13 peritoneal injections of the antibody or 13 injections of mouse immunoglobulin G. At 5-6 months old, their behavior was assessed and then they were sacrificed for brain pathology.

The treated mice performed significantly better than the controls on a task that examined balance, general motor coordination, and functional integration. Their brains also showed 58% less tau pathology in the dentate gyrus of the hippocampus—an area important in memory.

Dr. Blennow's study was supported by Janssen Alzheimer Immunotherapy. Dr. Blennow had no relevant financial disclosures, but several of his coauthors are employees of Janssen, Pfizer, or Elan Pharmaceuticals, and own stock in the companies. Dr. Boche's study was sponsored by the Alzheimer's Research Trust; she and her coauthors reported having no financial disclosures. Dr. Boutajangout's study was sponsored by the Alzheimer's Association and Applied Neurosciences. Neither he nor his coauthors reported having any financial conflicts.

CHICAGO – Patients with severe acne are missing out on the skin-clearing benefits of oral contraceptives and need to know that OCs can be prescribed for acne without a pelvic examination by a gynecologist, according to Dr. Bethanee Schlosser.

“When talking to teens and their parents, it's important to explain that a pelvic exam is not necessary before giving these medications to young women,” she said.

It appears that patients aren't privy to this information, and are reluctant to ask for oral contraceptives as acne medication. “That may be the biggest hurdle keeping these patients from getting adequate treatment for their acne,” she said.

In 2004, the World Health Organization released guidelines stating that pelvic exams and Pap smears are no longer required before administering combination oral contraceptives.

Dr. Schlosser noted, however, that she does ask all of her female patients when they had their last full gynecologic exam, Pap smear included, and encourages them to stay current.

Three combination oral contraceptives are approved for the treatment of acne in women in the United States: ethinyl estradiol and norgestimate (Ortho Tri-Cyclen), ethinyl estradiol and norethindrone (Estrostep), and ethinyl estradiol and drospirenone (Yaz).

Drospironone, an analogue of spironolactone, reduces sebum production and increases sex hormone–binding globulin, thus reducing circulating androgens, Dr. Schlosser said.

“Some women will come to me, though, and say that their ob.gyn. has told them they can't take any pill containing drospirenone or spironolactone,” because of its possible effect on potassium levels, especially in combination with other drugs that increase serum potassium (ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatories).

Dr. Schlosser pointed to a 2009 study of 27 women with either severe papular or nodulocystic acne who were treated with a combined oral contraceptive containing 30 mg ethinyl estradiol, 3 mg drospirenone, and 100 mg spironolactone. None of the patients had a significant elevation in serum potassium level; there were no reports of adverse events serious enough to require discontinuation of treatment. At follow-up, 85% of subjects were entirely clear of acne lesions or had excellent improvement, 7% were mildly improved, and 7% were not improved (J. Am. Acad. Derm. 2008;58:60-2).

A 2008 study looked only at the risk of hyperkalemia among 22,429 women who used the drospirenone-containing contraceptive, compared with 44,858 who used other oral contraceptives. (Contraception 2008;78:377-83). There was no significant between-group difference in the incidence of hyperkalemia.

This type of treatment is not an overnight acne cure, Dr. Schlosser stressed. “I tell women you have to allow at least three cycles of use before you start to judge efficacy. Patients can continue to get more benefit from 3-6 months of use, too.”

A 2007 Cochrane review of the three Food and Drug Administration–approved acne-fighting oral contraceptives found no significant differences in effectiveness, she said.

Elevated androgens are a large contributor to acne in women, and both the estradiol and progestins in combination oral contraceptives work to decrease them, said Dr. Schlosser, director of the women's skin health program at Northwestern University, Chicago. Androgen testing may be appropriate for some women.

“If a woman complains of sudden onset of acne, or acne that is severe or recalcitrant to traditional therapy, I would say testing is a good idea. You might also consider it for women with androgenic features—hirsutism, deep voice, muscular habitus, or androgenic alopecia,” she said.

Because these features can also be symptoms of polycystic ovary syndrome, Dr. Schlosser also suggested checking for acanthosis nigricans, central obesity, irregular menses, and infertility.

Androgen testing is most informative when performed at the onset of menses. “This is because androgen secretion follows the same pattern as estradiol, which peaks in midcycle and falls to a nadir at the beginning of menstruation,” Dr. Schlosser said.

“I print out a lab request, and tell the patient to have her blood drawn on the first day of her period.” Morning testing is better, if possible, because of the hormone's diurnal secretion.

Total testosterone is the most sensitive test for androgen levels in women with acne. However, “it's important to note that the levels associated with acne can be elevated compared to controls, but still within the normal reference ranges,” she said. Total testosterone level can also be falsely elevated in obese women, “because insulin reduces the liver's secretion of sex hormone–binding globulin,” she said.

There are some contraindications to the use of oral contraceptives for the treatment of acne, Dr. Schlosser noted. Hypercoagulability, a history of venous thromboembolism (VTE), stroke, coronary artery disease, any gynecologic cancer, uncontrolled hypertension, abnormal liver function tests, pregnancy, or abnormal vaginal bleeding should be considered before prescribing.

Oral contraceptives do increase the risk of venous thromboembolism, although that risk is highly dependent on other factors as well, including advancing age and tobacco use. Dr. Schlosser said a concrete, direct link between oral contraceptives and VTE risk has yet to be found, but he hopes an ongoing case-control study of more than 50,000 oral contraceptive users (including up to 5 years of follow-up data) will provide answers.

Finally, Dr. Schlosser added, the single greatest risk of VTE among women is pregnancy and the postpartum period. “So I would say if you're treating acne in a woman of childbearing age with an oral contraceptive, you are also protecting her from the biggest risk factor she has for thromboembolic events.”

Dr. Schlosser said she had no relevant financial disclosures.

CHICAGO – Patients with severe acne are missing out on the skin-clearing benefits of oral contraceptives and need to know that OCs can be prescribed for acne without a pelvic examination by a gynecologist, according to Dr. Bethanee Schlosser.

“When talking to teens and their parents, it's important to explain that a pelvic exam is not necessary before giving these medications to young women,” she said.

It appears that patients aren't privy to this information, and are reluctant to ask for oral contraceptives as acne medication. “That may be the biggest hurdle keeping these patients from getting adequate treatment for their acne,” she said.

In 2004, the World Health Organization released guidelines stating that pelvic exams and Pap smears are no longer required before administering combination oral contraceptives.

Dr. Schlosser noted, however, that she does ask all of her female patients when they had their last full gynecologic exam, Pap smear included, and encourages them to stay current.

Three combination oral contraceptives are approved for the treatment of acne in women in the United States: ethinyl estradiol and norgestimate (Ortho Tri-Cyclen), ethinyl estradiol and norethindrone (Estrostep), and ethinyl estradiol and drospirenone (Yaz).

Drospironone, an analogue of spironolactone, reduces sebum production and increases sex hormone–binding globulin, thus reducing circulating androgens, Dr. Schlosser said.

“Some women will come to me, though, and say that their ob.gyn. has told them they can't take any pill containing drospirenone or spironolactone,” because of its possible effect on potassium levels, especially in combination with other drugs that increase serum potassium (ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatories).

Dr. Schlosser pointed to a 2009 study of 27 women with either severe papular or nodulocystic acne who were treated with a combined oral contraceptive containing 30 mg ethinyl estradiol, 3 mg drospirenone, and 100 mg spironolactone. None of the patients had a significant elevation in serum potassium level; there were no reports of adverse events serious enough to require discontinuation of treatment. At follow-up, 85% of subjects were entirely clear of acne lesions or had excellent improvement, 7% were mildly improved, and 7% were not improved (J. Am. Acad. Derm. 2008;58:60-2).

A 2008 study looked only at the risk of hyperkalemia among 22,429 women who used the drospirenone-containing contraceptive, compared with 44,858 who used other oral contraceptives. (Contraception 2008;78:377-83). There was no significant between-group difference in the incidence of hyperkalemia.

This type of treatment is not an overnight acne cure, Dr. Schlosser stressed. “I tell women you have to allow at least three cycles of use before you start to judge efficacy. Patients can continue to get more benefit from 3-6 months of use, too.”

A 2007 Cochrane review of the three Food and Drug Administration–approved acne-fighting oral contraceptives found no significant differences in effectiveness, she said.

Elevated androgens are a large contributor to acne in women, and both the estradiol and progestins in combination oral contraceptives work to decrease them, said Dr. Schlosser, director of the women's skin health program at Northwestern University, Chicago. Androgen testing may be appropriate for some women.

“If a woman complains of sudden onset of acne, or acne that is severe or recalcitrant to traditional therapy, I would say testing is a good idea. You might also consider it for women with androgenic features—hirsutism, deep voice, muscular habitus, or androgenic alopecia,” she said.

Because these features can also be symptoms of polycystic ovary syndrome, Dr. Schlosser also suggested checking for acanthosis nigricans, central obesity, irregular menses, and infertility.

Androgen testing is most informative when performed at the onset of menses. “This is because androgen secretion follows the same pattern as estradiol, which peaks in midcycle and falls to a nadir at the beginning of menstruation,” Dr. Schlosser said.

“I print out a lab request, and tell the patient to have her blood drawn on the first day of her period.” Morning testing is better, if possible, because of the hormone's diurnal secretion.

Total testosterone is the most sensitive test for androgen levels in women with acne. However, “it's important to note that the levels associated with acne can be elevated compared to controls, but still within the normal reference ranges,” she said. Total testosterone level can also be falsely elevated in obese women, “because insulin reduces the liver's secretion of sex hormone–binding globulin,” she said.

There are some contraindications to the use of oral contraceptives for the treatment of acne, Dr. Schlosser noted. Hypercoagulability, a history of venous thromboembolism (VTE), stroke, coronary artery disease, any gynecologic cancer, uncontrolled hypertension, abnormal liver function tests, pregnancy, or abnormal vaginal bleeding should be considered before prescribing.

Oral contraceptives do increase the risk of venous thromboembolism, although that risk is highly dependent on other factors as well, including advancing age and tobacco use. Dr. Schlosser said a concrete, direct link between oral contraceptives and VTE risk has yet to be found, but he hopes an ongoing case-control study of more than 50,000 oral contraceptive users (including up to 5 years of follow-up data) will provide answers.

Finally, Dr. Schlosser added, the single greatest risk of VTE among women is pregnancy and the postpartum period. “So I would say if you're treating acne in a woman of childbearing age with an oral contraceptive, you are also protecting her from the biggest risk factor she has for thromboembolic events.”

Dr. Schlosser said she had no relevant financial disclosures.

CHICAGO – Patients with severe acne are missing out on the skin-clearing benefits of oral contraceptives and need to know that OCs can be prescribed for acne without a pelvic examination by a gynecologist, according to Dr. Bethanee Schlosser.

“When talking to teens and their parents, it's important to explain that a pelvic exam is not necessary before giving these medications to young women,” she said.

It appears that patients aren't privy to this information, and are reluctant to ask for oral contraceptives as acne medication. “That may be the biggest hurdle keeping these patients from getting adequate treatment for their acne,” she said.

In 2004, the World Health Organization released guidelines stating that pelvic exams and Pap smears are no longer required before administering combination oral contraceptives.

Dr. Schlosser noted, however, that she does ask all of her female patients when they had their last full gynecologic exam, Pap smear included, and encourages them to stay current.

Three combination oral contraceptives are approved for the treatment of acne in women in the United States: ethinyl estradiol and norgestimate (Ortho Tri-Cyclen), ethinyl estradiol and norethindrone (Estrostep), and ethinyl estradiol and drospirenone (Yaz).

Drospironone, an analogue of spironolactone, reduces sebum production and increases sex hormone–binding globulin, thus reducing circulating androgens, Dr. Schlosser said.

“Some women will come to me, though, and say that their ob.gyn. has told them they can't take any pill containing drospirenone or spironolactone,” because of its possible effect on potassium levels, especially in combination with other drugs that increase serum potassium (ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatories).

Dr. Schlosser pointed to a 2009 study of 27 women with either severe papular or nodulocystic acne who were treated with a combined oral contraceptive containing 30 mg ethinyl estradiol, 3 mg drospirenone, and 100 mg spironolactone. None of the patients had a significant elevation in serum potassium level; there were no reports of adverse events serious enough to require discontinuation of treatment. At follow-up, 85% of subjects were entirely clear of acne lesions or had excellent improvement, 7% were mildly improved, and 7% were not improved (J. Am. Acad. Derm. 2008;58:60-2).

A 2008 study looked only at the risk of hyperkalemia among 22,429 women who used the drospirenone-containing contraceptive, compared with 44,858 who used other oral contraceptives. (Contraception 2008;78:377-83). There was no significant between-group difference in the incidence of hyperkalemia.

This type of treatment is not an overnight acne cure, Dr. Schlosser stressed. “I tell women you have to allow at least three cycles of use before you start to judge efficacy. Patients can continue to get more benefit from 3-6 months of use, too.”

A 2007 Cochrane review of the three Food and Drug Administration–approved acne-fighting oral contraceptives found no significant differences in effectiveness, she said.

Elevated androgens are a large contributor to acne in women, and both the estradiol and progestins in combination oral contraceptives work to decrease them, said Dr. Schlosser, director of the women's skin health program at Northwestern University, Chicago. Androgen testing may be appropriate for some women.

“If a woman complains of sudden onset of acne, or acne that is severe or recalcitrant to traditional therapy, I would say testing is a good idea. You might also consider it for women with androgenic features—hirsutism, deep voice, muscular habitus, or androgenic alopecia,” she said.

Because these features can also be symptoms of polycystic ovary syndrome, Dr. Schlosser also suggested checking for acanthosis nigricans, central obesity, irregular menses, and infertility.

Androgen testing is most informative when performed at the onset of menses. “This is because androgen secretion follows the same pattern as estradiol, which peaks in midcycle and falls to a nadir at the beginning of menstruation,” Dr. Schlosser said.

“I print out a lab request, and tell the patient to have her blood drawn on the first day of her period.” Morning testing is better, if possible, because of the hormone's diurnal secretion.

Total testosterone is the most sensitive test for androgen levels in women with acne. However, “it's important to note that the levels associated with acne can be elevated compared to controls, but still within the normal reference ranges,” she said. Total testosterone level can also be falsely elevated in obese women, “because insulin reduces the liver's secretion of sex hormone–binding globulin,” she said.

There are some contraindications to the use of oral contraceptives for the treatment of acne, Dr. Schlosser noted. Hypercoagulability, a history of venous thromboembolism (VTE), stroke, coronary artery disease, any gynecologic cancer, uncontrolled hypertension, abnormal liver function tests, pregnancy, or abnormal vaginal bleeding should be considered before prescribing.

Oral contraceptives do increase the risk of venous thromboembolism, although that risk is highly dependent on other factors as well, including advancing age and tobacco use. Dr. Schlosser said a concrete, direct link between oral contraceptives and VTE risk has yet to be found, but he hopes an ongoing case-control study of more than 50,000 oral contraceptive users (including up to 5 years of follow-up data) will provide answers.

Finally, Dr. Schlosser added, the single greatest risk of VTE among women is pregnancy and the postpartum period. “So I would say if you're treating acne in a woman of childbearing age with an oral contraceptive, you are also protecting her from the biggest risk factor she has for thromboembolic events.”

Dr. Schlosser said she had no relevant financial disclosures.

ORLANDO – Shared medical appointments offer an effective way to manage patients with diabetes, providing them with personal and professional interactions that improve clinical outcomes and self-care as well as fostering personal growth.

The programs, which usually include seeing 5-15 patients during a 1.5- to 2-hour period, allow providers to maximize their teaching and clinical care time and can actually be a lucrative way of managing this population, Mary Ann Hodorowicz said.

This newer method for managing office patients with chronic conditions allows providers to maximize their clinical care and face-to-face time with their patients. Diabetes self-management training or medical nutrition therapy is also offered during the visit by a diabetes educator or a registered dietician; patients interact with one another to help further their learning.

Shared medical appointments are not only cost effective but also much more profitable in terms of payer reimbursement, compared with individual visits, said Ms. Hodorowicz, a certified diabetes educator and registered dietician who specializes in reimbursement for diabetes services.

“I'm the queen of acronyms, and 'MORE' is a great one to describe the shared medical appointment for diabetes care. You and your patients get MORE results: Maximization of Outcomes, Revenue, and Empowerment of patients.”

Because Medicare and most private payers recognize the group treatment approach, providers can bill for individual patient follow-up visits for the evaluation and management services they deliver to each patient during a shared medical appointment (SMA).

“This is the good news. If you have 10 patients in an SMA that lasts 2 hours – 1 hour of which is with the physician – you can bill for 10 individual follow-up visits for evaluation and management services,” said Ms. Hodorowicz of Palos Heights, Ill.

For example, she said, if the reimbursement is $100 per patient, the physician will receive $1,000 for 1 hour of work. “Compare that to seeing 10 patients one on one in the traditional office setting, and spending about 20 minutes with each patient. It would take you more than 3 hours to make the same $1,000. In an SMA, this 1 hour translates to $17 a minute; the 3.3 hours in the office setting translates to 50 cents a minute. Do the math.”

But the SMA includes more than a clinical care component. Different programs have different formats, but evaluation, management, and medication titration are just part of a much more holistic package.

“Everyone who comes in gets a blood pressure check, a foot screen, and a retinal screen,” said Sharon Watts, a diabetes nurse practitioner who created an SMA program for the Louis Stokes Cleveland Veterans Affairs Medical Center. “The providers come in and give a brief talk on the importance of the [hemoglobin] A_1c, blood pressure, and LDL cholesterol, and we go through the rest of the ABCs of diabetes care. And we get out of there,” and let the educators and patients take over. Registered dieticians, diabetes educators, and behavioral specialists can all be part of the team. A 1-hour lecture, however, is not the goal.

“It is all patient driven,” said Susan Cornell, Pharm.D, a certified diabetes educator and pharmacist who helped create the SMA program at Midwestern University in Downers Grove, Ill. “We know it's going well when the patients – not the health care professionals – are doing most of the talking. Allowing the patients to take the lead is key, because we stress the importance of self-management. We want to make sure they take ownership of their condition. The more they do, the better they can control it.”

Unlike Ms. Watts' program, which focuses exclusively on high-risk patients, Dr. Cornell's CHAT (Collaborative Health Advocate Team) program includes patients of other risk levels who have been referred by their primary care provider. She makes sure to keep the groups homogeneous. “You really can't have type 1s, type 2s and 'gestationals' all in the same group because they have very different needs,” she said.

This program includes some clinical care, such as blood pressure checks and blood glucose levels, but it focuses more on self-management tools. Topics might include nutrition, medical therapy, cardiovascular disease, depression, self-monitoring of diabetes, or how to deal with complications.

Because it's within a university setting, CHAT is run by students who are supervised by the preceptors in their specialty, whether that's nutrition, psychology, pharmacology, or medicine.

The VA program has a slightly different take on the SMA. For example, Ms. Watts' program is not open to all comers. “I populate these groups myself,” she said at the meeting. “I want to go after those who aren't being gone after by anyone else – those who are at really high risk of problems.”

To enter this program, patients have to have an HbA_1c of at least 9%, a systolic blood pressure of at least 160 mm Hg, and an LDL cholesterol level of more than 140 mg/dL. Because it focuses on nonadherent, high-risk patients, this program has more clinical components.

When patients come in, they have some initial exams (blood pressure, foot, and retina screening) and get copies of their most recent labs, including HbA_1c, blood pressure, and LDL cholesterol. After a group review of diabetes-care issues, the ancillary staff takes over. Diet and nutrition, erectile dysfunction, mood disorders, barriers to care – any of these topics, and more, can become fodder for discussion. Open-ended questions from the facilitators usually help establish the group discussion themes.

During group time, patients are individually called into a separate room to review their labs, set treatment goals, and have their medications titrated. “Yes, there is a huge educational component to it, but this is not just an education class,” Ms. Watts said. “I want more. I want those blood sugars, blood pressures, and LDL numbers under control.”

She started the program in 2003, and her early assessments indicate that most patients (who attend about two or three sessions) are able to reduce their HbA_1c levels by 1%-2%. This improvement is directly related to increased medication adherence, Ms. Watts said.

Billing for the educational part of the SMA can be more than a little tricky, Ms. Hodorowicz said. “Medicare reimbursement for diabetes self-management training (DSMT) and medical nutrition therapy (MNT) is convoluted, confusing, complicated, and constantly changing.”

It's important to note that although Medicare does cover both DSMT and diabetes MNT, it will not pay for both when they are furnished on the same day to the same beneficiary. Although registered dieticians, certified diabetes educators, nurse practitioners, physician assistants, and others involved in the SMA can all bill for their services, either with their own national provider identification number or that of their group practice, Medicare requires some key codes for payment.

One of these is the five-digit diabetes ICD-9 diagnosis code. “This is really important on any claim you are billing,” she said. “Without a five-digit code to enhance the specificity of the diabetes diagnosis, you have a 99% chance that Medicare is going to deny that claim.”

For group DSMT, the procedure code is G0109, and time is billed in 30-minute units. But for this service to be covered by Medicare, the DSMT program has to be certified by the American Association of Diabetes Educators, the American Diabetes Association, or Indian Health Services.

Private payers also will cover group DSMT but may require different procedure codes. “It's best just to call them and ask what they want rather than guessing and getting a payment denied,” Ms. Hodorowicz said.

The procedure code for group diabetes MNT is 97804. Again, time is billed in 30-minute units. Registered dieticians who are Medicare providers are the only individuals who can furnish diabetes MNT and be reimbursed, although private practices, outpatient hospital departments, and some other entities also can bill on behalf of the dietician. Again, many private payers do cover MNT, but might require different procedure codes.

The SMA is an evidence-based practice paradigm that can work well for everyone involved, Ms. Hodorowicz said. “It's a highly effective way to deliver quality follow-up medical care and quality self-management education.”

Ms. Hodorowicz is on the faculty of the Johnson & Johnson Diabetes Institute, San Jose, Calif., and the DASPA (Diabetes Accreditation Standards–Practical Applications) program, which is sponsored jointly by the National Community Pharmacists Association and the American Association of Diabetes Educators; she also is on the speakers bureau of Nestle HealthCare Nutrition. Dr. Cornell is on the speakers bureau of Merck & Co. Inc., Abbott Diabetes Care, Novo Nordisk, the Johnson & Johnson Diabetes Institute, and Takeda Pharmaceutical Co.

Resources: A manual written by Ms. Watts describes how to establish and run a diabetes SMA program. Requests for the manual can be made to her at [email protected]www.maryannhodorowicz.com[email protected]

Session at DuPage Community Clinic in Wheaton, Ill. (L-R) Sarah Slater, pharmacy student 3rd year, and Tony Appello, pharmacy student 3rd year, presenting.

Source Courtesy Susan Cornell

ORLANDO – Shared medical appointments offer an effective way to manage patients with diabetes, providing them with personal and professional interactions that improve clinical outcomes and self-care as well as fostering personal growth.

The programs, which usually include seeing 5-15 patients during a 1.5- to 2-hour period, allow providers to maximize their teaching and clinical care time and can actually be a lucrative way of managing this population, Mary Ann Hodorowicz said.

This newer method for managing office patients with chronic conditions allows providers to maximize their clinical care and face-to-face time with their patients. Diabetes self-management training or medical nutrition therapy is also offered during the visit by a diabetes educator or a registered dietician; patients interact with one another to help further their learning.

Shared medical appointments are not only cost effective but also much more profitable in terms of payer reimbursement, compared with individual visits, said Ms. Hodorowicz, a certified diabetes educator and registered dietician who specializes in reimbursement for diabetes services.

“I'm the queen of acronyms, and 'MORE' is a great one to describe the shared medical appointment for diabetes care. You and your patients get MORE results: Maximization of Outcomes, Revenue, and Empowerment of patients.”

Because Medicare and most private payers recognize the group treatment approach, providers can bill for individual patient follow-up visits for the evaluation and management services they deliver to each patient during a shared medical appointment (SMA).

“This is the good news. If you have 10 patients in an SMA that lasts 2 hours – 1 hour of which is with the physician – you can bill for 10 individual follow-up visits for evaluation and management services,” said Ms. Hodorowicz of Palos Heights, Ill.

For example, she said, if the reimbursement is $100 per patient, the physician will receive $1,000 for 1 hour of work. “Compare that to seeing 10 patients one on one in the traditional office setting, and spending about 20 minutes with each patient. It would take you more than 3 hours to make the same $1,000. In an SMA, this 1 hour translates to $17 a minute; the 3.3 hours in the office setting translates to 50 cents a minute. Do the math.”

But the SMA includes more than a clinical care component. Different programs have different formats, but evaluation, management, and medication titration are just part of a much more holistic package.

“Everyone who comes in gets a blood pressure check, a foot screen, and a retinal screen,” said Sharon Watts, a diabetes nurse practitioner who created an SMA program for the Louis Stokes Cleveland Veterans Affairs Medical Center. “The providers come in and give a brief talk on the importance of the [hemoglobin] A_1c, blood pressure, and LDL cholesterol, and we go through the rest of the ABCs of diabetes care. And we get out of there,” and let the educators and patients take over. Registered dieticians, diabetes educators, and behavioral specialists can all be part of the team. A 1-hour lecture, however, is not the goal.

“It is all patient driven,” said Susan Cornell, Pharm.D, a certified diabetes educator and pharmacist who helped create the SMA program at Midwestern University in Downers Grove, Ill. “We know it's going well when the patients – not the health care professionals – are doing most of the talking. Allowing the patients to take the lead is key, because we stress the importance of self-management. We want to make sure they take ownership of their condition. The more they do, the better they can control it.”

Unlike Ms. Watts' program, which focuses exclusively on high-risk patients, Dr. Cornell's CHAT (Collaborative Health Advocate Team) program includes patients of other risk levels who have been referred by their primary care provider. She makes sure to keep the groups homogeneous. “You really can't have type 1s, type 2s and 'gestationals' all in the same group because they have very different needs,” she said.

This program includes some clinical care, such as blood pressure checks and blood glucose levels, but it focuses more on self-management tools. Topics might include nutrition, medical therapy, cardiovascular disease, depression, self-monitoring of diabetes, or how to deal with complications.

Because it's within a university setting, CHAT is run by students who are supervised by the preceptors in their specialty, whether that's nutrition, psychology, pharmacology, or medicine.

The VA program has a slightly different take on the SMA. For example, Ms. Watts' program is not open to all comers. “I populate these groups myself,” she said at the meeting. “I want to go after those who aren't being gone after by anyone else – those who are at really high risk of problems.”

To enter this program, patients have to have an HbA_1c of at least 9%, a systolic blood pressure of at least 160 mm Hg, and an LDL cholesterol level of more than 140 mg/dL. Because it focuses on nonadherent, high-risk patients, this program has more clinical components.

When patients come in, they have some initial exams (blood pressure, foot, and retina screening) and get copies of their most recent labs, including HbA_1c, blood pressure, and LDL cholesterol. After a group review of diabetes-care issues, the ancillary staff takes over. Diet and nutrition, erectile dysfunction, mood disorders, barriers to care – any of these topics, and more, can become fodder for discussion. Open-ended questions from the facilitators usually help establish the group discussion themes.

During group time, patients are individually called into a separate room to review their labs, set treatment goals, and have their medications titrated. “Yes, there is a huge educational component to it, but this is not just an education class,” Ms. Watts said. “I want more. I want those blood sugars, blood pressures, and LDL numbers under control.”

She started the program in 2003, and her early assessments indicate that most patients (who attend about two or three sessions) are able to reduce their HbA_1c levels by 1%-2%. This improvement is directly related to increased medication adherence, Ms. Watts said.

Billing for the educational part of the SMA can be more than a little tricky, Ms. Hodorowicz said. “Medicare reimbursement for diabetes self-management training (DSMT) and medical nutrition therapy (MNT) is convoluted, confusing, complicated, and constantly changing.”

It's important to note that although Medicare does cover both DSMT and diabetes MNT, it will not pay for both when they are furnished on the same day to the same beneficiary. Although registered dieticians, certified diabetes educators, nurse practitioners, physician assistants, and others involved in the SMA can all bill for their services, either with their own national provider identification number or that of their group practice, Medicare requires some key codes for payment.

One of these is the five-digit diabetes ICD-9 diagnosis code. “This is really important on any claim you are billing,” she said. “Without a five-digit code to enhance the specificity of the diabetes diagnosis, you have a 99% chance that Medicare is going to deny that claim.”

For group DSMT, the procedure code is G0109, and time is billed in 30-minute units. But for this service to be covered by Medicare, the DSMT program has to be certified by the American Association of Diabetes Educators, the American Diabetes Association, or Indian Health Services.

Private payers also will cover group DSMT but may require different procedure codes. “It's best just to call them and ask what they want rather than guessing and getting a payment denied,” Ms. Hodorowicz said.

The procedure code for group diabetes MNT is 97804. Again, time is billed in 30-minute units. Registered dieticians who are Medicare providers are the only individuals who can furnish diabetes MNT and be reimbursed, although private practices, outpatient hospital departments, and some other entities also can bill on behalf of the dietician. Again, many private payers do cover MNT, but might require different procedure codes.

The SMA is an evidence-based practice paradigm that can work well for everyone involved, Ms. Hodorowicz said. “It's a highly effective way to deliver quality follow-up medical care and quality self-management education.”

Ms. Hodorowicz is on the faculty of the Johnson & Johnson Diabetes Institute, San Jose, Calif., and the DASPA (Diabetes Accreditation Standards–Practical Applications) program, which is sponsored jointly by the National Community Pharmacists Association and the American Association of Diabetes Educators; she also is on the speakers bureau of Nestle HealthCare Nutrition. Dr. Cornell is on the speakers bureau of Merck & Co. Inc., Abbott Diabetes Care, Novo Nordisk, the Johnson & Johnson Diabetes Institute, and Takeda Pharmaceutical Co.

Resources: A manual written by Ms. Watts describes how to establish and run a diabetes SMA program. Requests for the manual can be made to her at [email protected]www.maryannhodorowicz.com[email protected]

Session at DuPage Community Clinic in Wheaton, Ill. (L-R) Sarah Slater, pharmacy student 3rd year, and Tony Appello, pharmacy student 3rd year, presenting.

Source Courtesy Susan Cornell

ORLANDO – Shared medical appointments offer an effective way to manage patients with diabetes, providing them with personal and professional interactions that improve clinical outcomes and self-care as well as fostering personal growth.

The programs, which usually include seeing 5-15 patients during a 1.5- to 2-hour period, allow providers to maximize their teaching and clinical care time and can actually be a lucrative way of managing this population, Mary Ann Hodorowicz said.

This newer method for managing office patients with chronic conditions allows providers to maximize their clinical care and face-to-face time with their patients. Diabetes self-management training or medical nutrition therapy is also offered during the visit by a diabetes educator or a registered dietician; patients interact with one another to help further their learning.

Shared medical appointments are not only cost effective but also much more profitable in terms of payer reimbursement, compared with individual visits, said Ms. Hodorowicz, a certified diabetes educator and registered dietician who specializes in reimbursement for diabetes services.

“I'm the queen of acronyms, and 'MORE' is a great one to describe the shared medical appointment for diabetes care. You and your patients get MORE results: Maximization of Outcomes, Revenue, and Empowerment of patients.”

Because Medicare and most private payers recognize the group treatment approach, providers can bill for individual patient follow-up visits for the evaluation and management services they deliver to each patient during a shared medical appointment (SMA).

“This is the good news. If you have 10 patients in an SMA that lasts 2 hours – 1 hour of which is with the physician – you can bill for 10 individual follow-up visits for evaluation and management services,” said Ms. Hodorowicz of Palos Heights, Ill.

For example, she said, if the reimbursement is $100 per patient, the physician will receive $1,000 for 1 hour of work. “Compare that to seeing 10 patients one on one in the traditional office setting, and spending about 20 minutes with each patient. It would take you more than 3 hours to make the same $1,000. In an SMA, this 1 hour translates to $17 a minute; the 3.3 hours in the office setting translates to 50 cents a minute. Do the math.”

But the SMA includes more than a clinical care component. Different programs have different formats, but evaluation, management, and medication titration are just part of a much more holistic package.

“Everyone who comes in gets a blood pressure check, a foot screen, and a retinal screen,” said Sharon Watts, a diabetes nurse practitioner who created an SMA program for the Louis Stokes Cleveland Veterans Affairs Medical Center. “The providers come in and give a brief talk on the importance of the [hemoglobin] A_1c, blood pressure, and LDL cholesterol, and we go through the rest of the ABCs of diabetes care. And we get out of there,” and let the educators and patients take over. Registered dieticians, diabetes educators, and behavioral specialists can all be part of the team. A 1-hour lecture, however, is not the goal.

“It is all patient driven,” said Susan Cornell, Pharm.D, a certified diabetes educator and pharmacist who helped create the SMA program at Midwestern University in Downers Grove, Ill. “We know it's going well when the patients – not the health care professionals – are doing most of the talking. Allowing the patients to take the lead is key, because we stress the importance of self-management. We want to make sure they take ownership of their condition. The more they do, the better they can control it.”

Unlike Ms. Watts' program, which focuses exclusively on high-risk patients, Dr. Cornell's CHAT (Collaborative Health Advocate Team) program includes patients of other risk levels who have been referred by their primary care provider. She makes sure to keep the groups homogeneous. “You really can't have type 1s, type 2s and 'gestationals' all in the same group because they have very different needs,” she said.

This program includes some clinical care, such as blood pressure checks and blood glucose levels, but it focuses more on self-management tools. Topics might include nutrition, medical therapy, cardiovascular disease, depression, self-monitoring of diabetes, or how to deal with complications.

Because it's within a university setting, CHAT is run by students who are supervised by the preceptors in their specialty, whether that's nutrition, psychology, pharmacology, or medicine.

The VA program has a slightly different take on the SMA. For example, Ms. Watts' program is not open to all comers. “I populate these groups myself,” she said at the meeting. “I want to go after those who aren't being gone after by anyone else – those who are at really high risk of problems.”

To enter this program, patients have to have an HbA_1c of at least 9%, a systolic blood pressure of at least 160 mm Hg, and an LDL cholesterol level of more than 140 mg/dL. Because it focuses on nonadherent, high-risk patients, this program has more clinical components.

When patients come in, they have some initial exams (blood pressure, foot, and retina screening) and get copies of their most recent labs, including HbA_1c, blood pressure, and LDL cholesterol. After a group review of diabetes-care issues, the ancillary staff takes over. Diet and nutrition, erectile dysfunction, mood disorders, barriers to care – any of these topics, and more, can become fodder for discussion. Open-ended questions from the facilitators usually help establish the group discussion themes.

During group time, patients are individually called into a separate room to review their labs, set treatment goals, and have their medications titrated. “Yes, there is a huge educational component to it, but this is not just an education class,” Ms. Watts said. “I want more. I want those blood sugars, blood pressures, and LDL numbers under control.”

She started the program in 2003, and her early assessments indicate that most patients (who attend about two or three sessions) are able to reduce their HbA_1c levels by 1%-2%. This improvement is directly related to increased medication adherence, Ms. Watts said.

Billing for the educational part of the SMA can be more than a little tricky, Ms. Hodorowicz said. “Medicare reimbursement for diabetes self-management training (DSMT) and medical nutrition therapy (MNT) is convoluted, confusing, complicated, and constantly changing.”

It's important to note that although Medicare does cover both DSMT and diabetes MNT, it will not pay for both when they are furnished on the same day to the same beneficiary. Although registered dieticians, certified diabetes educators, nurse practitioners, physician assistants, and others involved in the SMA can all bill for their services, either with their own national provider identification number or that of their group practice, Medicare requires some key codes for payment.

One of these is the five-digit diabetes ICD-9 diagnosis code. “This is really important on any claim you are billing,” she said. “Without a five-digit code to enhance the specificity of the diabetes diagnosis, you have a 99% chance that Medicare is going to deny that claim.”

For group DSMT, the procedure code is G0109, and time is billed in 30-minute units. But for this service to be covered by Medicare, the DSMT program has to be certified by the American Association of Diabetes Educators, the American Diabetes Association, or Indian Health Services.

Private payers also will cover group DSMT but may require different procedure codes. “It's best just to call them and ask what they want rather than guessing and getting a payment denied,” Ms. Hodorowicz said.

The procedure code for group diabetes MNT is 97804. Again, time is billed in 30-minute units. Registered dieticians who are Medicare providers are the only individuals who can furnish diabetes MNT and be reimbursed, although private practices, outpatient hospital departments, and some other entities also can bill on behalf of the dietician. Again, many private payers do cover MNT, but might require different procedure codes.

The SMA is an evidence-based practice paradigm that can work well for everyone involved, Ms. Hodorowicz said. “It's a highly effective way to deliver quality follow-up medical care and quality self-management education.”

Ms. Hodorowicz is on the faculty of the Johnson & Johnson Diabetes Institute, San Jose, Calif., and the DASPA (Diabetes Accreditation Standards–Practical Applications) program, which is sponsored jointly by the National Community Pharmacists Association and the American Association of Diabetes Educators; she also is on the speakers bureau of Nestle HealthCare Nutrition. Dr. Cornell is on the speakers bureau of Merck & Co. Inc., Abbott Diabetes Care, Novo Nordisk, the Johnson & Johnson Diabetes Institute, and Takeda Pharmaceutical Co.

Resources: A manual written by Ms. Watts describes how to establish and run a diabetes SMA program. Requests for the manual can be made to her at [email protected]www.maryannhodorowicz.com[email protected]

Session at DuPage Community Clinic in Wheaton, Ill. (L-R) Sarah Slater, pharmacy student 3rd year, and Tony Appello, pharmacy student 3rd year, presenting.

Source Courtesy Susan Cornell

Private and public sources are launching two massive efforts to identify biomarkers for Parkinson's disease – an effort they say will speed drug research, providing more efficient ways to track disease progress and monitor therapeutic response.

In late September, the Michael J. Fox Foundation kicked off its Parkinson's Progression Markers Initiative (PPMI) and the National Institute for Neurological Disorders and Stroke sent out a request for applications to create the Parkinson's Disease Biomarker Identification Network (PD-BIN). The 5-year PPMI is the first large-scale clinical study to focus exclusively on identifying and validating both chemical and imaging biomarkers of the disease. The multiproject PD-BIN will be similarly devoted to identifying biological markers that contribute to an individual's risk for Parkinson's disease, as well as its onset and progression, with the goal of speeding disease-modifying treatments.

“We expect that the biomarkers we discover will help us better understand the disease and accelerate therapeutic trials, with the goal of assessing whether a drug can modify the progression of Parkinson's,” PPMI primary investigator Dr. Kenneth Marek said in an interview. “In a way, this is much more complex than a clinical treatment trial. We are not testing a drug, but ideally, we will find markers that can pave the way to accomplish more effective drug testing.”

Speaking from the World Parkinson Congress in Glasgow, Scotland, where he unveiled the PPMI to the scientific community, Dr. Marek stressed the need for objective, measurable disease markers in diagnosis and disease progression, as well as in research studies. The diagnosis of Parkinson's disease remains solely based on clinical signs and symptoms, with no concrete diagnostic measure. Progression, as well, can be measured only by the worsening of symptoms. And with no objective clinical measurements in hand, researchers are “shooting in the dark” when assessing response to candidate drugs, he said.

“We have been conducting these clinical trials, but we there is no way to assess when a drug is ineffective,” said Dr. Marek, who also is president of the Institute for Neurodegenerative Disorders in New Haven, Conn.

Having a set of biomarkers will speed research in a way that is not now possible, said PPMI co-investigator Dr. Tanya Simuni, director of the Parkinson's Disease and Movement Disorders Center at Northwestern University, Chicago.

“We have many ongoing clinical trials of potential disease-modifying agents, but they are slow to progress because clinical assessment is the primary efficacy measure,” Dr. Simuni said in an interview. “Because of this, these studies take a long time and need a large number of patients – and they still sometimes end up with inconclusive results.” An objective measure of disease progression, would speed drug development by reducingthtudy duration and sizeof he said.

The discovery of a biomarker could also help clinicians identify patients in the earliest – perhaps even prodromal – disease state, she said. “By the time symptoms of Parkinson's appear, patients can have lost up to 70% of their dopamine-producing cells, which tells us that there is a prodromal or preclinical phase during which damage is occurring without clinical signs. Biomarkers could not only help us develop better interventions but also screening tools.”

The PPMI will be conducted at 14 U.S. centers and at centers in Innsbruck, Austria; Kassel and Tubingen, Germany; and Naples, Italy. It aims to recruit 200 healthy control patients and 400 patients newly diagnosed with Parkinson's disease who are not yet receiving medication.

The absence of Parkinson's disease medications is one key to a successful biomarker hunt, said Dr. Simuni, the principal investigator for the Midwestern region of the United States. “We want to make sure there is no over-signal of the therapy – that we are looking at the progression of disease unmasked by interventions.”

This should not be a problem with this patient population – at least initially. “For many patients with a new diagnosis, symptoms don't interfere with their function, so it's quite common not to start treatment at this time,” Dr. Simuni said. “At the point when the patient needs treatment, of course, it will start. They can remain in the study and count toward the follow-up. But our aim is to recruit patients early enough that we get at least 6 months of data without medication.”

Funding for the $40 million PPMI study will come from the Michael J. Fox Foundation, private contributions, Pfizer Inc., and – Dr. Marek hopes – federal grants.

In fact, he said, PPMI leaders hope to become involved in the PD-BIN.

Although the request for applications for the PD-BIN was just released (http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-11-005.html

“The deputy director of NINDS [Dr. Walter J. Koroshetz] made it clear that the goal of this project is to bring as many resources as possible to bear on advancing neuroprotective therapy for Parkinson's,” Dr. Hallett said in an interview.

Although not officially connected, the PD-BIN and the PPMI may join forces, Dr. Marek said.

“We'll be applying for [the federal project] and we would love for these processes to be complementary. We would be delighted to have the government, through NIH, partner with us.”

Both projects were largely inspired by the Alzheimer's Disease Neuroimaging Initiative (ADNI), which also is a public-private collaboration. Launched in 2004, the ADNI studied the rate of change of cognition, brain structure and function, and biomarkers in healthy control patients, patients with mild cognitive impairment, and patients with Alzheimer's disease. Discoveries made through the ADNI have shown that cerebrospinal fluid carries disease-specific biomarkers that change with disease progression, including levels of phosphorylated and unphosphorylated tau protein and amyloid-beta-42. The project also investigated new imaging compounds which allow, for the first time, visualization of amyloid plaques and tau neurofibrillary tangles in the brain and how they change during disease progression.

Like the ADNI, both the PPMI and the PD-BIN could amass an enormous bio-bank of samples, which will be available without cost to scientists with approved research projects. In fact, Dr. Marek said, PPMI data sets will be maintained by the same lab that administers ADNI data: the Laboratory of Neuroimaging at the University of California, Los Angeles.

PPMI already has specific biomarkers targeted for research. Preliminary data indicate that alpha-synuclein, urate, and expression of the Parkinson's genetic marker DJ-1 change according to disease stage. Some data suggest that total tau, phosphorylated tau, and amyloid-beta might change as cognitive function is altered. Therefore, each of the 12 study visits will include blood, cerebrospinal fluid, urine, and DNA sampling as well as motor, neuropsychiatric, and cognitive assessments.

Single-photo emission CT with DaTSCAN (ioflupane [123I]) and MRI imaging will determine changes in brain structure and dopamine levels. Although not yet approved for clinical use in the United States, the DaTSCAN radioisotope binds to dopamine transporters in the substantia nigra, allowing researchers to study dopaminergic neurodegeneration.

Dr. Simuni has served as a consultant and received honorarium from GE Healthcare, which manufactures and markets DaTSCAN in Europe. She has received research support from the NIH and the Michael J. Fox Foundation.

Dr. Marek is on the scientific advisory board of the Michael J. Fox Foundation and has been a consultant for Pfizer and GE Healthcare. He has an equity interest in Molecular NeuroImaging LLC. Dr. Hallet has no relevant disclosures.

PPMI will use single-photon emission CT scanning to track dopaminergic neurodegeneration in Parkinson's patients.

Source Courtesy Dr. John Seibyl, Institute for Neurodegenerative Disorders

How to Join the Biomarker Search

Recruitment is the first, second, and third issue in a study like this,” said PPMI lead investigator Dr. Kenneth Marek. “We know we are asking a lot of our participants, but from what we have seen so far, a lot of patients with Parkinson's, and their friends and families who could be controls, understand the need for this approach and are willing and excited about participating in it.”

Both Dr. Marek and his coinvestigator Dr. Tanya Simuni admitted that the repeat lumbar punctures the study calls for could intimidate potential subjects. “It's important that they know that for most people, the possible side effects of a lumbar puncture are just about the same as for a blood draw,” she said.

The first stop for information is the PPMI Web site,

www.ppmi-info.org

By clicking on the “For Physicians” button, doctors can download the Physician Tool Kit, which includes brochures about the study; a poster; a pocket card with the study overview; and research referral forms (

www.ppmi-info.org/about/for-physicians

Researchers who are interested in working with biological samples from the study also can find information about submitting requests for potential projects (

www.ppmi-info.org/for-researchers

The site contains a wealth of information for patients and families as well (

www.ppmi-info.org/about/for-pd-and-control-participants

Private and public sources are launching two massive efforts to identify biomarkers for Parkinson's disease – an effort they say will speed drug research, providing more efficient ways to track disease progress and monitor therapeutic response.

In late September, the Michael J. Fox Foundation kicked off its Parkinson's Progression Markers Initiative (PPMI) and the National Institute for Neurological Disorders and Stroke sent out a request for applications to create the Parkinson's Disease Biomarker Identification Network (PD-BIN). The 5-year PPMI is the first large-scale clinical study to focus exclusively on identifying and validating both chemical and imaging biomarkers of the disease. The multiproject PD-BIN will be similarly devoted to identifying biological markers that contribute to an individual's risk for Parkinson's disease, as well as its onset and progression, with the goal of speeding disease-modifying treatments.

“We expect that the biomarkers we discover will help us better understand the disease and accelerate therapeutic trials, with the goal of assessing whether a drug can modify the progression of Parkinson's,” PPMI primary investigator Dr. Kenneth Marek said in an interview. “In a way, this is much more complex than a clinical treatment trial. We are not testing a drug, but ideally, we will find markers that can pave the way to accomplish more effective drug testing.”

Speaking from the World Parkinson Congress in Glasgow, Scotland, where he unveiled the PPMI to the scientific community, Dr. Marek stressed the need for objective, measurable disease markers in diagnosis and disease progression, as well as in research studies. The diagnosis of Parkinson's disease remains solely based on clinical signs and symptoms, with no concrete diagnostic measure. Progression, as well, can be measured only by the worsening of symptoms. And with no objective clinical measurements in hand, researchers are “shooting in the dark” when assessing response to candidate drugs, he said.

“We have been conducting these clinical trials, but we there is no way to assess when a drug is ineffective,” said Dr. Marek, who also is president of the Institute for Neurodegenerative Disorders in New Haven, Conn.

Having a set of biomarkers will speed research in a way that is not now possible, said PPMI co-investigator Dr. Tanya Simuni, director of the Parkinson's Disease and Movement Disorders Center at Northwestern University, Chicago.

“We have many ongoing clinical trials of potential disease-modifying agents, but they are slow to progress because clinical assessment is the primary efficacy measure,” Dr. Simuni said in an interview. “Because of this, these studies take a long time and need a large number of patients – and they still sometimes end up with inconclusive results.” An objective measure of disease progression, would speed drug development by reducingthtudy duration and sizeof he said.

The discovery of a biomarker could also help clinicians identify patients in the earliest – perhaps even prodromal – disease state, she said. “By the time symptoms of Parkinson's appear, patients can have lost up to 70% of their dopamine-producing cells, which tells us that there is a prodromal or preclinical phase during which damage is occurring without clinical signs. Biomarkers could not only help us develop better interventions but also screening tools.”

The PPMI will be conducted at 14 U.S. centers and at centers in Innsbruck, Austria; Kassel and Tubingen, Germany; and Naples, Italy. It aims to recruit 200 healthy control patients and 400 patients newly diagnosed with Parkinson's disease who are not yet receiving medication.

The absence of Parkinson's disease medications is one key to a successful biomarker hunt, said Dr. Simuni, the principal investigator for the Midwestern region of the United States. “We want to make sure there is no over-signal of the therapy – that we are looking at the progression of disease unmasked by interventions.”

This should not be a problem with this patient population – at least initially. “For many patients with a new diagnosis, symptoms don't interfere with their function, so it's quite common not to start treatment at this time,” Dr. Simuni said. “At the point when the patient needs treatment, of course, it will start. They can remain in the study and count toward the follow-up. But our aim is to recruit patients early enough that we get at least 6 months of data without medication.”

Funding for the $40 million PPMI study will come from the Michael J. Fox Foundation, private contributions, Pfizer Inc., and – Dr. Marek hopes – federal grants.

In fact, he said, PPMI leaders hope to become involved in the PD-BIN.

Although the request for applications for the PD-BIN was just released (http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-11-005.html

“The deputy director of NINDS [Dr. Walter J. Koroshetz] made it clear that the goal of this project is to bring as many resources as possible to bear on advancing neuroprotective therapy for Parkinson's,” Dr. Hallett said in an interview.

Although not officially connected, the PD-BIN and the PPMI may join forces, Dr. Marek said.

“We'll be applying for [the federal project] and we would love for these processes to be complementary. We would be delighted to have the government, through NIH, partner with us.”

Both projects were largely inspired by the Alzheimer's Disease Neuroimaging Initiative (ADNI), which also is a public-private collaboration. Launched in 2004, the ADNI studied the rate of change of cognition, brain structure and function, and biomarkers in healthy control patients, patients with mild cognitive impairment, and patients with Alzheimer's disease. Discoveries made through the ADNI have shown that cerebrospinal fluid carries disease-specific biomarkers that change with disease progression, including levels of phosphorylated and unphosphorylated tau protein and amyloid-beta-42. The project also investigated new imaging compounds which allow, for the first time, visualization of amyloid plaques and tau neurofibrillary tangles in the brain and how they change during disease progression.

Like the ADNI, both the PPMI and the PD-BIN could amass an enormous bio-bank of samples, which will be available without cost to scientists with approved research projects. In fact, Dr. Marek said, PPMI data sets will be maintained by the same lab that administers ADNI data: the Laboratory of Neuroimaging at the University of California, Los Angeles.

PPMI already has specific biomarkers targeted for research. Preliminary data indicate that alpha-synuclein, urate, and expression of the Parkinson's genetic marker DJ-1 change according to disease stage. Some data suggest that total tau, phosphorylated tau, and amyloid-beta might change as cognitive function is altered. Therefore, each of the 12 study visits will include blood, cerebrospinal fluid, urine, and DNA sampling as well as motor, neuropsychiatric, and cognitive assessments.

Single-photo emission CT with DaTSCAN (ioflupane [123I]) and MRI imaging will determine changes in brain structure and dopamine levels. Although not yet approved for clinical use in the United States, the DaTSCAN radioisotope binds to dopamine transporters in the substantia nigra, allowing researchers to study dopaminergic neurodegeneration.

Dr. Simuni has served as a consultant and received honorarium from GE Healthcare, which manufactures and markets DaTSCAN in Europe. She has received research support from the NIH and the Michael J. Fox Foundation.

Dr. Marek is on the scientific advisory board of the Michael J. Fox Foundation and has been a consultant for Pfizer and GE Healthcare. He has an equity interest in Molecular NeuroImaging LLC. Dr. Hallet has no relevant disclosures.

PPMI will use single-photon emission CT scanning to track dopaminergic neurodegeneration in Parkinson's patients.

Source Courtesy Dr. John Seibyl, Institute for Neurodegenerative Disorders

How to Join the Biomarker Search

Recruitment is the first, second, and third issue in a study like this,” said PPMI lead investigator Dr. Kenneth Marek. “We know we are asking a lot of our participants, but from what we have seen so far, a lot of patients with Parkinson's, and their friends and families who could be controls, understand the need for this approach and are willing and excited about participating in it.”

Both Dr. Marek and his coinvestigator Dr. Tanya Simuni admitted that the repeat lumbar punctures the study calls for could intimidate potential subjects. “It's important that they know that for most people, the possible side effects of a lumbar puncture are just about the same as for a blood draw,” she said.

The first stop for information is the PPMI Web site,

www.ppmi-info.org

By clicking on the “For Physicians” button, doctors can download the Physician Tool Kit, which includes brochures about the study; a poster; a pocket card with the study overview; and research referral forms (

www.ppmi-info.org/about/for-physicians

Researchers who are interested in working with biological samples from the study also can find information about submitting requests for potential projects (

www.ppmi-info.org/for-researchers

The site contains a wealth of information for patients and families as well (

www.ppmi-info.org/about/for-pd-and-control-participants

Private and public sources are launching two massive efforts to identify biomarkers for Parkinson's disease – an effort they say will speed drug research, providing more efficient ways to track disease progress and monitor therapeutic response.

In late September, the Michael J. Fox Foundation kicked off its Parkinson's Progression Markers Initiative (PPMI) and the National Institute for Neurological Disorders and Stroke sent out a request for applications to create the Parkinson's Disease Biomarker Identification Network (PD-BIN). The 5-year PPMI is the first large-scale clinical study to focus exclusively on identifying and validating both chemical and imaging biomarkers of the disease. The multiproject PD-BIN will be similarly devoted to identifying biological markers that contribute to an individual's risk for Parkinson's disease, as well as its onset and progression, with the goal of speeding disease-modifying treatments.

“We expect that the biomarkers we discover will help us better understand the disease and accelerate therapeutic trials, with the goal of assessing whether a drug can modify the progression of Parkinson's,” PPMI primary investigator Dr. Kenneth Marek said in an interview. “In a way, this is much more complex than a clinical treatment trial. We are not testing a drug, but ideally, we will find markers that can pave the way to accomplish more effective drug testing.”

Speaking from the World Parkinson Congress in Glasgow, Scotland, where he unveiled the PPMI to the scientific community, Dr. Marek stressed the need for objective, measurable disease markers in diagnosis and disease progression, as well as in research studies. The diagnosis of Parkinson's disease remains solely based on clinical signs and symptoms, with no concrete diagnostic measure. Progression, as well, can be measured only by the worsening of symptoms. And with no objective clinical measurements in hand, researchers are “shooting in the dark” when assessing response to candidate drugs, he said.

“We have been conducting these clinical trials, but we there is no way to assess when a drug is ineffective,” said Dr. Marek, who also is president of the Institute for Neurodegenerative Disorders in New Haven, Conn.

Having a set of biomarkers will speed research in a way that is not now possible, said PPMI co-investigator Dr. Tanya Simuni, director of the Parkinson's Disease and Movement Disorders Center at Northwestern University, Chicago.

“We have many ongoing clinical trials of potential disease-modifying agents, but they are slow to progress because clinical assessment is the primary efficacy measure,” Dr. Simuni said in an interview. “Because of this, these studies take a long time and need a large number of patients – and they still sometimes end up with inconclusive results.” An objective measure of disease progression, would speed drug development by reducingthtudy duration and sizeof he said.

The discovery of a biomarker could also help clinicians identify patients in the earliest – perhaps even prodromal – disease state, she said. “By the time symptoms of Parkinson's appear, patients can have lost up to 70% of their dopamine-producing cells, which tells us that there is a prodromal or preclinical phase during which damage is occurring without clinical signs. Biomarkers could not only help us develop better interventions but also screening tools.”

The PPMI will be conducted at 14 U.S. centers and at centers in Innsbruck, Austria; Kassel and Tubingen, Germany; and Naples, Italy. It aims to recruit 200 healthy control patients and 400 patients newly diagnosed with Parkinson's disease who are not yet receiving medication.

The absence of Parkinson's disease medications is one key to a successful biomarker hunt, said Dr. Simuni, the principal investigator for the Midwestern region of the United States. “We want to make sure there is no over-signal of the therapy – that we are looking at the progression of disease unmasked by interventions.”

This should not be a problem with this patient population – at least initially. “For many patients with a new diagnosis, symptoms don't interfere with their function, so it's quite common not to start treatment at this time,” Dr. Simuni said. “At the point when the patient needs treatment, of course, it will start. They can remain in the study and count toward the follow-up. But our aim is to recruit patients early enough that we get at least 6 months of data without medication.”

Funding for the $40 million PPMI study will come from the Michael J. Fox Foundation, private contributions, Pfizer Inc., and – Dr. Marek hopes – federal grants.

In fact, he said, PPMI leaders hope to become involved in the PD-BIN.

Although the request for applications for the PD-BIN was just released (http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-11-005.html

“The deputy director of NINDS [Dr. Walter J. Koroshetz] made it clear that the goal of this project is to bring as many resources as possible to bear on advancing neuroprotective therapy for Parkinson's,” Dr. Hallett said in an interview.

Although not officially connected, the PD-BIN and the PPMI may join forces, Dr. Marek said.

“We'll be applying for [the federal project] and we would love for these processes to be complementary. We would be delighted to have the government, through NIH, partner with us.”

Both projects were largely inspired by the Alzheimer's Disease Neuroimaging Initiative (ADNI), which also is a public-private collaboration. Launched in 2004, the ADNI studied the rate of change of cognition, brain structure and function, and biomarkers in healthy control patients, patients with mild cognitive impairment, and patients with Alzheimer's disease. Discoveries made through the ADNI have shown that cerebrospinal fluid carries disease-specific biomarkers that change with disease progression, including levels of phosphorylated and unphosphorylated tau protein and amyloid-beta-42. The project also investigated new imaging compounds which allow, for the first time, visualization of amyloid plaques and tau neurofibrillary tangles in the brain and how they change during disease progression.

Like the ADNI, both the PPMI and the PD-BIN could amass an enormous bio-bank of samples, which will be available without cost to scientists with approved research projects. In fact, Dr. Marek said, PPMI data sets will be maintained by the same lab that administers ADNI data: the Laboratory of Neuroimaging at the University of California, Los Angeles.

PPMI already has specific biomarkers targeted for research. Preliminary data indicate that alpha-synuclein, urate, and expression of the Parkinson's genetic marker DJ-1 change according to disease stage. Some data suggest that total tau, phosphorylated tau, and amyloid-beta might change as cognitive function is altered. Therefore, each of the 12 study visits will include blood, cerebrospinal fluid, urine, and DNA sampling as well as motor, neuropsychiatric, and cognitive assessments.

Single-photo emission CT with DaTSCAN (ioflupane [123I]) and MRI imaging will determine changes in brain structure and dopamine levels. Although not yet approved for clinical use in the United States, the DaTSCAN radioisotope binds to dopamine transporters in the substantia nigra, allowing researchers to study dopaminergic neurodegeneration.

Dr. Simuni has served as a consultant and received honorarium from GE Healthcare, which manufactures and markets DaTSCAN in Europe. She has received research support from the NIH and the Michael J. Fox Foundation.

Dr. Marek is on the scientific advisory board of the Michael J. Fox Foundation and has been a consultant for Pfizer and GE Healthcare. He has an equity interest in Molecular NeuroImaging LLC. Dr. Hallet has no relevant disclosures.

PPMI will use single-photon emission CT scanning to track dopaminergic neurodegeneration in Parkinson's patients.

Source Courtesy Dr. John Seibyl, Institute for Neurodegenerative Disorders

How to Join the Biomarker Search

Recruitment is the first, second, and third issue in a study like this,” said PPMI lead investigator Dr. Kenneth Marek. “We know we are asking a lot of our participants, but from what we have seen so far, a lot of patients with Parkinson's, and their friends and families who could be controls, understand the need for this approach and are willing and excited about participating in it.”

Both Dr. Marek and his coinvestigator Dr. Tanya Simuni admitted that the repeat lumbar punctures the study calls for could intimidate potential subjects. “It's important that they know that for most people, the possible side effects of a lumbar puncture are just about the same as for a blood draw,” she said.

The first stop for information is the PPMI Web site,

www.ppmi-info.org

By clicking on the “For Physicians” button, doctors can download the Physician Tool Kit, which includes brochures about the study; a poster; a pocket card with the study overview; and research referral forms (

www.ppmi-info.org/about/for-physicians

Researchers who are interested in working with biological samples from the study also can find information about submitting requests for potential projects (

www.ppmi-info.org/for-researchers

The site contains a wealth of information for patients and families as well (

www.ppmi-info.org/about/for-pd-and-control-participants

Major Finding: Newer antiepileptic drugs that pose an increased risk of depression were associated with a significant increase in the odds of suicidal and self-harming behavior (odds ratio, 3.08).

Data Source: A nested, case-control study of 44,300 patients who took at least one AED in 1990-2005.

Disclosures: The study was sponsored by Bayer Schering Pharma, for which one investigator has served as a consultant. Two other investigators reported financial relationships with companies that manufacture AEDs.

Newer antiepileptic drugs that are associated with a high risk of depression may be the only agents in this class of medications that increase the risk of suicidal and self-harming behavior, according to a large, case-control study.

Epilepsy patients who took newer antiepileptic drugs (AEDs) with depressive side effects (levetiracetam, topiramate, tiagabine, and vigabatrin) had threefold greater odds of suicidal or self-harming behavior, compared with similar patients who did not use AEDs.

But a subanalysis of the cohort that looked at 15 different AEDs, including barbiturates and conventional drugs, found that only levetiracetam significantly increased the odds of suicidal behavior or self-harm (odds ratio, 6.4). The relationship between suicidal or self-harming behavior and the drugs topiramate and vigabatrin became nonsignificant in the subanalysis, according to the report published in Neurology.

The investigators, led by Dr. Frank Andersohn of Charité University Medical Center in Berlin, found that patients with preexisting psychiatric disorders may bear the brunt of these increased risks. “In our study the risk of self-harm or suicidal behavior observed for new AEDs with a high risk of depression was only evident in patients with, but not in those without, psychiatric comorbidity. This apparently differential AED effect with respect to psychiatric comorbidity was, however, not significant and may thus have been observed by chance alone.”

However, the investigators noted that the low number of cases reduced the study's power to detect significant interactions between psychiatric comorbidity and suicidal and self-harming behavior.

The study included up to 5 years of follow-up data on 44,300 patients with epilepsy who were treated with at least one AED during 1990-2005. All patients were included in the U.K. General Practice Research Database. The 453 cases of self-harming or suicidal behavior were matched by age and sex with 8,962 controls who had no such experience (Neurology 2010;75:335-40).

The entire cohort was approximately 52% male; the mean age was 36 years. Most (68%) had an undefined epilepsy type. Controls were significantly more likely to have psychiatric comorbidity, including a history of self-harm, antidepressant use, depression without treatment, psychotic disorder, mania, anxiety disorder, borderline personality disorder, alcohol dependence, and other substance abuse.

Of the 453 cases, 294 had attempted suicide and 159 had self-harmed. There were 78 patients who died initially or within 4 weeks of the onset of self-harm or suicidal behavior.

Of the entire group, 382 cases (84%) and 7,903 controls (88%) had been exposed to at least one AED in the year before the index date. For cases, the index date was the date of harm, but for controls it was the date that resulted in the same time of follow-up as the case to which that patient was matched. Within that time period, 62% of the cases and 72% of the controls were currently using the drugs.

Among the four new AEDs with a confirmed increased risk of depression, only current use was significantly associated with greater odds for suicidal or self-harming behavior. No significant relationship was seen with recent or past AED use.

In further analyses, Dr. Andersohn and his associates found that the relationship between self-harm and depression-inducing AEDs existed only in patients with a psychiatric disorder (OR, 8.48).

They also examined the risk associated with each individual AED. Self-harming or suicidal behaviors were not significantly associated with barbiturate AEDs (phenobarbital, primidone, and methylphenobarbital), conventional AEDs (carbamazepine, valproate, phenytoin, ethosuximide, and acetazolamide), or newer AEDs that do not carry an increased risk of depression (oxcarbazepine, lamotrigine, gabapentin, or pregabalin).

Among AEDs associated with depression, levetiracetam was the only agent associated with increased odds for self-harming or suicidal behavior. But this drug was taken by just two cases (0.4%) and eight controls (0.1%).

Dr. Andersohn and his colleagues noted that potential explanations of the biological relationship between AEDs and self-harm have been controversial.

“Drug-induced folate deficiency and enhanced GABA [gamma-aminobutyric acid] neurotransmission, especially in patients with hippocampal sclerosis, have been discussed as potential pharmacologic mechanisms of AED-induced depression and suicidality. However, contradictory data indicate that GABA-active agents can be effective in treating depression.”

In an editorial, Dr. Marco Mula and Dr. Josemir W. Sander suggested that other factors may be responsible for this apparent association. For much of the study period, the high-risk AEDs implicated were available only as add-on therapy in the United Kingdom, “suggesting that the exposed patients were receiving these drugs as part of polytherapy regimens. Therefore, these patients possibly had drug-refractory epilepsy, a group that is at the upper end of the suicide risk spectrum” (Neurology 2010;75:300-1).

Additionally, the study could not specifically identify the type of epilepsy for each patient. “In fact, the issue of suicidality in epilepsy needs to take into account all epilepsy variables, but mostly a careful examination of the mental state of the patients,” wrote Dr. Mula of the University Hospital Maggiore della Carità in Novara, Italy, and Dr. Sander of the University College London Institute of Neurology.

They noted that recent research suggests that a subgroup of epilepsy patients tends to develop psychiatric side effects whenever a new medication is introduced. “These people are usually drug-refractory, with a previous history, and often a family history, of psychotic disorders and may possibly have a functional abnormality in the limbic system” that predisposes them to self-harming behaviors.

Major Finding: Newer antiepileptic drugs that pose an increased risk of depression were associated with a significant increase in the odds of suicidal and self-harming behavior (odds ratio, 3.08).

Data Source: A nested, case-control study of 44,300 patients who took at least one AED in 1990-2005.

Disclosures: The study was sponsored by Bayer Schering Pharma, for which one investigator has served as a consultant. Two other investigators reported financial relationships with companies that manufacture AEDs.

Newer antiepileptic drugs that are associated with a high risk of depression may be the only agents in this class of medications that increase the risk of suicidal and self-harming behavior, according to a large, case-control study.

Epilepsy patients who took newer antiepileptic drugs (AEDs) with depressive side effects (levetiracetam, topiramate, tiagabine, and vigabatrin) had threefold greater odds of suicidal or self-harming behavior, compared with similar patients who did not use AEDs.

But a subanalysis of the cohort that looked at 15 different AEDs, including barbiturates and conventional drugs, found that only levetiracetam significantly increased the odds of suicidal behavior or self-harm (odds ratio, 6.4). The relationship between suicidal or self-harming behavior and the drugs topiramate and vigabatrin became nonsignificant in the subanalysis, according to the report published in Neurology.

The investigators, led by Dr. Frank Andersohn of Charité University Medical Center in Berlin, found that patients with preexisting psychiatric disorders may bear the brunt of these increased risks. “In our study the risk of self-harm or suicidal behavior observed for new AEDs with a high risk of depression was only evident in patients with, but not in those without, psychiatric comorbidity. This apparently differential AED effect with respect to psychiatric comorbidity was, however, not significant and may thus have been observed by chance alone.”

However, the investigators noted that the low number of cases reduced the study's power to detect significant interactions between psychiatric comorbidity and suicidal and self-harming behavior.

The study included up to 5 years of follow-up data on 44,300 patients with epilepsy who were treated with at least one AED during 1990-2005. All patients were included in the U.K. General Practice Research Database. The 453 cases of self-harming or suicidal behavior were matched by age and sex with 8,962 controls who had no such experience (Neurology 2010;75:335-40).

The entire cohort was approximately 52% male; the mean age was 36 years. Most (68%) had an undefined epilepsy type. Controls were significantly more likely to have psychiatric comorbidity, including a history of self-harm, antidepressant use, depression without treatment, psychotic disorder, mania, anxiety disorder, borderline personality disorder, alcohol dependence, and other substance abuse.

Of the 453 cases, 294 had attempted suicide and 159 had self-harmed. There were 78 patients who died initially or within 4 weeks of the onset of self-harm or suicidal behavior.

Of the entire group, 382 cases (84%) and 7,903 controls (88%) had been exposed to at least one AED in the year before the index date. For cases, the index date was the date of harm, but for controls it was the date that resulted in the same time of follow-up as the case to which that patient was matched. Within that time period, 62% of the cases and 72% of the controls were currently using the drugs.

Among the four new AEDs with a confirmed increased risk of depression, only current use was significantly associated with greater odds for suicidal or self-harming behavior. No significant relationship was seen with recent or past AED use.

In further analyses, Dr. Andersohn and his associates found that the relationship between self-harm and depression-inducing AEDs existed only in patients with a psychiatric disorder (OR, 8.48).

They also examined the risk associated with each individual AED. Self-harming or suicidal behaviors were not significantly associated with barbiturate AEDs (phenobarbital, primidone, and methylphenobarbital), conventional AEDs (carbamazepine, valproate, phenytoin, ethosuximide, and acetazolamide), or newer AEDs that do not carry an increased risk of depression (oxcarbazepine, lamotrigine, gabapentin, or pregabalin).

Among AEDs associated with depression, levetiracetam was the only agent associated with increased odds for self-harming or suicidal behavior. But this drug was taken by just two cases (0.4%) and eight controls (0.1%).

Dr. Andersohn and his colleagues noted that potential explanations of the biological relationship between AEDs and self-harm have been controversial.

“Drug-induced folate deficiency and enhanced GABA [gamma-aminobutyric acid] neurotransmission, especially in patients with hippocampal sclerosis, have been discussed as potential pharmacologic mechanisms of AED-induced depression and suicidality. However, contradictory data indicate that GABA-active agents can be effective in treating depression.”

In an editorial, Dr. Marco Mula and Dr. Josemir W. Sander suggested that other factors may be responsible for this apparent association. For much of the study period, the high-risk AEDs implicated were available only as add-on therapy in the United Kingdom, “suggesting that the exposed patients were receiving these drugs as part of polytherapy regimens. Therefore, these patients possibly had drug-refractory epilepsy, a group that is at the upper end of the suicide risk spectrum” (Neurology 2010;75:300-1).

Additionally, the study could not specifically identify the type of epilepsy for each patient. “In fact, the issue of suicidality in epilepsy needs to take into account all epilepsy variables, but mostly a careful examination of the mental state of the patients,” wrote Dr. Mula of the University Hospital Maggiore della Carità in Novara, Italy, and Dr. Sander of the University College London Institute of Neurology.

They noted that recent research suggests that a subgroup of epilepsy patients tends to develop psychiatric side effects whenever a new medication is introduced. “These people are usually drug-refractory, with a previous history, and often a family history, of psychotic disorders and may possibly have a functional abnormality in the limbic system” that predisposes them to self-harming behaviors.

Major Finding: Newer antiepileptic drugs that pose an increased risk of depression were associated with a significant increase in the odds of suicidal and self-harming behavior (odds ratio, 3.08).

Data Source: A nested, case-control study of 44,300 patients who took at least one AED in 1990-2005.

Disclosures: The study was sponsored by Bayer Schering Pharma, for which one investigator has served as a consultant. Two other investigators reported financial relationships with companies that manufacture AEDs.

Newer antiepileptic drugs that are associated with a high risk of depression may be the only agents in this class of medications that increase the risk of suicidal and self-harming behavior, according to a large, case-control study.

Epilepsy patients who took newer antiepileptic drugs (AEDs) with depressive side effects (levetiracetam, topiramate, tiagabine, and vigabatrin) had threefold greater odds of suicidal or self-harming behavior, compared with similar patients who did not use AEDs.

But a subanalysis of the cohort that looked at 15 different AEDs, including barbiturates and conventional drugs, found that only levetiracetam significantly increased the odds of suicidal behavior or self-harm (odds ratio, 6.4). The relationship between suicidal or self-harming behavior and the drugs topiramate and vigabatrin became nonsignificant in the subanalysis, according to the report published in Neurology.

The investigators, led by Dr. Frank Andersohn of Charité University Medical Center in Berlin, found that patients with preexisting psychiatric disorders may bear the brunt of these increased risks. “In our study the risk of self-harm or suicidal behavior observed for new AEDs with a high risk of depression was only evident in patients with, but not in those without, psychiatric comorbidity. This apparently differential AED effect with respect to psychiatric comorbidity was, however, not significant and may thus have been observed by chance alone.”

However, the investigators noted that the low number of cases reduced the study's power to detect significant interactions between psychiatric comorbidity and suicidal and self-harming behavior.

The study included up to 5 years of follow-up data on 44,300 patients with epilepsy who were treated with at least one AED during 1990-2005. All patients were included in the U.K. General Practice Research Database. The 453 cases of self-harming or suicidal behavior were matched by age and sex with 8,962 controls who had no such experience (Neurology 2010;75:335-40).

The entire cohort was approximately 52% male; the mean age was 36 years. Most (68%) had an undefined epilepsy type. Controls were significantly more likely to have psychiatric comorbidity, including a history of self-harm, antidepressant use, depression without treatment, psychotic disorder, mania, anxiety disorder, borderline personality disorder, alcohol dependence, and other substance abuse.

Of the 453 cases, 294 had attempted suicide and 159 had self-harmed. There were 78 patients who died initially or within 4 weeks of the onset of self-harm or suicidal behavior.

Of the entire group, 382 cases (84%) and 7,903 controls (88%) had been exposed to at least one AED in the year before the index date. For cases, the index date was the date of harm, but for controls it was the date that resulted in the same time of follow-up as the case to which that patient was matched. Within that time period, 62% of the cases and 72% of the controls were currently using the drugs.

Among the four new AEDs with a confirmed increased risk of depression, only current use was significantly associated with greater odds for suicidal or self-harming behavior. No significant relationship was seen with recent or past AED use.

In further analyses, Dr. Andersohn and his associates found that the relationship between self-harm and depression-inducing AEDs existed only in patients with a psychiatric disorder (OR, 8.48).

They also examined the risk associated with each individual AED. Self-harming or suicidal behaviors were not significantly associated with barbiturate AEDs (phenobarbital, primidone, and methylphenobarbital), conventional AEDs (carbamazepine, valproate, phenytoin, ethosuximide, and acetazolamide), or newer AEDs that do not carry an increased risk of depression (oxcarbazepine, lamotrigine, gabapentin, or pregabalin).

Among AEDs associated with depression, levetiracetam was the only agent associated with increased odds for self-harming or suicidal behavior. But this drug was taken by just two cases (0.4%) and eight controls (0.1%).

Dr. Andersohn and his colleagues noted that potential explanations of the biological relationship between AEDs and self-harm have been controversial.

“Drug-induced folate deficiency and enhanced GABA [gamma-aminobutyric acid] neurotransmission, especially in patients with hippocampal sclerosis, have been discussed as potential pharmacologic mechanisms of AED-induced depression and suicidality. However, contradictory data indicate that GABA-active agents can be effective in treating depression.”

In an editorial, Dr. Marco Mula and Dr. Josemir W. Sander suggested that other factors may be responsible for this apparent association. For much of the study period, the high-risk AEDs implicated were available only as add-on therapy in the United Kingdom, “suggesting that the exposed patients were receiving these drugs as part of polytherapy regimens. Therefore, these patients possibly had drug-refractory epilepsy, a group that is at the upper end of the suicide risk spectrum” (Neurology 2010;75:300-1).

Additionally, the study could not specifically identify the type of epilepsy for each patient. “In fact, the issue of suicidality in epilepsy needs to take into account all epilepsy variables, but mostly a careful examination of the mental state of the patients,” wrote Dr. Mula of the University Hospital Maggiore della Carità in Novara, Italy, and Dr. Sander of the University College London Institute of Neurology.

They noted that recent research suggests that a subgroup of epilepsy patients tends to develop psychiatric side effects whenever a new medication is introduced. “These people are usually drug-refractory, with a previous history, and often a family history, of psychotic disorders and may possibly have a functional abnormality in the limbic system” that predisposes them to self-harming behaviors.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.