Bruce Jancin

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one.

This key finding from a large, longitudinal, population-based Norwegian study has importance both for front-line clinicians as well as academic researchers, Dr. Lars J. Stovner observed at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it effectively not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache – that is, headache on an average of 15 or more days per month – may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trondelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3, compared with subjects without baseline chronic musculoskeletal pain in a multivariate analysis adjusted for the known potential confounders of age, gender, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed even higher, to 2.7-fold, when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain. They are both part of an entire pain matrix that is impaired."

Another HUNT analysis Dr. Stovner presented separately at the congress focused on the distinction between medication overuse headache and chronic daily headache without medication overuse. The study population consisted of 25,598 adults with no chronic daily headache in 1995-1997 at HUNT 2. Eleven years later, at the HUNT 3 follow-up, 201 subjects had developed medication overuse headache, for an incidence rate of 0.72 cases per 1,000 person-years.

"I think that’s perhaps a bit lower than would be expected from some of the retrospective studies done before in other countries, which suggest an incidence of medication overuse headache of 1%-1.5% per year," he noted.

Another 246 subjects developed chronic daily headache without medication overuse.

The key finding in this analysis was that several of the risk factors for development of medication overuse headache were not risk factors for chronic daily headache without medication overuse, indicating that these two disorders are pathogenetically distinct conditions, according to Dr. Stovner.

Shared risk factors for development of the two forms of chronic headache were female gender, having little education, chronic musculoskeletal complaints, insomnia, and headache at baseline.

In contrast, risk factors unique to the development of medication overuse headache included regular use of tranquilizers at baseline, which was associated with a 5.2-fold increased risk; a combination of gastrointestinal complaints, chronic musculoskeletal complaints, and anxiety and/or depression as defined by a Hospital Anxiety and Depression Scale score in excess of 11, which carried a 5-fold risk; smoking, which doubled the risk of subsequent medication overuse headache; and physical inactivity, which also was linked to a 2-fold elevated risk.

The implication of these findings is that the prevention and treatment of medication overuse headache should focus on the treatment of medical and psychiatric comorbid conditions, the use of tranquilizers, and lifestyle changes directed at smoking cessation and increased physical activity, Dr. Stovner concluded.

HUNT is supported by Norwegian governmental research funds. Dr. Stovner reported having no financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one.

This key finding from a large, longitudinal, population-based Norwegian study has importance both for front-line clinicians as well as academic researchers, Dr. Lars J. Stovner observed at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it effectively not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache – that is, headache on an average of 15 or more days per month – may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trondelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3, compared with subjects without baseline chronic musculoskeletal pain in a multivariate analysis adjusted for the known potential confounders of age, gender, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed even higher, to 2.7-fold, when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain. They are both part of an entire pain matrix that is impaired."

Another HUNT analysis Dr. Stovner presented separately at the congress focused on the distinction between medication overuse headache and chronic daily headache without medication overuse. The study population consisted of 25,598 adults with no chronic daily headache in 1995-1997 at HUNT 2. Eleven years later, at the HUNT 3 follow-up, 201 subjects had developed medication overuse headache, for an incidence rate of 0.72 cases per 1,000 person-years.

"I think that’s perhaps a bit lower than would be expected from some of the retrospective studies done before in other countries, which suggest an incidence of medication overuse headache of 1%-1.5% per year," he noted.

Another 246 subjects developed chronic daily headache without medication overuse.

The key finding in this analysis was that several of the risk factors for development of medication overuse headache were not risk factors for chronic daily headache without medication overuse, indicating that these two disorders are pathogenetically distinct conditions, according to Dr. Stovner.

Shared risk factors for development of the two forms of chronic headache were female gender, having little education, chronic musculoskeletal complaints, insomnia, and headache at baseline.

In contrast, risk factors unique to the development of medication overuse headache included regular use of tranquilizers at baseline, which was associated with a 5.2-fold increased risk; a combination of gastrointestinal complaints, chronic musculoskeletal complaints, and anxiety and/or depression as defined by a Hospital Anxiety and Depression Scale score in excess of 11, which carried a 5-fold risk; smoking, which doubled the risk of subsequent medication overuse headache; and physical inactivity, which also was linked to a 2-fold elevated risk.

The implication of these findings is that the prevention and treatment of medication overuse headache should focus on the treatment of medical and psychiatric comorbid conditions, the use of tranquilizers, and lifestyle changes directed at smoking cessation and increased physical activity, Dr. Stovner concluded.

HUNT is supported by Norwegian governmental research funds. Dr. Stovner reported having no financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one.

This key finding from a large, longitudinal, population-based Norwegian study has importance both for front-line clinicians as well as academic researchers, Dr. Lars J. Stovner observed at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it effectively not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache – that is, headache on an average of 15 or more days per month – may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trondelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3, compared with subjects without baseline chronic musculoskeletal pain in a multivariate analysis adjusted for the known potential confounders of age, gender, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed even higher, to 2.7-fold, when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain. They are both part of an entire pain matrix that is impaired."

Another HUNT analysis Dr. Stovner presented separately at the congress focused on the distinction between medication overuse headache and chronic daily headache without medication overuse. The study population consisted of 25,598 adults with no chronic daily headache in 1995-1997 at HUNT 2. Eleven years later, at the HUNT 3 follow-up, 201 subjects had developed medication overuse headache, for an incidence rate of 0.72 cases per 1,000 person-years.

"I think that’s perhaps a bit lower than would be expected from some of the retrospective studies done before in other countries, which suggest an incidence of medication overuse headache of 1%-1.5% per year," he noted.

Another 246 subjects developed chronic daily headache without medication overuse.

The key finding in this analysis was that several of the risk factors for development of medication overuse headache were not risk factors for chronic daily headache without medication overuse, indicating that these two disorders are pathogenetically distinct conditions, according to Dr. Stovner.

Shared risk factors for development of the two forms of chronic headache were female gender, having little education, chronic musculoskeletal complaints, insomnia, and headache at baseline.

In contrast, risk factors unique to the development of medication overuse headache included regular use of tranquilizers at baseline, which was associated with a 5.2-fold increased risk; a combination of gastrointestinal complaints, chronic musculoskeletal complaints, and anxiety and/or depression as defined by a Hospital Anxiety and Depression Scale score in excess of 11, which carried a 5-fold risk; smoking, which doubled the risk of subsequent medication overuse headache; and physical inactivity, which also was linked to a 2-fold elevated risk.

The implication of these findings is that the prevention and treatment of medication overuse headache should focus on the treatment of medical and psychiatric comorbid conditions, the use of tranquilizers, and lifestyle changes directed at smoking cessation and increased physical activity, Dr. Stovner concluded.

HUNT is supported by Norwegian governmental research funds. Dr. Stovner reported having no financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one, according to Dr. Lars J. Stovner.

This key finding from an impressively large, longitudinal, population-based Norwegian study has importance both for frontline clinicians as well as academic researchers, he said at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trøndelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3 compared with subjects without baseline chronic musculoskeletal pain, in a multivariate analysis adjusted for the known potential confounders of age, sex, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed to 2.7-fold when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"Chronic daily headache and chronic musculoskeletal complaints are enormous public health problems. This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain; they are both part of an entire pain matrix that is impaired."

The HUNT study is supported by Norwegian governmental research funds. Dr. Stovner reported having no relevant financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one, according to Dr. Lars J. Stovner.

This key finding from an impressively large, longitudinal, population-based Norwegian study has importance both for frontline clinicians as well as academic researchers, he said at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trøndelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3 compared with subjects without baseline chronic musculoskeletal pain, in a multivariate analysis adjusted for the known potential confounders of age, sex, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed to 2.7-fold when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"Chronic daily headache and chronic musculoskeletal complaints are enormous public health problems. This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain; they are both part of an entire pain matrix that is impaired."

The HUNT study is supported by Norwegian governmental research funds. Dr. Stovner reported having no relevant financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one, according to Dr. Lars J. Stovner.

This key finding from an impressively large, longitudinal, population-based Norwegian study has importance both for frontline clinicians as well as academic researchers, he said at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trøndelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3 compared with subjects without baseline chronic musculoskeletal pain, in a multivariate analysis adjusted for the known potential confounders of age, sex, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed to 2.7-fold when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"Chronic daily headache and chronic musculoskeletal complaints are enormous public health problems. This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain; they are both part of an entire pain matrix that is impaired."

The HUNT study is supported by Norwegian governmental research funds. Dr. Stovner reported having no relevant financial conflicts.

LONDON – Depression in patients with episodic migraine is an independent risk factor for transformation of their headache pattern into far more burdensome chronic migraine, according to data from the landmark American Migraine Prevalence and Prevention study.

"The study indicates that we need to look for depression in patients with episodic migraine or chronic migraine. We need to take it seriously and address this issue with patients – make the referral to a psychiatrist or treat them yourself if you’re comfortable with that. And the depression should be addressed as a problem separate from the headaches," Dr. Sait Ashina said at the European Headache and Migraine Trust International Congress.

AMPP study participants who had episodic migraine and depression were 1.65-fold more likely to progress to chronic migraine within the next year than were nondepressed participants who had episodic migraine, in an analysis extensively adjusted for potential confounding variables, reported Dr. Ashina of Albert Einstein School of Medicine, New York.

Moreover, a dose-response relationship was evident between depression severity and risk of progression from episodic to chronic migraine. That is, the nearly 1,400 AMPP participants with episodic migraine and moderate depression as defined by a Patient Health Questionnaire–9 (PHQ-9) score of 10-14 out of a maximum possible 27 had an adjusted 1.77-fold greater risk of converting to chronic migraine within the next year than did the 10,898 episodic migraine sufferers with no or mild depression, while the 656 with moderately severe depression as evidenced by a PHQ-9 score of 15-19 had a 2.35-fold increased risk, and the 420 individuals with a PHQ-9 score of 20-27 were at 2.53-fold increased risk.

The AMPP study is an ongoing longitudinal, population-based study in which 24,000 adults with severe headache were surveyed annually during 2004-2009. Dr. Ashina’s analysis involved nearly 13,500 participants who met criteria for episodic migraine in the 2005 or 2006 surveys. Transformation from episodic to chronic migraine within the next year occurred in 2.4% of the 2005 cohort and 2.2% of the 2006 group. Episodic migraine was defined in standard fashion as migraine headaches occurring on not more than 14 days per month averaged over the past 3 months, while chronic migraine entailed headaches on an average of 15 or more days per month.

The depression/migraine chronification analysis was adjusted for cutaneous allodynia, physician diagnosis of an anxiety disorder, headache pain intensity, headache frequency, migraine symptom score, use of antidepressant medications, headache-driven medication overuse, age, sex, body mass index, income, and health insurance status. The two strongest predictors of migraine chronification in the multivariate analysis proved to be depression and medication overuse involving triptans and/or opioids.

Dr. Ashina said that prior studies have established that depression and migraine are cotravelers, and that the relationship is bidirectional: That is, migraine is a risk factor for new-onset depression, and depression is a risk factor for new-onset migraine.

For example, one classic study conducted by some of the coinvestigators in Dr. Ashina’s current AMPP analysis showed a 2-year incidence of new-onset migraine of 9.3% in patients with major depression, compared with 2.9% in controls without major depression (odds ratio, 3.4). There also was a 2-year incidence of new-onset depression of 10.5% in migraineurs, compared with 2% in controls without migraine or other severe headache, for an odds ratio of 5.8 (Neurology 2003;60:1,308-12).

And in a combined analysis of two other studies, the prevalence of depression as defined using the PHQ-9 was 9.2% in the general population, 17.2% in persons with episodic migraine, and 30.2% in those with chronic migraine.

However, the relationship between depression and transformation of episodic to chronic migraine hasn’t previously been carefully looked at, which was the impetus for the AMPP analysis, he explained.

Back transitions from chronic to episodic migraine are known to be common, occurring in roughly one-quarter of patients with chronic migraine per year. Whether effective treatment of depression in chronic migraine patients promotes back transition to episodic migraine, or for that matter, whether antidepressant therapy in patients with episodic migraine reduces the risk of transformation to chronic migraine, are unanswered questions – and priorities for further research, in Dr. Ashina’s view.

At the international congress, Dr. Ashina received the prestigious Enrico Greppi Award from the Italian Society for the Study of Headaches for his research.

The AMPP study is funded by a grant from Ortho-McNeil Neurologics. Dr. Ashina’s analysis received supplemental funding in the form of a research grant from Allergan. He reported having served as a consultant to NeurogesX and Depomed.

LONDON – Depression in patients with episodic migraine is an independent risk factor for transformation of their headache pattern into far more burdensome chronic migraine, according to data from the landmark American Migraine Prevalence and Prevention study.

"The study indicates that we need to look for depression in patients with episodic migraine or chronic migraine. We need to take it seriously and address this issue with patients – make the referral to a psychiatrist or treat them yourself if you’re comfortable with that. And the depression should be addressed as a problem separate from the headaches," Dr. Sait Ashina said at the European Headache and Migraine Trust International Congress.

AMPP study participants who had episodic migraine and depression were 1.65-fold more likely to progress to chronic migraine within the next year than were nondepressed participants who had episodic migraine, in an analysis extensively adjusted for potential confounding variables, reported Dr. Ashina of Albert Einstein School of Medicine, New York.

Moreover, a dose-response relationship was evident between depression severity and risk of progression from episodic to chronic migraine. That is, the nearly 1,400 AMPP participants with episodic migraine and moderate depression as defined by a Patient Health Questionnaire–9 (PHQ-9) score of 10-14 out of a maximum possible 27 had an adjusted 1.77-fold greater risk of converting to chronic migraine within the next year than did the 10,898 episodic migraine sufferers with no or mild depression, while the 656 with moderately severe depression as evidenced by a PHQ-9 score of 15-19 had a 2.35-fold increased risk, and the 420 individuals with a PHQ-9 score of 20-27 were at 2.53-fold increased risk.

The AMPP study is an ongoing longitudinal, population-based study in which 24,000 adults with severe headache were surveyed annually during 2004-2009. Dr. Ashina’s analysis involved nearly 13,500 participants who met criteria for episodic migraine in the 2005 or 2006 surveys. Transformation from episodic to chronic migraine within the next year occurred in 2.4% of the 2005 cohort and 2.2% of the 2006 group. Episodic migraine was defined in standard fashion as migraine headaches occurring on not more than 14 days per month averaged over the past 3 months, while chronic migraine entailed headaches on an average of 15 or more days per month.

The depression/migraine chronification analysis was adjusted for cutaneous allodynia, physician diagnosis of an anxiety disorder, headache pain intensity, headache frequency, migraine symptom score, use of antidepressant medications, headache-driven medication overuse, age, sex, body mass index, income, and health insurance status. The two strongest predictors of migraine chronification in the multivariate analysis proved to be depression and medication overuse involving triptans and/or opioids.

Dr. Ashina said that prior studies have established that depression and migraine are cotravelers, and that the relationship is bidirectional: That is, migraine is a risk factor for new-onset depression, and depression is a risk factor for new-onset migraine.

For example, one classic study conducted by some of the coinvestigators in Dr. Ashina’s current AMPP analysis showed a 2-year incidence of new-onset migraine of 9.3% in patients with major depression, compared with 2.9% in controls without major depression (odds ratio, 3.4). There also was a 2-year incidence of new-onset depression of 10.5% in migraineurs, compared with 2% in controls without migraine or other severe headache, for an odds ratio of 5.8 (Neurology 2003;60:1,308-12).

And in a combined analysis of two other studies, the prevalence of depression as defined using the PHQ-9 was 9.2% in the general population, 17.2% in persons with episodic migraine, and 30.2% in those with chronic migraine.

However, the relationship between depression and transformation of episodic to chronic migraine hasn’t previously been carefully looked at, which was the impetus for the AMPP analysis, he explained.

Back transitions from chronic to episodic migraine are known to be common, occurring in roughly one-quarter of patients with chronic migraine per year. Whether effective treatment of depression in chronic migraine patients promotes back transition to episodic migraine, or for that matter, whether antidepressant therapy in patients with episodic migraine reduces the risk of transformation to chronic migraine, are unanswered questions – and priorities for further research, in Dr. Ashina’s view.

At the international congress, Dr. Ashina received the prestigious Enrico Greppi Award from the Italian Society for the Study of Headaches for his research.

The AMPP study is funded by a grant from Ortho-McNeil Neurologics. Dr. Ashina’s analysis received supplemental funding in the form of a research grant from Allergan. He reported having served as a consultant to NeurogesX and Depomed.

LONDON – Depression in patients with episodic migraine is an independent risk factor for transformation of their headache pattern into far more burdensome chronic migraine, according to data from the landmark American Migraine Prevalence and Prevention study.

"The study indicates that we need to look for depression in patients with episodic migraine or chronic migraine. We need to take it seriously and address this issue with patients – make the referral to a psychiatrist or treat them yourself if you’re comfortable with that. And the depression should be addressed as a problem separate from the headaches," Dr. Sait Ashina said at the European Headache and Migraine Trust International Congress.

AMPP study participants who had episodic migraine and depression were 1.65-fold more likely to progress to chronic migraine within the next year than were nondepressed participants who had episodic migraine, in an analysis extensively adjusted for potential confounding variables, reported Dr. Ashina of Albert Einstein School of Medicine, New York.

Moreover, a dose-response relationship was evident between depression severity and risk of progression from episodic to chronic migraine. That is, the nearly 1,400 AMPP participants with episodic migraine and moderate depression as defined by a Patient Health Questionnaire–9 (PHQ-9) score of 10-14 out of a maximum possible 27 had an adjusted 1.77-fold greater risk of converting to chronic migraine within the next year than did the 10,898 episodic migraine sufferers with no or mild depression, while the 656 with moderately severe depression as evidenced by a PHQ-9 score of 15-19 had a 2.35-fold increased risk, and the 420 individuals with a PHQ-9 score of 20-27 were at 2.53-fold increased risk.

The AMPP study is an ongoing longitudinal, population-based study in which 24,000 adults with severe headache were surveyed annually during 2004-2009. Dr. Ashina’s analysis involved nearly 13,500 participants who met criteria for episodic migraine in the 2005 or 2006 surveys. Transformation from episodic to chronic migraine within the next year occurred in 2.4% of the 2005 cohort and 2.2% of the 2006 group. Episodic migraine was defined in standard fashion as migraine headaches occurring on not more than 14 days per month averaged over the past 3 months, while chronic migraine entailed headaches on an average of 15 or more days per month.

The depression/migraine chronification analysis was adjusted for cutaneous allodynia, physician diagnosis of an anxiety disorder, headache pain intensity, headache frequency, migraine symptom score, use of antidepressant medications, headache-driven medication overuse, age, sex, body mass index, income, and health insurance status. The two strongest predictors of migraine chronification in the multivariate analysis proved to be depression and medication overuse involving triptans and/or opioids.

Dr. Ashina said that prior studies have established that depression and migraine are cotravelers, and that the relationship is bidirectional: That is, migraine is a risk factor for new-onset depression, and depression is a risk factor for new-onset migraine.

For example, one classic study conducted by some of the coinvestigators in Dr. Ashina’s current AMPP analysis showed a 2-year incidence of new-onset migraine of 9.3% in patients with major depression, compared with 2.9% in controls without major depression (odds ratio, 3.4). There also was a 2-year incidence of new-onset depression of 10.5% in migraineurs, compared with 2% in controls without migraine or other severe headache, for an odds ratio of 5.8 (Neurology 2003;60:1,308-12).

And in a combined analysis of two other studies, the prevalence of depression as defined using the PHQ-9 was 9.2% in the general population, 17.2% in persons with episodic migraine, and 30.2% in those with chronic migraine.

However, the relationship between depression and transformation of episodic to chronic migraine hasn’t previously been carefully looked at, which was the impetus for the AMPP analysis, he explained.

Back transitions from chronic to episodic migraine are known to be common, occurring in roughly one-quarter of patients with chronic migraine per year. Whether effective treatment of depression in chronic migraine patients promotes back transition to episodic migraine, or for that matter, whether antidepressant therapy in patients with episodic migraine reduces the risk of transformation to chronic migraine, are unanswered questions – and priorities for further research, in Dr. Ashina’s view.

At the international congress, Dr. Ashina received the prestigious Enrico Greppi Award from the Italian Society for the Study of Headaches for his research.

The AMPP study is funded by a grant from Ortho-McNeil Neurologics. Dr. Ashina’s analysis received supplemental funding in the form of a research grant from Allergan. He reported having served as a consultant to NeurogesX and Depomed.

LONDON – Brief low-temperature radiofrequency rhizolysis of the C-1 spinal nerve and C-2 and C-3 dorsal root ganglia was safe and effective for occipital neuralgia with migraine in a retrospective series of 10 patients.

"The pain reduction lasted for an average of 5½ months. That’s a longer duration of action than with nerve blockade alone," said Dr. Mollie M. Johnston of the headache research and treatment program at the University of California, Los Angeles (UCLA).

While the favorable initial clinical experience with this novel therapy is exciting, the broader significance of the findings lies in a resultant new appreciation of the C-1 nerve root as likely an important player in pain syndromes involving an orbital or periorbital distribution.

"The C-1 nerve root may be an important target for pain syndromes such as occipital neuralgia, migraine, and possibly cluster headache. This target may not be addressed by approaches currently in widespread use," she said at the European Headache and Migraine Trust International Congress.

The C-1 nerve root has traditionally not been thought of as having a significant sensory function because it doesn’t have dermatomal or cutaneous branches. But recent cadaveric studies have demonstrated that up to half of individuals have C-1 dorsal root ganglia, which typically lie medial to the dural root sleeve and inferior to the vertebral artery. Moreover, persons without C-1 dorsal root ganglia often have C-1 rootlets joining the spinal accessory nerve (J. Neurosurgery 2011;115:929-33). These cadaveric findings suggest a sensory function for the C-1 nerve root; however, until Dr. Johnston’s study, the pain referral pattern associated with this sensory function wasn’t known.

It’s well established that the dorsal rami of the C-2 and C-3 nerve roots contribute to the auricular nerve, the greater and lesser occipital nerves, and the third occipital nerve. These nerves are known to send sensory input from the occipital region to the periauricular region, the vertex, the C-2 and C-3 facet joints, and the cervical musculature, which is why they, too, were targeted for rhizolysis, Dr. Johnston explained.

The novel treatment for occipital neuralgia she and her coworkers have developed at UCLA entails a two-step neurosurgical procedure. First comes fluoroscopically guided provocation testing at the C-1 through C-3 level, followed by blockage of the nerve roots with anesthetic plus steroids. In a later separate procedure, the surgeon performs brief low-temperature radiofrequency rhizolysis.

Dr. Johnston presented a retrospective series of 10 patients with the distinctive, burning electricaltype pain of occipital neuralgia, 6 of whom also had migraine. The patients with migraine experienced orbital or periorbital pain referral upon direct stimulation at the C-1 level; those without migraine did not.

Nine of 10 patients had a positive nerve block, with either transient or sustained pain relief. The seven patients who didn’t experience sustained pain relief as a result of C-1, -2, and -3 nerve blockade subsequently underwent brief low-temperature radiofrequency rhizolysis. Four of the seven responded with a greater than 50% reduction in pain, headache days, and need for rescue medications; their responses lasted for an average of 5.5 months. The other three patients had a lesser response or no response.

No side effects or complications occurred as a consequence of the procedure. Future controlled studies are planned.

Dr. Johnston reported having no relevant financial disclosures.

LONDON – Brief low-temperature radiofrequency rhizolysis of the C-1 spinal nerve and C-2 and C-3 dorsal root ganglia was safe and effective for occipital neuralgia with migraine in a retrospective series of 10 patients.

"The pain reduction lasted for an average of 5½ months. That’s a longer duration of action than with nerve blockade alone," said Dr. Mollie M. Johnston of the headache research and treatment program at the University of California, Los Angeles (UCLA).

While the favorable initial clinical experience with this novel therapy is exciting, the broader significance of the findings lies in a resultant new appreciation of the C-1 nerve root as likely an important player in pain syndromes involving an orbital or periorbital distribution.

"The C-1 nerve root may be an important target for pain syndromes such as occipital neuralgia, migraine, and possibly cluster headache. This target may not be addressed by approaches currently in widespread use," she said at the European Headache and Migraine Trust International Congress.

The C-1 nerve root has traditionally not been thought of as having a significant sensory function because it doesn’t have dermatomal or cutaneous branches. But recent cadaveric studies have demonstrated that up to half of individuals have C-1 dorsal root ganglia, which typically lie medial to the dural root sleeve and inferior to the vertebral artery. Moreover, persons without C-1 dorsal root ganglia often have C-1 rootlets joining the spinal accessory nerve (J. Neurosurgery 2011;115:929-33). These cadaveric findings suggest a sensory function for the C-1 nerve root; however, until Dr. Johnston’s study, the pain referral pattern associated with this sensory function wasn’t known.

It’s well established that the dorsal rami of the C-2 and C-3 nerve roots contribute to the auricular nerve, the greater and lesser occipital nerves, and the third occipital nerve. These nerves are known to send sensory input from the occipital region to the periauricular region, the vertex, the C-2 and C-3 facet joints, and the cervical musculature, which is why they, too, were targeted for rhizolysis, Dr. Johnston explained.

The novel treatment for occipital neuralgia she and her coworkers have developed at UCLA entails a two-step neurosurgical procedure. First comes fluoroscopically guided provocation testing at the C-1 through C-3 level, followed by blockage of the nerve roots with anesthetic plus steroids. In a later separate procedure, the surgeon performs brief low-temperature radiofrequency rhizolysis.

Dr. Johnston presented a retrospective series of 10 patients with the distinctive, burning electricaltype pain of occipital neuralgia, 6 of whom also had migraine. The patients with migraine experienced orbital or periorbital pain referral upon direct stimulation at the C-1 level; those without migraine did not.

Nine of 10 patients had a positive nerve block, with either transient or sustained pain relief. The seven patients who didn’t experience sustained pain relief as a result of C-1, -2, and -3 nerve blockade subsequently underwent brief low-temperature radiofrequency rhizolysis. Four of the seven responded with a greater than 50% reduction in pain, headache days, and need for rescue medications; their responses lasted for an average of 5.5 months. The other three patients had a lesser response or no response.

No side effects or complications occurred as a consequence of the procedure. Future controlled studies are planned.

Dr. Johnston reported having no relevant financial disclosures.

LONDON – Brief low-temperature radiofrequency rhizolysis of the C-1 spinal nerve and C-2 and C-3 dorsal root ganglia was safe and effective for occipital neuralgia with migraine in a retrospective series of 10 patients.

"The pain reduction lasted for an average of 5½ months. That’s a longer duration of action than with nerve blockade alone," said Dr. Mollie M. Johnston of the headache research and treatment program at the University of California, Los Angeles (UCLA).

While the favorable initial clinical experience with this novel therapy is exciting, the broader significance of the findings lies in a resultant new appreciation of the C-1 nerve root as likely an important player in pain syndromes involving an orbital or periorbital distribution.

"The C-1 nerve root may be an important target for pain syndromes such as occipital neuralgia, migraine, and possibly cluster headache. This target may not be addressed by approaches currently in widespread use," she said at the European Headache and Migraine Trust International Congress.

The C-1 nerve root has traditionally not been thought of as having a significant sensory function because it doesn’t have dermatomal or cutaneous branches. But recent cadaveric studies have demonstrated that up to half of individuals have C-1 dorsal root ganglia, which typically lie medial to the dural root sleeve and inferior to the vertebral artery. Moreover, persons without C-1 dorsal root ganglia often have C-1 rootlets joining the spinal accessory nerve (J. Neurosurgery 2011;115:929-33). These cadaveric findings suggest a sensory function for the C-1 nerve root; however, until Dr. Johnston’s study, the pain referral pattern associated with this sensory function wasn’t known.

It’s well established that the dorsal rami of the C-2 and C-3 nerve roots contribute to the auricular nerve, the greater and lesser occipital nerves, and the third occipital nerve. These nerves are known to send sensory input from the occipital region to the periauricular region, the vertex, the C-2 and C-3 facet joints, and the cervical musculature, which is why they, too, were targeted for rhizolysis, Dr. Johnston explained.

The novel treatment for occipital neuralgia she and her coworkers have developed at UCLA entails a two-step neurosurgical procedure. First comes fluoroscopically guided provocation testing at the C-1 through C-3 level, followed by blockage of the nerve roots with anesthetic plus steroids. In a later separate procedure, the surgeon performs brief low-temperature radiofrequency rhizolysis.

Dr. Johnston presented a retrospective series of 10 patients with the distinctive, burning electricaltype pain of occipital neuralgia, 6 of whom also had migraine. The patients with migraine experienced orbital or periorbital pain referral upon direct stimulation at the C-1 level; those without migraine did not.

Nine of 10 patients had a positive nerve block, with either transient or sustained pain relief. The seven patients who didn’t experience sustained pain relief as a result of C-1, -2, and -3 nerve blockade subsequently underwent brief low-temperature radiofrequency rhizolysis. Four of the seven responded with a greater than 50% reduction in pain, headache days, and need for rescue medications; their responses lasted for an average of 5.5 months. The other three patients had a lesser response or no response.

No side effects or complications occurred as a consequence of the procedure. Future controlled studies are planned.

Dr. Johnston reported having no relevant financial disclosures.

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

"We don’t know that two doses would be as good as three for the duration of a woman’s life or a man’s life, but it may be good enough. You really want to protect people when they’re most sexually active and most likely to have multiple partners. Then when they settle down, they’re less likely to be at risk, and it doesn’t matter as much if they’re not as protected," Dr. Levin explained.

He reported that he serves as a consultant to Merck and GlaxoSmithKline and holds intellectual property rights involving Merck’s Zostavax shingles vaccine.

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

"We don’t know that two doses would be as good as three for the duration of a woman’s life or a man’s life, but it may be good enough. You really want to protect people when they’re most sexually active and most likely to have multiple partners. Then when they settle down, they’re less likely to be at risk, and it doesn’t matter as much if they’re not as protected," Dr. Levin explained.

He reported that he serves as a consultant to Merck and GlaxoSmithKline and holds intellectual property rights involving Merck’s Zostavax shingles vaccine.

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

"We don’t know that two doses would be as good as three for the duration of a woman’s life or a man’s life, but it may be good enough. You really want to protect people when they’re most sexually active and most likely to have multiple partners. Then when they settle down, they’re less likely to be at risk, and it doesn’t matter as much if they’re not as protected," Dr. Levin explained.

He reported that he serves as a consultant to Merck and GlaxoSmithKline and holds intellectual property rights involving Merck’s Zostavax shingles vaccine.

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

VAIL, COLO. – Expedited partner therapy is a novel approach to the treatment of sexually transmitted infections that’s catching on across much of the United States.

In expedited partner therapy, the physician treats the sexual partners of a patient diagnosed with chlamydia or gonorrhea by providing prescriptions or actual medications for the patient to pass along to his or her partners without prior examination of the partners by the health care provider.

"It’s a new concept that sometimes makes people uncomfortable. You have no relationship with the patient’s partners. But when you think about it from the public health perspective, you’re treating the sexual partners – and you may be preventing your patient from being reinfected," Dr. Ann-Christine Nyquist said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Ideally, the patient’s partner or partners should come in for a complete sexually transmitted disease (STD) evaluation and counseling plus treatment, but many times it’s just not possible to get them into care, said Dr. Nyquist, professor of pediatrics and associate dean at the University of Colorado, Denver.

Experts in the Division of STD Prevention at the Centers for Disease Control and Prevention are enthusiastic about expedited partner therapy. They see it as a way to put a dent in the estimated 3 million new cases of chlamydia and 700,000 of gonorrhea per year in the United States. Together with legal scholars at the Arizona State University College of Law in Tempe, the CDC has created a "Legal/Policy Toolkit for Adoption and Implementation of Expedited Partner Therapy."

The toolkit provides model legislation for consideration by state lawmakers. It also includes answers to frequently asked questions from physicians and pharmacists regarding issues such as prescription labeling requirements, breach of confidentiality considerations, and how the HIPAA Privacy Rule bears on expedited partner therapy.

At present, expedited partner therapy is permissible in 32 states, potentially allowable in 11, and prohibited in 7: Arkansas, Florida, Kentucky, Michigan, Ohio, Oklahoma, and West Virginia.

"You need to find out what the legal landscape is in your state," Dr. Nyquist advised.

She reported having no financial conflicts of interest.

VAIL, COLO. – Expedited partner therapy is a novel approach to the treatment of sexually transmitted infections that’s catching on across much of the United States.

In expedited partner therapy, the physician treats the sexual partners of a patient diagnosed with chlamydia or gonorrhea by providing prescriptions or actual medications for the patient to pass along to his or her partners without prior examination of the partners by the health care provider.

"It’s a new concept that sometimes makes people uncomfortable. You have no relationship with the patient’s partners. But when you think about it from the public health perspective, you’re treating the sexual partners – and you may be preventing your patient from being reinfected," Dr. Ann-Christine Nyquist said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Ideally, the patient’s partner or partners should come in for a complete sexually transmitted disease (STD) evaluation and counseling plus treatment, but many times it’s just not possible to get them into care, said Dr. Nyquist, professor of pediatrics and associate dean at the University of Colorado, Denver.

Experts in the Division of STD Prevention at the Centers for Disease Control and Prevention are enthusiastic about expedited partner therapy. They see it as a way to put a dent in the estimated 3 million new cases of chlamydia and 700,000 of gonorrhea per year in the United States. Together with legal scholars at the Arizona State University College of Law in Tempe, the CDC has created a "Legal/Policy Toolkit for Adoption and Implementation of Expedited Partner Therapy."

The toolkit provides model legislation for consideration by state lawmakers. It also includes answers to frequently asked questions from physicians and pharmacists regarding issues such as prescription labeling requirements, breach of confidentiality considerations, and how the HIPAA Privacy Rule bears on expedited partner therapy.

At present, expedited partner therapy is permissible in 32 states, potentially allowable in 11, and prohibited in 7: Arkansas, Florida, Kentucky, Michigan, Ohio, Oklahoma, and West Virginia.

"You need to find out what the legal landscape is in your state," Dr. Nyquist advised.

She reported having no financial conflicts of interest.

VAIL, COLO. – Expedited partner therapy is a novel approach to the treatment of sexually transmitted infections that’s catching on across much of the United States.

In expedited partner therapy, the physician treats the sexual partners of a patient diagnosed with chlamydia or gonorrhea by providing prescriptions or actual medications for the patient to pass along to his or her partners without prior examination of the partners by the health care provider.

"It’s a new concept that sometimes makes people uncomfortable. You have no relationship with the patient’s partners. But when you think about it from the public health perspective, you’re treating the sexual partners – and you may be preventing your patient from being reinfected," Dr. Ann-Christine Nyquist said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.

Ideally, the patient’s partner or partners should come in for a complete sexually transmitted disease (STD) evaluation and counseling plus treatment, but many times it’s just not possible to get them into care, said Dr. Nyquist, professor of pediatrics and associate dean at the University of Colorado, Denver.

Experts in the Division of STD Prevention at the Centers for Disease Control and Prevention are enthusiastic about expedited partner therapy. They see it as a way to put a dent in the estimated 3 million new cases of chlamydia and 700,000 of gonorrhea per year in the United States. Together with legal scholars at the Arizona State University College of Law in Tempe, the CDC has created a "Legal/Policy Toolkit for Adoption and Implementation of Expedited Partner Therapy."

The toolkit provides model legislation for consideration by state lawmakers. It also includes answers to frequently asked questions from physicians and pharmacists regarding issues such as prescription labeling requirements, breach of confidentiality considerations, and how the HIPAA Privacy Rule bears on expedited partner therapy.

At present, expedited partner therapy is permissible in 32 states, potentially allowable in 11, and prohibited in 7: Arkansas, Florida, Kentucky, Michigan, Ohio, Oklahoma, and West Virginia.

"You need to find out what the legal landscape is in your state," Dr. Nyquist advised.

She reported having no financial conflicts of interest.

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

©2008 Elsevier Ltd. All rights reserved.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

©2008 Elsevier Ltd. All rights reserved.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

©2008 Elsevier Ltd. All rights reserved.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.

VAIL, COLO. – A major theme running through the latest guidelines for management of community-acquired pneumonia in children is that Streptococcus pneumoniae is the most common bacterial pathogen – and the best target for empiric therapy.

"It’s really all about pneumococcus," declared Dr. Mark J. Abzug, professor of pediatrics at the University of Colorado, Denver.

The guidelines put forth jointly by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America endorse high-dose amoxicillin as first-line therapy for previously healthy, appropriately immunized infants, preschoolers, school-aged children, and adolescents with mild to moderate community-acquired pneumonia (CAP) of suspected bacterial origin (Clin. Infect. Dis. 2011; 53: e25-76).

High-dose oral amoxicillin at 90 mg/kg per day covers 87%-95% of S. pneumoniae isolates nationally, whereas most second- and third-generation oral cephalosporins cover only 60%-70%. Azithromycin isn’t recommended for suspected pneumococcal CAP because of an associated resistance rate of up to 40%. Amoxicillin/clavulanic acid offers no incremental benefit over amoxicillin alone for pneumococcus, Dr. Abzug observed at the conference, which was sponsored by Children’s Hospital Colorado.

The guidelines recommend b.i.d. dosing of amoxicillin based largely on extrapolation from experience in acute otitis media. But Dr. Abzug takes issue with that guidance.

"I’m going to beg to differ with that recommendation and suggest that for pneumonia, which is a bit different from otitis, dividing t.i.d. is going to be better," the pediatrician asserted.

Modeling studies indicate b.i.d. dosing of amoxicillin at 90 mg/kg per day is effective for 99% of highly susceptible (minimal inhibitory concentration of 0.5 mcg/mL) S. pneumococcus isolates, but only for 65% of strains with a minimum inhibitory concentration (MIC) of 2 mcg/mL, whereas t.i.d. dosing is sufficient for 90% of such strains. And at Children’s Hospital Colorado, nearly 20% of S. pneumoniae isolates in 2011 were intermediately susceptible (MIC = 4 mcg/mL) or resistant (MIC = 8 mcg/mL) to penicillin.

"For the 20% or so that are intermediate or resistant, b.i.d. dosing is not going to be the answer," Dr. Abzug stressed.

For patients with nonserious amoxicillin allergies, the guidelines recommend cefuroxime, cefprozil, or cefpodoxime as oral alternatives; nationally, 67%-80% of S. pneumoniae strains are susceptible to these agents. Clindamycin is an alternative option. Levofloxacin and linezolid are effective for close to 100% of isolates, but are best reserved for second- or third-line therapy.

It may come as a surprise to many physicians that the guidelines deem routine chest x-rays "not necessary" for suspected CAP in the outpatient setting.

"Will this encourage antibiotic overuse? The guidelines don’t address this," the pediatrician noted.

The guidelines also recommend against routine complete blood counts, blood cultures, and urinary antigen detection tests in outpatients.

In fully immunized children with suspected bacterial CAP sufficiently serious for hospitalization, the recommendation is for parenteral ampicillin or penicillin G so long as local epidemiologic data indicate a lack of substantial resistance for invasive pneumococci as defined by an MIC greater than 8 mcg/mL and the patient doesn’t have empyema or other potentially life-threatening complications. When those conditions aren’t met, however, the guidelines endorse the third-generation cephalosporins ceftriaxone or cefotaxime.

Dr. Abzug applauded a recent study by pediatricians at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., that provided support in everyday clinical practice for the ampicillin-first management strategy recommended in the national guidelines. The retrospective study included 1,033 patients admitted with CAP to the tertiary referral hospital during the 12 months before and after the 2008 introduction of a clinical practice guideline encouraging the use of ampicillin as the first-line empiric antibiotic in previously healthy children with uncomplicated CAP.

The Kansas City pediatricians noted that the use of ampicillin as first-line therapy has historically been uncommon at tertiary children’s hospitals, as evidenced by a mere 5.5% rate in a study using the Pediatric Hospital Information Systems database (Pediatrics 2011;127:e255-63). The goal was to turn that situation around at Children’s Mercy Hospitals and Clinics, since ampicillin is a narrower-spectrum antibiotic than the third-generation cephalosporins, and hence less likely to promote antibiotic resistance.

Prior to introduction of the hospital guideline, ceftriaxone was prescribed as empiric therapy for CAP in 72% of cases, with ampicillin being the second most commonly prescribed antibiotic at 13%. In the year after the guideline was introduced, ampicillin was the most common antibiotic, prescribed in 63% of cases, with ceftriaxone prescribed in 21%. And even though the prevalence of S. pneumoniae isolates with intermediate susceptibility or resistance to penicillin was 24% at the hospital during that time period, the change in therapy didn’t result in an increase in adverse outcomes: The preguideline treatment failure rate was 1.5% and the postguideline rate was similar at 1% (Pediatrics 2012;129:e597-604).

"Here’s some real-world data that suggest ampicillin for the most part is probably sufficient as the parenteral empiric drug of choice for uncomplicated CAP," Dr. Abzug commented.

Dr. Abzug reported having no financial conflicts.

VAIL, COLO. – A major theme running through the latest guidelines for management of community-acquired pneumonia in children is that Streptococcus pneumoniae is the most common bacterial pathogen – and the best target for empiric therapy.

"It’s really all about pneumococcus," declared Dr. Mark J. Abzug, professor of pediatrics at the University of Colorado, Denver.

The guidelines put forth jointly by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America endorse high-dose amoxicillin as first-line therapy for previously healthy, appropriately immunized infants, preschoolers, school-aged children, and adolescents with mild to moderate community-acquired pneumonia (CAP) of suspected bacterial origin (Clin. Infect. Dis. 2011; 53: e25-76).

High-dose oral amoxicillin at 90 mg/kg per day covers 87%-95% of S. pneumoniae isolates nationally, whereas most second- and third-generation oral cephalosporins cover only 60%-70%. Azithromycin isn’t recommended for suspected pneumococcal CAP because of an associated resistance rate of up to 40%. Amoxicillin/clavulanic acid offers no incremental benefit over amoxicillin alone for pneumococcus, Dr. Abzug observed at the conference, which was sponsored by Children’s Hospital Colorado.

The guidelines recommend b.i.d. dosing of amoxicillin based largely on extrapolation from experience in acute otitis media. But Dr. Abzug takes issue with that guidance.

"I’m going to beg to differ with that recommendation and suggest that for pneumonia, which is a bit different from otitis, dividing t.i.d. is going to be better," the pediatrician asserted.

Modeling studies indicate b.i.d. dosing of amoxicillin at 90 mg/kg per day is effective for 99% of highly susceptible (minimal inhibitory concentration of 0.5 mcg/mL) S. pneumococcus isolates, but only for 65% of strains with a minimum inhibitory concentration (MIC) of 2 mcg/mL, whereas t.i.d. dosing is sufficient for 90% of such strains. And at Children’s Hospital Colorado, nearly 20% of S. pneumoniae isolates in 2011 were intermediately susceptible (MIC = 4 mcg/mL) or resistant (MIC = 8 mcg/mL) to penicillin.

"For the 20% or so that are intermediate or resistant, b.i.d. dosing is not going to be the answer," Dr. Abzug stressed.

For patients with nonserious amoxicillin allergies, the guidelines recommend cefuroxime, cefprozil, or cefpodoxime as oral alternatives; nationally, 67%-80% of S. pneumoniae strains are susceptible to these agents. Clindamycin is an alternative option. Levofloxacin and linezolid are effective for close to 100% of isolates, but are best reserved for second- or third-line therapy.

It may come as a surprise to many physicians that the guidelines deem routine chest x-rays "not necessary" for suspected CAP in the outpatient setting.

"Will this encourage antibiotic overuse? The guidelines don’t address this," the pediatrician noted.

The guidelines also recommend against routine complete blood counts, blood cultures, and urinary antigen detection tests in outpatients.

In fully immunized children with suspected bacterial CAP sufficiently serious for hospitalization, the recommendation is for parenteral ampicillin or penicillin G so long as local epidemiologic data indicate a lack of substantial resistance for invasive pneumococci as defined by an MIC greater than 8 mcg/mL and the patient doesn’t have empyema or other potentially life-threatening complications. When those conditions aren’t met, however, the guidelines endorse the third-generation cephalosporins ceftriaxone or cefotaxime.

Dr. Abzug applauded a recent study by pediatricians at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., that provided support in everyday clinical practice for the ampicillin-first management strategy recommended in the national guidelines. The retrospective study included 1,033 patients admitted with CAP to the tertiary referral hospital during the 12 months before and after the 2008 introduction of a clinical practice guideline encouraging the use of ampicillin as the first-line empiric antibiotic in previously healthy children with uncomplicated CAP.

The Kansas City pediatricians noted that the use of ampicillin as first-line therapy has historically been uncommon at tertiary children’s hospitals, as evidenced by a mere 5.5% rate in a study using the Pediatric Hospital Information Systems database (Pediatrics 2011;127:e255-63). The goal was to turn that situation around at Children’s Mercy Hospitals and Clinics, since ampicillin is a narrower-spectrum antibiotic than the third-generation cephalosporins, and hence less likely to promote antibiotic resistance.

Prior to introduction of the hospital guideline, ceftriaxone was prescribed as empiric therapy for CAP in 72% of cases, with ampicillin being the second most commonly prescribed antibiotic at 13%. In the year after the guideline was introduced, ampicillin was the most common antibiotic, prescribed in 63% of cases, with ceftriaxone prescribed in 21%. And even though the prevalence of S. pneumoniae isolates with intermediate susceptibility or resistance to penicillin was 24% at the hospital during that time period, the change in therapy didn’t result in an increase in adverse outcomes: The preguideline treatment failure rate was 1.5% and the postguideline rate was similar at 1% (Pediatrics 2012;129:e597-604).

"Here’s some real-world data that suggest ampicillin for the most part is probably sufficient as the parenteral empiric drug of choice for uncomplicated CAP," Dr. Abzug commented.

Dr. Abzug reported having no financial conflicts.

VAIL, COLO. – A major theme running through the latest guidelines for management of community-acquired pneumonia in children is that Streptococcus pneumoniae is the most common bacterial pathogen – and the best target for empiric therapy.

"It’s really all about pneumococcus," declared Dr. Mark J. Abzug, professor of pediatrics at the University of Colorado, Denver.

The guidelines put forth jointly by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America endorse high-dose amoxicillin as first-line therapy for previously healthy, appropriately immunized infants, preschoolers, school-aged children, and adolescents with mild to moderate community-acquired pneumonia (CAP) of suspected bacterial origin (Clin. Infect. Dis. 2011; 53: e25-76).

High-dose oral amoxicillin at 90 mg/kg per day covers 87%-95% of S. pneumoniae isolates nationally, whereas most second- and third-generation oral cephalosporins cover only 60%-70%. Azithromycin isn’t recommended for suspected pneumococcal CAP because of an associated resistance rate of up to 40%. Amoxicillin/clavulanic acid offers no incremental benefit over amoxicillin alone for pneumococcus, Dr. Abzug observed at the conference, which was sponsored by Children’s Hospital Colorado.

The guidelines recommend b.i.d. dosing of amoxicillin based largely on extrapolation from experience in acute otitis media. But Dr. Abzug takes issue with that guidance.

"I’m going to beg to differ with that recommendation and suggest that for pneumonia, which is a bit different from otitis, dividing t.i.d. is going to be better," the pediatrician asserted.

Modeling studies indicate b.i.d. dosing of amoxicillin at 90 mg/kg per day is effective for 99% of highly susceptible (minimal inhibitory concentration of 0.5 mcg/mL) S. pneumococcus isolates, but only for 65% of strains with a minimum inhibitory concentration (MIC) of 2 mcg/mL, whereas t.i.d. dosing is sufficient for 90% of such strains. And at Children’s Hospital Colorado, nearly 20% of S. pneumoniae isolates in 2011 were intermediately susceptible (MIC = 4 mcg/mL) or resistant (MIC = 8 mcg/mL) to penicillin.

"For the 20% or so that are intermediate or resistant, b.i.d. dosing is not going to be the answer," Dr. Abzug stressed.

For patients with nonserious amoxicillin allergies, the guidelines recommend cefuroxime, cefprozil, or cefpodoxime as oral alternatives; nationally, 67%-80% of S. pneumoniae strains are susceptible to these agents. Clindamycin is an alternative option. Levofloxacin and linezolid are effective for close to 100% of isolates, but are best reserved for second- or third-line therapy.

It may come as a surprise to many physicians that the guidelines deem routine chest x-rays "not necessary" for suspected CAP in the outpatient setting.

"Will this encourage antibiotic overuse? The guidelines don’t address this," the pediatrician noted.

The guidelines also recommend against routine complete blood counts, blood cultures, and urinary antigen detection tests in outpatients.

In fully immunized children with suspected bacterial CAP sufficiently serious for hospitalization, the recommendation is for parenteral ampicillin or penicillin G so long as local epidemiologic data indicate a lack of substantial resistance for invasive pneumococci as defined by an MIC greater than 8 mcg/mL and the patient doesn’t have empyema or other potentially life-threatening complications. When those conditions aren’t met, however, the guidelines endorse the third-generation cephalosporins ceftriaxone or cefotaxime.

Dr. Abzug applauded a recent study by pediatricians at Children’s Mercy Hospitals and Clinics in Kansas City, Mo., that provided support in everyday clinical practice for the ampicillin-first management strategy recommended in the national guidelines. The retrospective study included 1,033 patients admitted with CAP to the tertiary referral hospital during the 12 months before and after the 2008 introduction of a clinical practice guideline encouraging the use of ampicillin as the first-line empiric antibiotic in previously healthy children with uncomplicated CAP.

The Kansas City pediatricians noted that the use of ampicillin as first-line therapy has historically been uncommon at tertiary children’s hospitals, as evidenced by a mere 5.5% rate in a study using the Pediatric Hospital Information Systems database (Pediatrics 2011;127:e255-63). The goal was to turn that situation around at Children’s Mercy Hospitals and Clinics, since ampicillin is a narrower-spectrum antibiotic than the third-generation cephalosporins, and hence less likely to promote antibiotic resistance.

Prior to introduction of the hospital guideline, ceftriaxone was prescribed as empiric therapy for CAP in 72% of cases, with ampicillin being the second most commonly prescribed antibiotic at 13%. In the year after the guideline was introduced, ampicillin was the most common antibiotic, prescribed in 63% of cases, with ceftriaxone prescribed in 21%. And even though the prevalence of S. pneumoniae isolates with intermediate susceptibility or resistance to penicillin was 24% at the hospital during that time period, the change in therapy didn’t result in an increase in adverse outcomes: The preguideline treatment failure rate was 1.5% and the postguideline rate was similar at 1% (Pediatrics 2012;129:e597-604).

"Here’s some real-world data that suggest ampicillin for the most part is probably sufficient as the parenteral empiric drug of choice for uncomplicated CAP," Dr. Abzug commented.

Dr. Abzug reported having no financial conflicts.

ESTES PARK, COLO. – Topping Dr. Jeffrey I. Wallace’s pantheon of peeves in prescribing for the elderly are:

• Megestrol acetate (Megace): These are widely prescribed in older patients who aren’t eating well and are experiencing failure to thrive. But the randomized trials with 6- to 12-month followup clearly show that any modest benefit achieved in terms of weight gain takes 2-3 months of therapy. And megestrol acetate is a progestational agent associated with increased risk of thrombotic events and a possible increase in mortality.

"The data on Megace really look terrible. I much prefer using mirtazapine to increase appetite in a patient with even a hint of depression. I’d probably use medical marijuana in the form of Marinol [dronabinol] before I’d use Megace," declared Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

• Oral iron more than once daily: "I see patients in the nursing homes all the time who’ve been discharged from the hospital by the surgeons on T.I.D. (three times a day) iron," according to the geriatrician.

Absorption of iron is an active process occurring in the duodenum and jejunum. By taking once-daily iron, a patient gets roughly 75% of all the iron that can possibly be absorbed in a day. Moving up to B.I.D. iron, that figure rises to 90%, and T.I.D. dosing bumps up another 5%.

"So each time, I get a little more iron absorbed. The problem is I get a lot more GI side effects. Most of the geriatric patients I see after they get out of the hospital aren’t feeling good already – and now I’m going to make them constipated and give them some dyspepsia and decreased appetite? It’s just not worth it; you don’t get much more bang for the buck. I’m pretty much a stickler to always take the iron down to once a day," he said.

A tip: Oral iron requires an acid environment to be absorbed well. A patient who has had a GI bleed or is at increased risk because of chronic NSAID therapy is likely to be on a proton pump inhibitor, which will interfere with iron absorption. "Have the patient take the iron with some orange juice or vitamin C to help absorption. The data isn’t all that good that it makes much difference, but it’s worth a try," according to the geriatrician.

• Muscle relaxants: These medications are sedating; cause anticholinergic side effects and are linked to an increased risk of falls; and are of questionable efficacy.

"It used to be that if you were 65 or 70 [years old] and came to the ED with back pain, everyone walked out of there with Flexeril [cyclobenzaprine] or some variant thereof. Our ED at the university pretty much doesn’t hand out muscle relaxants anymore. They’re not really pain pills; the data are terrible in terms of helping pain. For run-of-the-mill back pain, I’d rather give an older patient an opiate than a muscle relaxant. So unless you have a definitive muscle spasm, treat the pain with pain pills," he urged at the conference.

He reported having no financial conflicts.

ESTES PARK, COLO. – Topping Dr. Jeffrey I. Wallace’s pantheon of peeves in prescribing for the elderly are:

• Megestrol acetate (Megace): These are widely prescribed in older patients who aren’t eating well and are experiencing failure to thrive. But the randomized trials with 6- to 12-month followup clearly show that any modest benefit achieved in terms of weight gain takes 2-3 months of therapy. And megestrol acetate is a progestational agent associated with increased risk of thrombotic events and a possible increase in mortality.

"The data on Megace really look terrible. I much prefer using mirtazapine to increase appetite in a patient with even a hint of depression. I’d probably use medical marijuana in the form of Marinol [dronabinol] before I’d use Megace," declared Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

• Oral iron more than once daily: "I see patients in the nursing homes all the time who’ve been discharged from the hospital by the surgeons on T.I.D. (three times a day) iron," according to the geriatrician.

Absorption of iron is an active process occurring in the duodenum and jejunum. By taking once-daily iron, a patient gets roughly 75% of all the iron that can possibly be absorbed in a day. Moving up to B.I.D. iron, that figure rises to 90%, and T.I.D. dosing bumps up another 5%.

"So each time, I get a little more iron absorbed. The problem is I get a lot more GI side effects. Most of the geriatric patients I see after they get out of the hospital aren’t feeling good already – and now I’m going to make them constipated and give them some dyspepsia and decreased appetite? It’s just not worth it; you don’t get much more bang for the buck. I’m pretty much a stickler to always take the iron down to once a day," he said.

A tip: Oral iron requires an acid environment to be absorbed well. A patient who has had a GI bleed or is at increased risk because of chronic NSAID therapy is likely to be on a proton pump inhibitor, which will interfere with iron absorption. "Have the patient take the iron with some orange juice or vitamin C to help absorption. The data isn’t all that good that it makes much difference, but it’s worth a try," according to the geriatrician.

• Muscle relaxants: These medications are sedating; cause anticholinergic side effects and are linked to an increased risk of falls; and are of questionable efficacy.

"It used to be that if you were 65 or 70 [years old] and came to the ED with back pain, everyone walked out of there with Flexeril [cyclobenzaprine] or some variant thereof. Our ED at the university pretty much doesn’t hand out muscle relaxants anymore. They’re not really pain pills; the data are terrible in terms of helping pain. For run-of-the-mill back pain, I’d rather give an older patient an opiate than a muscle relaxant. So unless you have a definitive muscle spasm, treat the pain with pain pills," he urged at the conference.

He reported having no financial conflicts.

ESTES PARK, COLO. – Topping Dr. Jeffrey I. Wallace’s pantheon of peeves in prescribing for the elderly are:

• Megestrol acetate (Megace): These are widely prescribed in older patients who aren’t eating well and are experiencing failure to thrive. But the randomized trials with 6- to 12-month followup clearly show that any modest benefit achieved in terms of weight gain takes 2-3 months of therapy. And megestrol acetate is a progestational agent associated with increased risk of thrombotic events and a possible increase in mortality.

"The data on Megace really look terrible. I much prefer using mirtazapine to increase appetite in a patient with even a hint of depression. I’d probably use medical marijuana in the form of Marinol [dronabinol] before I’d use Megace," declared Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

• Oral iron more than once daily: "I see patients in the nursing homes all the time who’ve been discharged from the hospital by the surgeons on T.I.D. (three times a day) iron," according to the geriatrician.

Absorption of iron is an active process occurring in the duodenum and jejunum. By taking once-daily iron, a patient gets roughly 75% of all the iron that can possibly be absorbed in a day. Moving up to B.I.D. iron, that figure rises to 90%, and T.I.D. dosing bumps up another 5%.

"So each time, I get a little more iron absorbed. The problem is I get a lot more GI side effects. Most of the geriatric patients I see after they get out of the hospital aren’t feeling good already – and now I’m going to make them constipated and give them some dyspepsia and decreased appetite? It’s just not worth it; you don’t get much more bang for the buck. I’m pretty much a stickler to always take the iron down to once a day," he said.

A tip: Oral iron requires an acid environment to be absorbed well. A patient who has had a GI bleed or is at increased risk because of chronic NSAID therapy is likely to be on a proton pump inhibitor, which will interfere with iron absorption. "Have the patient take the iron with some orange juice or vitamin C to help absorption. The data isn’t all that good that it makes much difference, but it’s worth a try," according to the geriatrician.

• Muscle relaxants: These medications are sedating; cause anticholinergic side effects and are linked to an increased risk of falls; and are of questionable efficacy.

"It used to be that if you were 65 or 70 [years old] and came to the ED with back pain, everyone walked out of there with Flexeril [cyclobenzaprine] or some variant thereof. Our ED at the university pretty much doesn’t hand out muscle relaxants anymore. They’re not really pain pills; the data are terrible in terms of helping pain. For run-of-the-mill back pain, I’d rather give an older patient an opiate than a muscle relaxant. So unless you have a definitive muscle spasm, treat the pain with pain pills," he urged at the conference.

He reported having no financial conflicts.