Sherry Boschert

SAN FRANCISCO — All infants should be screened for anemia around 12 months of age by measuring hemoglobin concentrations and assessing risk factors associated with iron deficiency or iron-deficiency anemia, a new clinical report advises.

If the hemoglobin level is less than 11 g/dL, or if the infant has a high risk of dietary iron deficiency, physicians should test further by measuring serum ferritin and C-reactive protein (CRP) or by measuring reticulocyte hemoglobin concentration (CHr), according to the report.

These recommendations for screening are controversial, Dr. Frank Greer, a co-author of the report on iron deficiency and iron-deficiency anemia, said at the meeting.

"It's going to be very burdensome to screen for iron deficiency. It's burdensome until we get some kind of a spot test," said Dr. Greer, professor of pediatrics at the University of Wisconsin, Madison. "But until somebody makes a hue and cry that we need to screen kids for iron deficiency, the technology won't come around. Hopefully, this will stimulate the technology."

It's unclear who will pay the added cost involved in screening. About 55% of U.S. children would fit criteria for the need to screen with more than just a hemoglobin test simply because of their low socioeconomic status, which is a key risk factor for dietary iron deficiency, he noted. Other risk factors outlined in the report include a history of prematurity or low birth weight, exposure to lead, exclusive breast feeding beyond 4 months of age without supplemental iron, feeding problems, and poor growth.

The "Clinical Report – Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in Infants and Young Children (0–3 Years of Age)" will be published in the November issue of the journal Pediatrics. Dr. Greer was the lead co-author of the report with Dr. Robert D. Baker, professor of pediatrics at the State University of New York, Buffalo and Women's and Children's Hospital, Buffalo. The AAP's Committee on Nutrition also contributed to the report.

The new report revises and expands on a 1999 AAP policy statement that focused on iron fortification of formulas (Pediatrics 1999;104:119–23).

Serum ferritin concentration is the most widely available measure of total body iron stores, but concentrations of serum ferritin may be increased by infection (inflammation), malignancy, liver disease, or anemia of chronic disease. If used to diagnose iron deficiency, serum ferritin concentration must be combined with simultaneous measurement of CRP to rule out inflammation. If the CRP is elevated, one of the other recommended tests must be used to screen for iron deficiency, Dr. Greer explained.

The standard for diagnosing iron deficiency is low bone marrow iron concentration determined by iron staining – not a practical choice for clinicians. Three other parameters provide the most discriminatory information about iron status: serum ferritin, CHr, or transferrin receptor 1 concentration (TfR1), Dr. Greer said. CHr and TfR1 are not affected by inflammation, malignancy, or anemia of chronic disease. Serum TfR1 assays are not widely available and are not standardized for use in infants and children. The CHr assay is measured by flow cytometry, but only two of the four commonly used automated analyzers in the United States are able to measure CHr.

"Hopefully, within a generation they all will" measure CHr, he said.

The statement offers an alternative way to diagnose iron-deficiency anemia that was one of the compromises made among the authors, Dr. Greer said. A child with mild anemia (a hemoglobin level of 10–11 g/dL) and a history suggesting an iron-deficient diet could be given iron replacement therapy, and if the plasma hemoglobin concentration increases by 1 g/dL after 1 month, would be considered to have had iron deficiency.

Any child with iron deficiency or iron-deficiency anemia should be followed carefully, he added.

The statement also recommended steps to prevent iron deficiency and iron-deficiency anemia, including the option of iron supplements. Term healthy infants have sufficient iron for the first 4 months of life. Starting at 4 months, breast-fed infants should be given 1 mg/kg a day of oral iron supplementation until iron-rich complementary foods are introduced, the statement says. Exclusively formula-fed infants get adequate iron from formula. Whole milk should not be used before 12 months of age. At 6–12 months of age, infants need 11 mg/kg a day of iron. Red meat and vegetables with high iron content should be introduced early when complementary foods are given, and liquid iron supplements can be used if diet and formula do not provide enough iron.

Toddlers aged 1–3 years need 7 mg/day of iron, which is best obtained from foods but can be had from liquid iron supplements and chewable vitamins if needed.

All preterm infants should get at least 2 mg/kg a day of iron (the amount in iron-fortified formulas) through 12 months of age. Preterm infants feeding on human milk should get an iron supplement of 2 mg/kg a day by 1 month of age, which should be continued until the infant is weaned to iron-fortified formula or begins eating complementary foods that provide 2 mg/kg a day of iron.

Try mixing iron supplements with food or formula to make it more palatable, Dr. Greer suggested. "It tastes nasty" and can stain clothing if the baby spits it up, he said. Tri-Vi-Sol, which contains vitamins A, C, and D with iron, can be used. Giving iron starting at birth is not recommended. Alternatively, give the child some red meat in baby food or other forms. In Germany, often the first food introduced to children is a mash of vegetables, potatoes, and red meat.

The screening recommendations are the most controversial, but the prevention recommendations also are not without controversy. Iron is "both a good guy and a bad guy – either too much or too little are bad for you," and the difference between the lower and upper limits of intake are very narrow, compared with most other nutrients, Dr. Greer explained. Many physicians are unwilling to give iron supplements or iron-rich foods to children younger than 6 months or even to older children, he noted.

About 4% of 6-month-old infants and 12% of 12-month-olds in the United States are iron deficient. In toddlers aged 1–3 years, iron deficiency occurs in 7%-15%, depending on ethnicity and socioeconomic status.

Data from the 1999–2002 National Health and Nutrition Examination Survey (NHANES) suggest that 9% of children aged 12–35 months are iron deficient and 2% have iron-deficiency anemia. These data drove the AAP to create the new report, Dr. Greer said.

"I've worked on a lot of statements. This was by far the most difficult and controversial," he added.

The report declared that the authors had no pertinent conflicts of interest.

SAN FRANCISCO — All infants should be screened for anemia around 12 months of age by measuring hemoglobin concentrations and assessing risk factors associated with iron deficiency or iron-deficiency anemia, a new clinical report advises.

If the hemoglobin level is less than 11 g/dL, or if the infant has a high risk of dietary iron deficiency, physicians should test further by measuring serum ferritin and C-reactive protein (CRP) or by measuring reticulocyte hemoglobin concentration (CHr), according to the report.

These recommendations for screening are controversial, Dr. Frank Greer, a co-author of the report on iron deficiency and iron-deficiency anemia, said at the meeting.

"It's going to be very burdensome to screen for iron deficiency. It's burdensome until we get some kind of a spot test," said Dr. Greer, professor of pediatrics at the University of Wisconsin, Madison. "But until somebody makes a hue and cry that we need to screen kids for iron deficiency, the technology won't come around. Hopefully, this will stimulate the technology."

It's unclear who will pay the added cost involved in screening. About 55% of U.S. children would fit criteria for the need to screen with more than just a hemoglobin test simply because of their low socioeconomic status, which is a key risk factor for dietary iron deficiency, he noted. Other risk factors outlined in the report include a history of prematurity or low birth weight, exposure to lead, exclusive breast feeding beyond 4 months of age without supplemental iron, feeding problems, and poor growth.

The "Clinical Report – Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in Infants and Young Children (0–3 Years of Age)" will be published in the November issue of the journal Pediatrics. Dr. Greer was the lead co-author of the report with Dr. Robert D. Baker, professor of pediatrics at the State University of New York, Buffalo and Women's and Children's Hospital, Buffalo. The AAP's Committee on Nutrition also contributed to the report.

The new report revises and expands on a 1999 AAP policy statement that focused on iron fortification of formulas (Pediatrics 1999;104:119–23).

Serum ferritin concentration is the most widely available measure of total body iron stores, but concentrations of serum ferritin may be increased by infection (inflammation), malignancy, liver disease, or anemia of chronic disease. If used to diagnose iron deficiency, serum ferritin concentration must be combined with simultaneous measurement of CRP to rule out inflammation. If the CRP is elevated, one of the other recommended tests must be used to screen for iron deficiency, Dr. Greer explained.

The standard for diagnosing iron deficiency is low bone marrow iron concentration determined by iron staining – not a practical choice for clinicians. Three other parameters provide the most discriminatory information about iron status: serum ferritin, CHr, or transferrin receptor 1 concentration (TfR1), Dr. Greer said. CHr and TfR1 are not affected by inflammation, malignancy, or anemia of chronic disease. Serum TfR1 assays are not widely available and are not standardized for use in infants and children. The CHr assay is measured by flow cytometry, but only two of the four commonly used automated analyzers in the United States are able to measure CHr.

"Hopefully, within a generation they all will" measure CHr, he said.

The statement offers an alternative way to diagnose iron-deficiency anemia that was one of the compromises made among the authors, Dr. Greer said. A child with mild anemia (a hemoglobin level of 10–11 g/dL) and a history suggesting an iron-deficient diet could be given iron replacement therapy, and if the plasma hemoglobin concentration increases by 1 g/dL after 1 month, would be considered to have had iron deficiency.

Any child with iron deficiency or iron-deficiency anemia should be followed carefully, he added.

The statement also recommended steps to prevent iron deficiency and iron-deficiency anemia, including the option of iron supplements. Term healthy infants have sufficient iron for the first 4 months of life. Starting at 4 months, breast-fed infants should be given 1 mg/kg a day of oral iron supplementation until iron-rich complementary foods are introduced, the statement says. Exclusively formula-fed infants get adequate iron from formula. Whole milk should not be used before 12 months of age. At 6–12 months of age, infants need 11 mg/kg a day of iron. Red meat and vegetables with high iron content should be introduced early when complementary foods are given, and liquid iron supplements can be used if diet and formula do not provide enough iron.

Toddlers aged 1–3 years need 7 mg/day of iron, which is best obtained from foods but can be had from liquid iron supplements and chewable vitamins if needed.

All preterm infants should get at least 2 mg/kg a day of iron (the amount in iron-fortified formulas) through 12 months of age. Preterm infants feeding on human milk should get an iron supplement of 2 mg/kg a day by 1 month of age, which should be continued until the infant is weaned to iron-fortified formula or begins eating complementary foods that provide 2 mg/kg a day of iron.

Try mixing iron supplements with food or formula to make it more palatable, Dr. Greer suggested. "It tastes nasty" and can stain clothing if the baby spits it up, he said. Tri-Vi-Sol, which contains vitamins A, C, and D with iron, can be used. Giving iron starting at birth is not recommended. Alternatively, give the child some red meat in baby food or other forms. In Germany, often the first food introduced to children is a mash of vegetables, potatoes, and red meat.

The screening recommendations are the most controversial, but the prevention recommendations also are not without controversy. Iron is "both a good guy and a bad guy – either too much or too little are bad for you," and the difference between the lower and upper limits of intake are very narrow, compared with most other nutrients, Dr. Greer explained. Many physicians are unwilling to give iron supplements or iron-rich foods to children younger than 6 months or even to older children, he noted.

About 4% of 6-month-old infants and 12% of 12-month-olds in the United States are iron deficient. In toddlers aged 1–3 years, iron deficiency occurs in 7%-15%, depending on ethnicity and socioeconomic status.

Data from the 1999–2002 National Health and Nutrition Examination Survey (NHANES) suggest that 9% of children aged 12–35 months are iron deficient and 2% have iron-deficiency anemia. These data drove the AAP to create the new report, Dr. Greer said.

"I've worked on a lot of statements. This was by far the most difficult and controversial," he added.

The report declared that the authors had no pertinent conflicts of interest.

SAN FRANCISCO — All infants should be screened for anemia around 12 months of age by measuring hemoglobin concentrations and assessing risk factors associated with iron deficiency or iron-deficiency anemia, a new clinical report advises.

If the hemoglobin level is less than 11 g/dL, or if the infant has a high risk of dietary iron deficiency, physicians should test further by measuring serum ferritin and C-reactive protein (CRP) or by measuring reticulocyte hemoglobin concentration (CHr), according to the report.

These recommendations for screening are controversial, Dr. Frank Greer, a co-author of the report on iron deficiency and iron-deficiency anemia, said at the meeting.

"It's going to be very burdensome to screen for iron deficiency. It's burdensome until we get some kind of a spot test," said Dr. Greer, professor of pediatrics at the University of Wisconsin, Madison. "But until somebody makes a hue and cry that we need to screen kids for iron deficiency, the technology won't come around. Hopefully, this will stimulate the technology."

It's unclear who will pay the added cost involved in screening. About 55% of U.S. children would fit criteria for the need to screen with more than just a hemoglobin test simply because of their low socioeconomic status, which is a key risk factor for dietary iron deficiency, he noted. Other risk factors outlined in the report include a history of prematurity or low birth weight, exposure to lead, exclusive breast feeding beyond 4 months of age without supplemental iron, feeding problems, and poor growth.

The "Clinical Report – Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in Infants and Young Children (0–3 Years of Age)" will be published in the November issue of the journal Pediatrics. Dr. Greer was the lead co-author of the report with Dr. Robert D. Baker, professor of pediatrics at the State University of New York, Buffalo and Women's and Children's Hospital, Buffalo. The AAP's Committee on Nutrition also contributed to the report.

The new report revises and expands on a 1999 AAP policy statement that focused on iron fortification of formulas (Pediatrics 1999;104:119–23).

Serum ferritin concentration is the most widely available measure of total body iron stores, but concentrations of serum ferritin may be increased by infection (inflammation), malignancy, liver disease, or anemia of chronic disease. If used to diagnose iron deficiency, serum ferritin concentration must be combined with simultaneous measurement of CRP to rule out inflammation. If the CRP is elevated, one of the other recommended tests must be used to screen for iron deficiency, Dr. Greer explained.

The standard for diagnosing iron deficiency is low bone marrow iron concentration determined by iron staining – not a practical choice for clinicians. Three other parameters provide the most discriminatory information about iron status: serum ferritin, CHr, or transferrin receptor 1 concentration (TfR1), Dr. Greer said. CHr and TfR1 are not affected by inflammation, malignancy, or anemia of chronic disease. Serum TfR1 assays are not widely available and are not standardized for use in infants and children. The CHr assay is measured by flow cytometry, but only two of the four commonly used automated analyzers in the United States are able to measure CHr.

"Hopefully, within a generation they all will" measure CHr, he said.

The statement offers an alternative way to diagnose iron-deficiency anemia that was one of the compromises made among the authors, Dr. Greer said. A child with mild anemia (a hemoglobin level of 10–11 g/dL) and a history suggesting an iron-deficient diet could be given iron replacement therapy, and if the plasma hemoglobin concentration increases by 1 g/dL after 1 month, would be considered to have had iron deficiency.

Any child with iron deficiency or iron-deficiency anemia should be followed carefully, he added.

The statement also recommended steps to prevent iron deficiency and iron-deficiency anemia, including the option of iron supplements. Term healthy infants have sufficient iron for the first 4 months of life. Starting at 4 months, breast-fed infants should be given 1 mg/kg a day of oral iron supplementation until iron-rich complementary foods are introduced, the statement says. Exclusively formula-fed infants get adequate iron from formula. Whole milk should not be used before 12 months of age. At 6–12 months of age, infants need 11 mg/kg a day of iron. Red meat and vegetables with high iron content should be introduced early when complementary foods are given, and liquid iron supplements can be used if diet and formula do not provide enough iron.

Toddlers aged 1–3 years need 7 mg/day of iron, which is best obtained from foods but can be had from liquid iron supplements and chewable vitamins if needed.

All preterm infants should get at least 2 mg/kg a day of iron (the amount in iron-fortified formulas) through 12 months of age. Preterm infants feeding on human milk should get an iron supplement of 2 mg/kg a day by 1 month of age, which should be continued until the infant is weaned to iron-fortified formula or begins eating complementary foods that provide 2 mg/kg a day of iron.

Try mixing iron supplements with food or formula to make it more palatable, Dr. Greer suggested. "It tastes nasty" and can stain clothing if the baby spits it up, he said. Tri-Vi-Sol, which contains vitamins A, C, and D with iron, can be used. Giving iron starting at birth is not recommended. Alternatively, give the child some red meat in baby food or other forms. In Germany, often the first food introduced to children is a mash of vegetables, potatoes, and red meat.

The screening recommendations are the most controversial, but the prevention recommendations also are not without controversy. Iron is "both a good guy and a bad guy – either too much or too little are bad for you," and the difference between the lower and upper limits of intake are very narrow, compared with most other nutrients, Dr. Greer explained. Many physicians are unwilling to give iron supplements or iron-rich foods to children younger than 6 months or even to older children, he noted.

About 4% of 6-month-old infants and 12% of 12-month-olds in the United States are iron deficient. In toddlers aged 1–3 years, iron deficiency occurs in 7%-15%, depending on ethnicity and socioeconomic status.

Data from the 1999–2002 National Health and Nutrition Examination Survey (NHANES) suggest that 9% of children aged 12–35 months are iron deficient and 2% have iron-deficiency anemia. These data drove the AAP to create the new report, Dr. Greer said.

"I've worked on a lot of statements. This was by far the most difficult and controversial," he added.

The report declared that the authors had no pertinent conflicts of interest.

PASADENA, CALIF. — Two drugs — one old, one new — are showing promise in early clinical trials for the treatment of basal cell carcinomas.

If they prove to be useful, clinicians can thank scientists who successfully identified abnormalities in the hedgehog signaling pathway as the mechanism of disease for basal cell carcinoma (BCC), Dr. Jean Tang said at the meeting.

“Every major pharmaceutical company is now interested in the hedgehog pathway, so we may see a lot of treatments in the near future” for BCC and other cancers, said Dr. Tang of Stanford (Calif.) University.

She and her associates are conducting a phase II trial of the experimental Genentech drug GDC-0449 in patients with many BCCs from basal cell nevus syndrome (Gorlin's syndrome), and a separate proof-of-concept study of the antifungal drug itraconazole in patients with small numbers of BCCs who do not have basal cell nevus syndrome.

For GDC-0449, a previous phase I study in 33 patients with locally advanced or metastatic BCC who took the drug for a median of 10 months found that 50%-60% had partial or complete responses and the drug was generally well tolerated (N. Engl. J. Med. 2009;361:1164–72).

Of the 41 patients with basal cell nevus syndrome recruited thus far for the phase II trial — and randomized to 18 months of treatment with GDC-0449 or placebo — 23 patients (with 953 BCC tumors) have more than 1 month of data.

Although the study is still blinded, 15 patients in group A have developed a median of one new BCC during that month, compared with a median of 10 new BCCs in each of the 8 patients in group B, a significant difference that suggests group A may have received the drug and it may be working, Dr. Tang suggested.

In group A, patients started with a median of 252 BCCs and had 127 at the most recent follow-up, a 50% decline. In group B, patients started with 217 BCCs and had 267 at follow-up, a 23% increase in BCCs.

The difference between groups is significant, she said. Existing BCCs in group A also seem to have decreased in size.

“In the patients who have responded, it has changed their lives,” Dr. Tang said. “We are really excited about it.”

Patients in group A, however, were significantly more likely to develop dysgeusia (decreased taste sensation). The condition was seen in 14 of 15 patients, compared with none in group B. Seven patients in group A and none in group B reported some hair loss, though this difference was not statistically significant. Two patients in group A stopped treatment because of dysgeusia and hair loss, compared with none in group B.

These side effects may be acceptable to patients with basal cell nevus syndrome but probably not to patients with only one or two BCCs, Dr. Tang noted.

For the latter group, a proof-of-concept trial has randomized eight patients thus far to 1 month of treatment with 400 mg/day of oral itraconazole, a drug that has been on the market for approximately 2 decades and is considered relatively safe, she said. Patients are followed clinically for changes in their BCCs, and they undergo tumor biopsies before and after the 1-month therapy to measure the treatment's effects on the hedgehog signaling pathway.

Preliminary data are “somewhat promising” in reducing BCC size, Dr. Tang said. The effect has not been as dramatic as with the GDC-0449 study, but neither have the side effects.

'In the patients who have responded, it has changed their lives. We are really excited about it.'

Source DR. TANG

PASADENA, CALIF. — Two drugs — one old, one new — are showing promise in early clinical trials for the treatment of basal cell carcinomas.

If they prove to be useful, clinicians can thank scientists who successfully identified abnormalities in the hedgehog signaling pathway as the mechanism of disease for basal cell carcinoma (BCC), Dr. Jean Tang said at the meeting.

“Every major pharmaceutical company is now interested in the hedgehog pathway, so we may see a lot of treatments in the near future” for BCC and other cancers, said Dr. Tang of Stanford (Calif.) University.

She and her associates are conducting a phase II trial of the experimental Genentech drug GDC-0449 in patients with many BCCs from basal cell nevus syndrome (Gorlin's syndrome), and a separate proof-of-concept study of the antifungal drug itraconazole in patients with small numbers of BCCs who do not have basal cell nevus syndrome.

For GDC-0449, a previous phase I study in 33 patients with locally advanced or metastatic BCC who took the drug for a median of 10 months found that 50%-60% had partial or complete responses and the drug was generally well tolerated (N. Engl. J. Med. 2009;361:1164–72).

Of the 41 patients with basal cell nevus syndrome recruited thus far for the phase II trial — and randomized to 18 months of treatment with GDC-0449 or placebo — 23 patients (with 953 BCC tumors) have more than 1 month of data.

Although the study is still blinded, 15 patients in group A have developed a median of one new BCC during that month, compared with a median of 10 new BCCs in each of the 8 patients in group B, a significant difference that suggests group A may have received the drug and it may be working, Dr. Tang suggested.

In group A, patients started with a median of 252 BCCs and had 127 at the most recent follow-up, a 50% decline. In group B, patients started with 217 BCCs and had 267 at follow-up, a 23% increase in BCCs.

The difference between groups is significant, she said. Existing BCCs in group A also seem to have decreased in size.

“In the patients who have responded, it has changed their lives,” Dr. Tang said. “We are really excited about it.”

Patients in group A, however, were significantly more likely to develop dysgeusia (decreased taste sensation). The condition was seen in 14 of 15 patients, compared with none in group B. Seven patients in group A and none in group B reported some hair loss, though this difference was not statistically significant. Two patients in group A stopped treatment because of dysgeusia and hair loss, compared with none in group B.

These side effects may be acceptable to patients with basal cell nevus syndrome but probably not to patients with only one or two BCCs, Dr. Tang noted.

For the latter group, a proof-of-concept trial has randomized eight patients thus far to 1 month of treatment with 400 mg/day of oral itraconazole, a drug that has been on the market for approximately 2 decades and is considered relatively safe, she said. Patients are followed clinically for changes in their BCCs, and they undergo tumor biopsies before and after the 1-month therapy to measure the treatment's effects on the hedgehog signaling pathway.

Preliminary data are “somewhat promising” in reducing BCC size, Dr. Tang said. The effect has not been as dramatic as with the GDC-0449 study, but neither have the side effects.

'In the patients who have responded, it has changed their lives. We are really excited about it.'

Source DR. TANG

PASADENA, CALIF. — Two drugs — one old, one new — are showing promise in early clinical trials for the treatment of basal cell carcinomas.

If they prove to be useful, clinicians can thank scientists who successfully identified abnormalities in the hedgehog signaling pathway as the mechanism of disease for basal cell carcinoma (BCC), Dr. Jean Tang said at the meeting.

“Every major pharmaceutical company is now interested in the hedgehog pathway, so we may see a lot of treatments in the near future” for BCC and other cancers, said Dr. Tang of Stanford (Calif.) University.

She and her associates are conducting a phase II trial of the experimental Genentech drug GDC-0449 in patients with many BCCs from basal cell nevus syndrome (Gorlin's syndrome), and a separate proof-of-concept study of the antifungal drug itraconazole in patients with small numbers of BCCs who do not have basal cell nevus syndrome.

For GDC-0449, a previous phase I study in 33 patients with locally advanced or metastatic BCC who took the drug for a median of 10 months found that 50%-60% had partial or complete responses and the drug was generally well tolerated (N. Engl. J. Med. 2009;361:1164–72).

Of the 41 patients with basal cell nevus syndrome recruited thus far for the phase II trial — and randomized to 18 months of treatment with GDC-0449 or placebo — 23 patients (with 953 BCC tumors) have more than 1 month of data.

Although the study is still blinded, 15 patients in group A have developed a median of one new BCC during that month, compared with a median of 10 new BCCs in each of the 8 patients in group B, a significant difference that suggests group A may have received the drug and it may be working, Dr. Tang suggested.

In group A, patients started with a median of 252 BCCs and had 127 at the most recent follow-up, a 50% decline. In group B, patients started with 217 BCCs and had 267 at follow-up, a 23% increase in BCCs.

The difference between groups is significant, she said. Existing BCCs in group A also seem to have decreased in size.

“In the patients who have responded, it has changed their lives,” Dr. Tang said. “We are really excited about it.”

Patients in group A, however, were significantly more likely to develop dysgeusia (decreased taste sensation). The condition was seen in 14 of 15 patients, compared with none in group B. Seven patients in group A and none in group B reported some hair loss, though this difference was not statistically significant. Two patients in group A stopped treatment because of dysgeusia and hair loss, compared with none in group B.

These side effects may be acceptable to patients with basal cell nevus syndrome but probably not to patients with only one or two BCCs, Dr. Tang noted.

For the latter group, a proof-of-concept trial has randomized eight patients thus far to 1 month of treatment with 400 mg/day of oral itraconazole, a drug that has been on the market for approximately 2 decades and is considered relatively safe, she said. Patients are followed clinically for changes in their BCCs, and they undergo tumor biopsies before and after the 1-month therapy to measure the treatment's effects on the hedgehog signaling pathway.

Preliminary data are “somewhat promising” in reducing BCC size, Dr. Tang said. The effect has not been as dramatic as with the GDC-0449 study, but neither have the side effects.

'In the patients who have responded, it has changed their lives. We are really excited about it.'

Source DR. TANG

MONTEREY, CALIF. – Have you searched for your name on the Internet? Your patients have.

“Your patients are Googling you,” and some of them probably are rating your performance as a doctor on one of the many physician-rating sites or generic rating sites, Dr. Clifford Warren Lober said.

Here's the problem: The patients most likely to rate you are those who are angry with you, or those who think you walk on water. And it's not just patients who are posting comments about you, but previous patients, ex-employees, former spouses, or anyone else who knows you, said Dr. Lober, a dermatologist and attorney in Kissimmee, Fla.

Online comments might be made anonymously, persist for years on the Internet, be accessed by anyone with a computer, and be replicated on other Web sites beyond the original. If you discover comments about you that you think are harmful to your reputation, your attempts to remedy the situation may backfire and instead “optimize” the content by bringing more attention to the posted statement, amplifying its negativity, he said.

Legal remedies are few and complicated. “There is a morass of legal defenses and privileges that protect the offending person,” Dr. Lober said.

So what is the best way to manage your online reputation? One strategy is to minimize the impact of negative online information through search-engine optimization, he suggested.

In practice, this means blitzing the Web with your own content to crowd out comments by others. “You want to occupy the first three pages of the rating sites” and the search-engine results pages if possible, Dr. Lober said, adding that most people don't look beyond the first three pages of results.

This can be done by establishing multiple Web sites, each with numerous internal page links, external high-traffic links, significant content on each of your home pages, and other features that make these the sites that show up when someone searches your name.

Establishing a deep social network presence helps, too. Create accounts on Facebook, Twitter, LinkedIn, ZoomInfo, Connectbeam, Yahoo Profile, Google Profile, MSN Profile, Wetpaint, Naymz, Jigsaw, Ning, and others, he suggested. Ideally, get on sites that feature RSS (Really Simple Syndication) feeds so that information posted on one site transfers to others.

Other prongs in this strategy include issuing press releases by using Internet publication sites, establishing one or more blogs in your name, and using pay-per-click advertising.

Sound overwhelming? Innovative entrepreneurs thought that it might, so several Internet reputation-management companies have formed to do some of this work for you – for a fee, of course. These include companies such as Reputation Repair & Management, Internet Reputation Management, and ReputationDefender, Dr. Lober said.

If, instead, you want to try to get a specific offensive statement removed from the Web, seek legal counsel to guide you, he advised.

First, the statement must be determined to meet the legal definition of defamation. If it does, the next step is to determine whethr the person who wrote it is covered by any one of several standard legal defenses. If that's not an issue, check the terms and conditions listed by the Internet service provider (ISP) of the site where the comment appeared, to see if the ISP made any promises or assurances about the content on the site. If you contact the ISP, it might take the comment down.

Normally, ISPs are immune from lawsuits over statements made by others on its service; they resemble telephone companies more than newspapers in that respect, he said.

You or your lawyer can request that the courts issue a subpoena to try to compel the person who made the statement (even an anonymous poster) to remedy the situation, but this process is time consuming and expensive, and the person who posted the comment may be difficult to locate, Dr. Lober cautioned.

And if you sue, the defendant may try to frame your action as a SLAPP (strategic litigation against public participation) suit intended to muzzle critics and restrict freedom of speech.

Some states have anti-SLAPP laws that could leave you paying the defendant's attorney fees and costs, and make you vulnerable to a countersuit by the defendant.

Better to try to “manage” your online reputation than to try to legally defend it, he suggested.

Disclosures: Dr. Lober reported having no pertinent conflicts of interest.

MONTEREY, CALIF. – Have you searched for your name on the Internet? Your patients have.

“Your patients are Googling you,” and some of them probably are rating your performance as a doctor on one of the many physician-rating sites or generic rating sites, Dr. Clifford Warren Lober said.

Here's the problem: The patients most likely to rate you are those who are angry with you, or those who think you walk on water. And it's not just patients who are posting comments about you, but previous patients, ex-employees, former spouses, or anyone else who knows you, said Dr. Lober, a dermatologist and attorney in Kissimmee, Fla.

Online comments might be made anonymously, persist for years on the Internet, be accessed by anyone with a computer, and be replicated on other Web sites beyond the original. If you discover comments about you that you think are harmful to your reputation, your attempts to remedy the situation may backfire and instead “optimize” the content by bringing more attention to the posted statement, amplifying its negativity, he said.

Legal remedies are few and complicated. “There is a morass of legal defenses and privileges that protect the offending person,” Dr. Lober said.

So what is the best way to manage your online reputation? One strategy is to minimize the impact of negative online information through search-engine optimization, he suggested.

In practice, this means blitzing the Web with your own content to crowd out comments by others. “You want to occupy the first three pages of the rating sites” and the search-engine results pages if possible, Dr. Lober said, adding that most people don't look beyond the first three pages of results.

This can be done by establishing multiple Web sites, each with numerous internal page links, external high-traffic links, significant content on each of your home pages, and other features that make these the sites that show up when someone searches your name.

Establishing a deep social network presence helps, too. Create accounts on Facebook, Twitter, LinkedIn, ZoomInfo, Connectbeam, Yahoo Profile, Google Profile, MSN Profile, Wetpaint, Naymz, Jigsaw, Ning, and others, he suggested. Ideally, get on sites that feature RSS (Really Simple Syndication) feeds so that information posted on one site transfers to others.

Other prongs in this strategy include issuing press releases by using Internet publication sites, establishing one or more blogs in your name, and using pay-per-click advertising.

Sound overwhelming? Innovative entrepreneurs thought that it might, so several Internet reputation-management companies have formed to do some of this work for you – for a fee, of course. These include companies such as Reputation Repair & Management, Internet Reputation Management, and ReputationDefender, Dr. Lober said.

If, instead, you want to try to get a specific offensive statement removed from the Web, seek legal counsel to guide you, he advised.

First, the statement must be determined to meet the legal definition of defamation. If it does, the next step is to determine whethr the person who wrote it is covered by any one of several standard legal defenses. If that's not an issue, check the terms and conditions listed by the Internet service provider (ISP) of the site where the comment appeared, to see if the ISP made any promises or assurances about the content on the site. If you contact the ISP, it might take the comment down.

Normally, ISPs are immune from lawsuits over statements made by others on its service; they resemble telephone companies more than newspapers in that respect, he said.

You or your lawyer can request that the courts issue a subpoena to try to compel the person who made the statement (even an anonymous poster) to remedy the situation, but this process is time consuming and expensive, and the person who posted the comment may be difficult to locate, Dr. Lober cautioned.

And if you sue, the defendant may try to frame your action as a SLAPP (strategic litigation against public participation) suit intended to muzzle critics and restrict freedom of speech.

Some states have anti-SLAPP laws that could leave you paying the defendant's attorney fees and costs, and make you vulnerable to a countersuit by the defendant.

Better to try to “manage” your online reputation than to try to legally defend it, he suggested.

Disclosures: Dr. Lober reported having no pertinent conflicts of interest.

MONTEREY, CALIF. – Have you searched for your name on the Internet? Your patients have.

“Your patients are Googling you,” and some of them probably are rating your performance as a doctor on one of the many physician-rating sites or generic rating sites, Dr. Clifford Warren Lober said.

Here's the problem: The patients most likely to rate you are those who are angry with you, or those who think you walk on water. And it's not just patients who are posting comments about you, but previous patients, ex-employees, former spouses, or anyone else who knows you, said Dr. Lober, a dermatologist and attorney in Kissimmee, Fla.

Online comments might be made anonymously, persist for years on the Internet, be accessed by anyone with a computer, and be replicated on other Web sites beyond the original. If you discover comments about you that you think are harmful to your reputation, your attempts to remedy the situation may backfire and instead “optimize” the content by bringing more attention to the posted statement, amplifying its negativity, he said.

Legal remedies are few and complicated. “There is a morass of legal defenses and privileges that protect the offending person,” Dr. Lober said.

So what is the best way to manage your online reputation? One strategy is to minimize the impact of negative online information through search-engine optimization, he suggested.

In practice, this means blitzing the Web with your own content to crowd out comments by others. “You want to occupy the first three pages of the rating sites” and the search-engine results pages if possible, Dr. Lober said, adding that most people don't look beyond the first three pages of results.

This can be done by establishing multiple Web sites, each with numerous internal page links, external high-traffic links, significant content on each of your home pages, and other features that make these the sites that show up when someone searches your name.

Establishing a deep social network presence helps, too. Create accounts on Facebook, Twitter, LinkedIn, ZoomInfo, Connectbeam, Yahoo Profile, Google Profile, MSN Profile, Wetpaint, Naymz, Jigsaw, Ning, and others, he suggested. Ideally, get on sites that feature RSS (Really Simple Syndication) feeds so that information posted on one site transfers to others.

Other prongs in this strategy include issuing press releases by using Internet publication sites, establishing one or more blogs in your name, and using pay-per-click advertising.

Sound overwhelming? Innovative entrepreneurs thought that it might, so several Internet reputation-management companies have formed to do some of this work for you – for a fee, of course. These include companies such as Reputation Repair & Management, Internet Reputation Management, and ReputationDefender, Dr. Lober said.

If, instead, you want to try to get a specific offensive statement removed from the Web, seek legal counsel to guide you, he advised.

First, the statement must be determined to meet the legal definition of defamation. If it does, the next step is to determine whethr the person who wrote it is covered by any one of several standard legal defenses. If that's not an issue, check the terms and conditions listed by the Internet service provider (ISP) of the site where the comment appeared, to see if the ISP made any promises or assurances about the content on the site. If you contact the ISP, it might take the comment down.

Normally, ISPs are immune from lawsuits over statements made by others on its service; they resemble telephone companies more than newspapers in that respect, he said.

You or your lawyer can request that the courts issue a subpoena to try to compel the person who made the statement (even an anonymous poster) to remedy the situation, but this process is time consuming and expensive, and the person who posted the comment may be difficult to locate, Dr. Lober cautioned.

And if you sue, the defendant may try to frame your action as a SLAPP (strategic litigation against public participation) suit intended to muzzle critics and restrict freedom of speech.

Some states have anti-SLAPP laws that could leave you paying the defendant's attorney fees and costs, and make you vulnerable to a countersuit by the defendant.

Better to try to “manage” your online reputation than to try to legally defend it, he suggested.

Disclosures: Dr. Lober reported having no pertinent conflicts of interest.

Major Finding: Adults with migraines and a history of head or neck injury had more frequent headaches than did migraineurs without injuries (16 vs. 13 days/month, respectively) as well as disabling headaches (mean score on the Headache Impact Test-6, 60 vs. 54, respectively) and higher rates of various comorbidities.

Data Source: Self-administered electronic questionnaires completed by 1,348 clinic patients.

Disclosures: Dr. Tietjen has received research grants from GlaxoSmithKline and consulting fees and honoraria from MAP Pharmaceuticals. A grant from the American Headache Society's Women's Issues Section funded the study.

LOS ANGELES – Migraine patients with a history of head or neck injury reported more frequent and disabling headaches and higher rates of a variety of comorbidities than did migraineurs without head or neck injuries in a survey of 1,348 adult patients.

Some migraine features differed significantly between patients with or without a history of head or neck injury, according to responses to electronic questionnaires that were completed by patients seen in clinics for their migraine headaches, Dr. Gretchen E. Tietjen reported.

In the survey, Dr. Tietjen and her associates gathered information from 373 patients with a history of head or neck injury. The patients with head or neck injury averaged 16 days with headaches per month, compared with 13 days per month in 975 noninjured patients.

Chronic headaches (defined as headaches on more than 15 days/month) were a problem for 42% of patients with a history of injury and 31% of those who had not been injured.

Scores on the Headache Impact Test–6 averaged 60 in the injured group and 54 in the noninjured group. This difference suggested a greater impact of headaches on daily life in the injured group.

“One thing I wasn't expecting” was a consistent difference between groups in prevalence rates of comorbidities, said Dr. Tietjen, who serves as professor and chair of the neurology department at the University of Toledo (Ohio).

Comparing the injured group with the noninjured group, prevalence rates were 52% vs. 35% for depression, 40% vs. 27% for anxiety, 37% vs. 21% for arthritis, and 30% vs. 21% for irritable bowel syndrome.

Other differences in prevalence rates were 16% vs. 7% for fibromyalgia, 11% vs. 6% for sleep apnea, 9% vs. 5% for interstitial cystitis, and 17% vs. 10% for uterine fibroids, respectively.

Each of these differences between groups was statistically significant.

Patients developed symptoms of these comorbidities and were diagnosed at an earlier age if they had a history of injury than if they had not been injured. The onset of depression, anxiety, sleep apnea, and fibromyalgia occurred at a significantly earlier age in those who had been injured than in those who had not, she said.

Patients who had a history of injury were significantly more likely to have a history of substance abuse (24%), compared with noninjured patients (16%), and to have an education level no higher than high school (32% vs. 25%, respectively).

Among patients with a history of head or neck injury in whom the timing of the injury was known, the 45 patients whose migraines started concurrently with the injury were less likely to have migraine with aura, compared with the 170 patients whose migraines started prior to the injury or the 109 patients whose migraines began after the injury.

The migraines came with aura in 22% of the subgroup with concurrent-onset migraine, 45% of the subgroup with migraine before their injury, and 47% of those with migraine after their injury.

Patients in the concurrent-onset group also were statistically significantly younger (average age, 40 years), compared with the patients whose migraines started before the injury (42 years) or patients whose migraines started after injury (44 years).

The questionnaire did not ask about the nature or causes of the head and neck injuries.

Patients were asked about the number of head and neck injuries, their age at the first one, their age at the worst injury, whether or not there was a loss of consciousness associated with the injury, and when they were diagnosed with migraine headache.

A physician in the audience asked Dr. Tietjen whether the head injuries might have contributed to the development of psychosomatic syndromes that increased the prevalence of comorbidities.

Dr. Tietjen doubted that this was the case, given the wide nature of the comorbidities that included conditions such as uterine fibroids.

“I think it might be more mental/physiologic than just psychological,” she said.

Major Finding: Adults with migraines and a history of head or neck injury had more frequent headaches than did migraineurs without injuries (16 vs. 13 days/month, respectively) as well as disabling headaches (mean score on the Headache Impact Test-6, 60 vs. 54, respectively) and higher rates of various comorbidities.

Data Source: Self-administered electronic questionnaires completed by 1,348 clinic patients.

Disclosures: Dr. Tietjen has received research grants from GlaxoSmithKline and consulting fees and honoraria from MAP Pharmaceuticals. A grant from the American Headache Society's Women's Issues Section funded the study.

LOS ANGELES – Migraine patients with a history of head or neck injury reported more frequent and disabling headaches and higher rates of a variety of comorbidities than did migraineurs without head or neck injuries in a survey of 1,348 adult patients.

Some migraine features differed significantly between patients with or without a history of head or neck injury, according to responses to electronic questionnaires that were completed by patients seen in clinics for their migraine headaches, Dr. Gretchen E. Tietjen reported.

In the survey, Dr. Tietjen and her associates gathered information from 373 patients with a history of head or neck injury. The patients with head or neck injury averaged 16 days with headaches per month, compared with 13 days per month in 975 noninjured patients.

Chronic headaches (defined as headaches on more than 15 days/month) were a problem for 42% of patients with a history of injury and 31% of those who had not been injured.

Scores on the Headache Impact Test–6 averaged 60 in the injured group and 54 in the noninjured group. This difference suggested a greater impact of headaches on daily life in the injured group.

“One thing I wasn't expecting” was a consistent difference between groups in prevalence rates of comorbidities, said Dr. Tietjen, who serves as professor and chair of the neurology department at the University of Toledo (Ohio).

Comparing the injured group with the noninjured group, prevalence rates were 52% vs. 35% for depression, 40% vs. 27% for anxiety, 37% vs. 21% for arthritis, and 30% vs. 21% for irritable bowel syndrome.

Other differences in prevalence rates were 16% vs. 7% for fibromyalgia, 11% vs. 6% for sleep apnea, 9% vs. 5% for interstitial cystitis, and 17% vs. 10% for uterine fibroids, respectively.

Each of these differences between groups was statistically significant.

Patients developed symptoms of these comorbidities and were diagnosed at an earlier age if they had a history of injury than if they had not been injured. The onset of depression, anxiety, sleep apnea, and fibromyalgia occurred at a significantly earlier age in those who had been injured than in those who had not, she said.

Patients who had a history of injury were significantly more likely to have a history of substance abuse (24%), compared with noninjured patients (16%), and to have an education level no higher than high school (32% vs. 25%, respectively).

Among patients with a history of head or neck injury in whom the timing of the injury was known, the 45 patients whose migraines started concurrently with the injury were less likely to have migraine with aura, compared with the 170 patients whose migraines started prior to the injury or the 109 patients whose migraines began after the injury.

The migraines came with aura in 22% of the subgroup with concurrent-onset migraine, 45% of the subgroup with migraine before their injury, and 47% of those with migraine after their injury.

Patients in the concurrent-onset group also were statistically significantly younger (average age, 40 years), compared with the patients whose migraines started before the injury (42 years) or patients whose migraines started after injury (44 years).

The questionnaire did not ask about the nature or causes of the head and neck injuries.

Patients were asked about the number of head and neck injuries, their age at the first one, their age at the worst injury, whether or not there was a loss of consciousness associated with the injury, and when they were diagnosed with migraine headache.

A physician in the audience asked Dr. Tietjen whether the head injuries might have contributed to the development of psychosomatic syndromes that increased the prevalence of comorbidities.

Dr. Tietjen doubted that this was the case, given the wide nature of the comorbidities that included conditions such as uterine fibroids.

“I think it might be more mental/physiologic than just psychological,” she said.

Major Finding: Adults with migraines and a history of head or neck injury had more frequent headaches than did migraineurs without injuries (16 vs. 13 days/month, respectively) as well as disabling headaches (mean score on the Headache Impact Test-6, 60 vs. 54, respectively) and higher rates of various comorbidities.

Data Source: Self-administered electronic questionnaires completed by 1,348 clinic patients.

Disclosures: Dr. Tietjen has received research grants from GlaxoSmithKline and consulting fees and honoraria from MAP Pharmaceuticals. A grant from the American Headache Society's Women's Issues Section funded the study.

LOS ANGELES – Migraine patients with a history of head or neck injury reported more frequent and disabling headaches and higher rates of a variety of comorbidities than did migraineurs without head or neck injuries in a survey of 1,348 adult patients.

Some migraine features differed significantly between patients with or without a history of head or neck injury, according to responses to electronic questionnaires that were completed by patients seen in clinics for their migraine headaches, Dr. Gretchen E. Tietjen reported.

In the survey, Dr. Tietjen and her associates gathered information from 373 patients with a history of head or neck injury. The patients with head or neck injury averaged 16 days with headaches per month, compared with 13 days per month in 975 noninjured patients.

Chronic headaches (defined as headaches on more than 15 days/month) were a problem for 42% of patients with a history of injury and 31% of those who had not been injured.

Scores on the Headache Impact Test–6 averaged 60 in the injured group and 54 in the noninjured group. This difference suggested a greater impact of headaches on daily life in the injured group.

“One thing I wasn't expecting” was a consistent difference between groups in prevalence rates of comorbidities, said Dr. Tietjen, who serves as professor and chair of the neurology department at the University of Toledo (Ohio).

Comparing the injured group with the noninjured group, prevalence rates were 52% vs. 35% for depression, 40% vs. 27% for anxiety, 37% vs. 21% for arthritis, and 30% vs. 21% for irritable bowel syndrome.

Other differences in prevalence rates were 16% vs. 7% for fibromyalgia, 11% vs. 6% for sleep apnea, 9% vs. 5% for interstitial cystitis, and 17% vs. 10% for uterine fibroids, respectively.

Each of these differences between groups was statistically significant.

Patients developed symptoms of these comorbidities and were diagnosed at an earlier age if they had a history of injury than if they had not been injured. The onset of depression, anxiety, sleep apnea, and fibromyalgia occurred at a significantly earlier age in those who had been injured than in those who had not, she said.

Patients who had a history of injury were significantly more likely to have a history of substance abuse (24%), compared with noninjured patients (16%), and to have an education level no higher than high school (32% vs. 25%, respectively).

Among patients with a history of head or neck injury in whom the timing of the injury was known, the 45 patients whose migraines started concurrently with the injury were less likely to have migraine with aura, compared with the 170 patients whose migraines started prior to the injury or the 109 patients whose migraines began after the injury.

The migraines came with aura in 22% of the subgroup with concurrent-onset migraine, 45% of the subgroup with migraine before their injury, and 47% of those with migraine after their injury.

Patients in the concurrent-onset group also were statistically significantly younger (average age, 40 years), compared with the patients whose migraines started before the injury (42 years) or patients whose migraines started after injury (44 years).

The questionnaire did not ask about the nature or causes of the head and neck injuries.

Patients were asked about the number of head and neck injuries, their age at the first one, their age at the worst injury, whether or not there was a loss of consciousness associated with the injury, and when they were diagnosed with migraine headache.

A physician in the audience asked Dr. Tietjen whether the head injuries might have contributed to the development of psychosomatic syndromes that increased the prevalence of comorbidities.

Dr. Tietjen doubted that this was the case, given the wide nature of the comorbidities that included conditions such as uterine fibroids.

“I think it might be more mental/physiologic than just psychological,” she said.

Major Finding: Headaches, initially reported by 46% of patients soon after injury, still occurred in 48% at 3 months, 44% at 6 months, and 46% at 12 months.

Data Source: Prospective study of 377 consecutive admissions to acute rehabilitation facilities for traumatic brain injury.

Disclosures: Dr. Lucas said she has no relevant conflicts of interest. The National Institute on Disability and Rehabilitation Research funded the study.

LOS ANGELES – Nearly half of 377 patients with traumatic brain injury reported postinjury headaches that persisted during a year of follow-up in a prospective study.

The prevalence of headaches in the cohort increased from 18% before the injury to 46% soon after injury, according to patient reports during rehabilitation hospitalization for TBI. In phone interviews after discharge at 3, 6, and 12 months post injury, headaches were reported by 48%, 44%, and 46%, respectively.

The persistence of the headaches took senior investigator Dr. Sylvia Lucas and her colleagues by surprise, because previous data have suggested that 18%-22% of posttraumatic headaches are chronic problems.

Dr. Lucas said that she and her associates also were surprised that most of the headaches in the current study were classified as migraine or tension-type headache, that the presence of preinjury headache seemed to be a risk factor for postinjury headache, and that women were at higher risk for postinjury headache. The findings on types of headache and their persistence could have “important implications for treatment” of posttraumatic headache, said Dr. Lucas, founder and director of the headache center at the University of Washington, Seattle.

Posttraumatic headache is one of the most common persisting symptoms after TBI, occurring in 30%-90% of patients, previous studies suggest. Although most familiar as a salient symptom in soldiers who were exposed to explosive blasts, “it's becoming of great interest in adolescent children who've been in sports concussion injuries,” she said.

The study included consecutive admissions of patients older than 16 years at seven acute rehabilitation facilities for TBI, excluding 79 patients who could not provide consent or answer questions themselves without their families' acting as proxy.

The cause of injury was vehicular trauma in approximately 56%, falls or impacts with flying objects in 28%, violence in 9%, and sports or pedestrian accidents in 4% each. (Percentages were rounded.)

Based on descriptions of symptoms by patients who reported headache, 60% of preinjury headaches were classified as migraine or probable migraine, compared with 48% soon after injury and 54% a year later. Although 25% of preinjury headaches and 37% of headaches soon after injury were deemed “unclassifiable” by investigators using patients' descriptions, over time they gained features that allowed them to be classified in one of the primary headache classifications so that the proportion of “unclassified” headache fell to 19% by 12 months post injury.

“Mostly, patients were classified as migraine with or without aura, or tension-type headache, which is also surprising given the fact that most of these were vehicular injuries,” Dr. Lucas said. Headaches were classified as tension type in 12% before injury, in 7% soon after injury, and in 19% at 12 months. Headaches were classified as cervicogenic in 4% before injury, in 8% soon after injury, and in 5% at 12 months.

Among patients who said had headaches before the injury, 48% reported postinjury headache, compared with 23% of patients who said they did not have headaches before the injury. “Preinjury headache may be a risk factor for posttraumatic headache. This may argue for a common underlying mechanism,” Dr. Lucas said.

The cohort was 71% male and 75% white. Patients had an average age of 43 years, and 84% were able to be discharged to home.

The injury caused posttraumatic amnesia for less than a day in 7% (indicative of a milder head injury), for 1-7 days in 21%, for 8-28 days in 42%, and for 29 or more days in 30%.

“This was primarily a male group; however, all the way along – at baseline, 3 months, 6 months, and 12 months – there was a statistically significant difference in women having more posttraumatic headache than men,” as well as a higher incidence of preinjury headache, Dr. Lucas said. About 40% of men reported headache at all follow-up time points after injury, vs. about 60% of women.

More attention is being directed to adolescent children who've had sports concussion injuries.

Source DR. LUCAS

Major Finding: Headaches, initially reported by 46% of patients soon after injury, still occurred in 48% at 3 months, 44% at 6 months, and 46% at 12 months.

Data Source: Prospective study of 377 consecutive admissions to acute rehabilitation facilities for traumatic brain injury.

Disclosures: Dr. Lucas said she has no relevant conflicts of interest. The National Institute on Disability and Rehabilitation Research funded the study.

LOS ANGELES – Nearly half of 377 patients with traumatic brain injury reported postinjury headaches that persisted during a year of follow-up in a prospective study.

The prevalence of headaches in the cohort increased from 18% before the injury to 46% soon after injury, according to patient reports during rehabilitation hospitalization for TBI. In phone interviews after discharge at 3, 6, and 12 months post injury, headaches were reported by 48%, 44%, and 46%, respectively.

The persistence of the headaches took senior investigator Dr. Sylvia Lucas and her colleagues by surprise, because previous data have suggested that 18%-22% of posttraumatic headaches are chronic problems.

Dr. Lucas said that she and her associates also were surprised that most of the headaches in the current study were classified as migraine or tension-type headache, that the presence of preinjury headache seemed to be a risk factor for postinjury headache, and that women were at higher risk for postinjury headache. The findings on types of headache and their persistence could have “important implications for treatment” of posttraumatic headache, said Dr. Lucas, founder and director of the headache center at the University of Washington, Seattle.

Posttraumatic headache is one of the most common persisting symptoms after TBI, occurring in 30%-90% of patients, previous studies suggest. Although most familiar as a salient symptom in soldiers who were exposed to explosive blasts, “it's becoming of great interest in adolescent children who've been in sports concussion injuries,” she said.

The study included consecutive admissions of patients older than 16 years at seven acute rehabilitation facilities for TBI, excluding 79 patients who could not provide consent or answer questions themselves without their families' acting as proxy.

The cause of injury was vehicular trauma in approximately 56%, falls or impacts with flying objects in 28%, violence in 9%, and sports or pedestrian accidents in 4% each. (Percentages were rounded.)

Based on descriptions of symptoms by patients who reported headache, 60% of preinjury headaches were classified as migraine or probable migraine, compared with 48% soon after injury and 54% a year later. Although 25% of preinjury headaches and 37% of headaches soon after injury were deemed “unclassifiable” by investigators using patients' descriptions, over time they gained features that allowed them to be classified in one of the primary headache classifications so that the proportion of “unclassified” headache fell to 19% by 12 months post injury.

“Mostly, patients were classified as migraine with or without aura, or tension-type headache, which is also surprising given the fact that most of these were vehicular injuries,” Dr. Lucas said. Headaches were classified as tension type in 12% before injury, in 7% soon after injury, and in 19% at 12 months. Headaches were classified as cervicogenic in 4% before injury, in 8% soon after injury, and in 5% at 12 months.

Among patients who said had headaches before the injury, 48% reported postinjury headache, compared with 23% of patients who said they did not have headaches before the injury. “Preinjury headache may be a risk factor for posttraumatic headache. This may argue for a common underlying mechanism,” Dr. Lucas said.

The cohort was 71% male and 75% white. Patients had an average age of 43 years, and 84% were able to be discharged to home.

The injury caused posttraumatic amnesia for less than a day in 7% (indicative of a milder head injury), for 1-7 days in 21%, for 8-28 days in 42%, and for 29 or more days in 30%.

“This was primarily a male group; however, all the way along – at baseline, 3 months, 6 months, and 12 months – there was a statistically significant difference in women having more posttraumatic headache than men,” as well as a higher incidence of preinjury headache, Dr. Lucas said. About 40% of men reported headache at all follow-up time points after injury, vs. about 60% of women.

More attention is being directed to adolescent children who've had sports concussion injuries.

Source DR. LUCAS

Major Finding: Headaches, initially reported by 46% of patients soon after injury, still occurred in 48% at 3 months, 44% at 6 months, and 46% at 12 months.

Data Source: Prospective study of 377 consecutive admissions to acute rehabilitation facilities for traumatic brain injury.

Disclosures: Dr. Lucas said she has no relevant conflicts of interest. The National Institute on Disability and Rehabilitation Research funded the study.

LOS ANGELES – Nearly half of 377 patients with traumatic brain injury reported postinjury headaches that persisted during a year of follow-up in a prospective study.

The prevalence of headaches in the cohort increased from 18% before the injury to 46% soon after injury, according to patient reports during rehabilitation hospitalization for TBI. In phone interviews after discharge at 3, 6, and 12 months post injury, headaches were reported by 48%, 44%, and 46%, respectively.

The persistence of the headaches took senior investigator Dr. Sylvia Lucas and her colleagues by surprise, because previous data have suggested that 18%-22% of posttraumatic headaches are chronic problems.

Dr. Lucas said that she and her associates also were surprised that most of the headaches in the current study were classified as migraine or tension-type headache, that the presence of preinjury headache seemed to be a risk factor for postinjury headache, and that women were at higher risk for postinjury headache. The findings on types of headache and their persistence could have “important implications for treatment” of posttraumatic headache, said Dr. Lucas, founder and director of the headache center at the University of Washington, Seattle.

Posttraumatic headache is one of the most common persisting symptoms after TBI, occurring in 30%-90% of patients, previous studies suggest. Although most familiar as a salient symptom in soldiers who were exposed to explosive blasts, “it's becoming of great interest in adolescent children who've been in sports concussion injuries,” she said.

The study included consecutive admissions of patients older than 16 years at seven acute rehabilitation facilities for TBI, excluding 79 patients who could not provide consent or answer questions themselves without their families' acting as proxy.

The cause of injury was vehicular trauma in approximately 56%, falls or impacts with flying objects in 28%, violence in 9%, and sports or pedestrian accidents in 4% each. (Percentages were rounded.)

Based on descriptions of symptoms by patients who reported headache, 60% of preinjury headaches were classified as migraine or probable migraine, compared with 48% soon after injury and 54% a year later. Although 25% of preinjury headaches and 37% of headaches soon after injury were deemed “unclassifiable” by investigators using patients' descriptions, over time they gained features that allowed them to be classified in one of the primary headache classifications so that the proportion of “unclassified” headache fell to 19% by 12 months post injury.

“Mostly, patients were classified as migraine with or without aura, or tension-type headache, which is also surprising given the fact that most of these were vehicular injuries,” Dr. Lucas said. Headaches were classified as tension type in 12% before injury, in 7% soon after injury, and in 19% at 12 months. Headaches were classified as cervicogenic in 4% before injury, in 8% soon after injury, and in 5% at 12 months.

Among patients who said had headaches before the injury, 48% reported postinjury headache, compared with 23% of patients who said they did not have headaches before the injury. “Preinjury headache may be a risk factor for posttraumatic headache. This may argue for a common underlying mechanism,” Dr. Lucas said.

The cohort was 71% male and 75% white. Patients had an average age of 43 years, and 84% were able to be discharged to home.

The injury caused posttraumatic amnesia for less than a day in 7% (indicative of a milder head injury), for 1-7 days in 21%, for 8-28 days in 42%, and for 29 or more days in 30%.

“This was primarily a male group; however, all the way along – at baseline, 3 months, 6 months, and 12 months – there was a statistically significant difference in women having more posttraumatic headache than men,” as well as a higher incidence of preinjury headache, Dr. Lucas said. About 40% of men reported headache at all follow-up time points after injury, vs. about 60% of women.

More attention is being directed to adolescent children who've had sports concussion injuries.

Source DR. LUCAS

SAN FRANCISCO – An intensive smoking-cessation program helped 33% of 202 patients in drug treatment quit smoking, an intent-to-treat analysis found.

A high proportion of patients in treatment for substance use also smoke cigarettes and have a hard time quitting, with previous studies suggesting quit rates of 5%-12%, Dr. Milan Khara said at the meeting.

The study enrolled 252 patients who were in drug treatment programs in 8 weeks of group therapy for smoking cessation plus free pharmacotherapy for smoking cessation during the group therapy and for up to an additional 18 weeks, for a total program length of 26 weeks, said Dr. Khara of the University of British Columbia, Vancouver.

The overall quit-smoking rate of 33% in the intent-to-treat analysis was exceeded by a quit rate of 43% among 152 patients who completed the program.

Among these completers, the quit rate was 51% in those who attended the 8 weeks of smoking-cessation group therapy and participated in after-care, compared with 18% of completers who only attended the 8 weeks of group therapy. About 80% of people in drug treatment programs smoke tobacco. “Within addiction services, we've largely had a blind spot about tobacco,” Dr. Khara said. “We often believe that these patients don't want to quit smoking,” but other studies have shown that 44%-80% of patients in drug treatment expressed interest in quitting.

Disclosures: Dr. Khara has received funding from or been a consultant for Pfizer and Johnson & Johnson, which make smoking-cessation medications. Johnson & Johnson and divisions of the Canadian government funded provision of medications in the study.

SAN FRANCISCO – An intensive smoking-cessation program helped 33% of 202 patients in drug treatment quit smoking, an intent-to-treat analysis found.

A high proportion of patients in treatment for substance use also smoke cigarettes and have a hard time quitting, with previous studies suggesting quit rates of 5%-12%, Dr. Milan Khara said at the meeting.

The study enrolled 252 patients who were in drug treatment programs in 8 weeks of group therapy for smoking cessation plus free pharmacotherapy for smoking cessation during the group therapy and for up to an additional 18 weeks, for a total program length of 26 weeks, said Dr. Khara of the University of British Columbia, Vancouver.

The overall quit-smoking rate of 33% in the intent-to-treat analysis was exceeded by a quit rate of 43% among 152 patients who completed the program.

Among these completers, the quit rate was 51% in those who attended the 8 weeks of smoking-cessation group therapy and participated in after-care, compared with 18% of completers who only attended the 8 weeks of group therapy. About 80% of people in drug treatment programs smoke tobacco. “Within addiction services, we've largely had a blind spot about tobacco,” Dr. Khara said. “We often believe that these patients don't want to quit smoking,” but other studies have shown that 44%-80% of patients in drug treatment expressed interest in quitting.

Disclosures: Dr. Khara has received funding from or been a consultant for Pfizer and Johnson & Johnson, which make smoking-cessation medications. Johnson & Johnson and divisions of the Canadian government funded provision of medications in the study.

SAN FRANCISCO – An intensive smoking-cessation program helped 33% of 202 patients in drug treatment quit smoking, an intent-to-treat analysis found.

A high proportion of patients in treatment for substance use also smoke cigarettes and have a hard time quitting, with previous studies suggesting quit rates of 5%-12%, Dr. Milan Khara said at the meeting.

The study enrolled 252 patients who were in drug treatment programs in 8 weeks of group therapy for smoking cessation plus free pharmacotherapy for smoking cessation during the group therapy and for up to an additional 18 weeks, for a total program length of 26 weeks, said Dr. Khara of the University of British Columbia, Vancouver.

The overall quit-smoking rate of 33% in the intent-to-treat analysis was exceeded by a quit rate of 43% among 152 patients who completed the program.

Among these completers, the quit rate was 51% in those who attended the 8 weeks of smoking-cessation group therapy and participated in after-care, compared with 18% of completers who only attended the 8 weeks of group therapy. About 80% of people in drug treatment programs smoke tobacco. “Within addiction services, we've largely had a blind spot about tobacco,” Dr. Khara said. “We often believe that these patients don't want to quit smoking,” but other studies have shown that 44%-80% of patients in drug treatment expressed interest in quitting.

Disclosures: Dr. Khara has received funding from or been a consultant for Pfizer and Johnson & Johnson, which make smoking-cessation medications. Johnson & Johnson and divisions of the Canadian government funded provision of medications in the study.

PASADENA, CALIF. - Recent enthusiasm for treating hemangiomas with propranolol has been tempered by reports of life-threatening events in three infants.

"We're wrestling with the propranolol issue in our practice now. There has to be a significant amount of counseling" of patients and their families while clinicians figure out the safest protocols for propranolol use, Dr. Lawrence F. Eichenfield said at the meeting.

The propranolol-for-hemangiomas story started several years ago when French physicians prescribed high-dose prednisolone for severe hemangiomas in four infants, noticed they were developing high blood pressure secondary to the corticosteroid, and put them on a beta-blocker for the high blood pressure. After a few days of beta-blocker therapy, the hemangiomas started disappearing at a much faster rate than they had on the corticosteroid alone.

The physicians then went directly to propranolol therapy for severe hemangiomas in seven more infants, bypassing the corticosteroid. On a dose of 2-3 mg/kg per day, "they saw a similar incredible response to their hemangiomas," with softening and change in color from red to purple noted in all infants at 24 hours, Dr. Eichenfield said (N. Engl. J. Med. 2008;358:2649-51).

The French series expanded to 32 children with severe hemangiomas at a mean age of 4 months, and therapeutic effects were seen in all cases, with a mean treatment duration of 6 months (Pediatrics 2009;124:e423-31).

Photo courtesy Dr. Katherine B. Puttgen

"Now, there are at least 50 articles in the literature in the past 9 months about propranolol, as it expands from the pediatric dermatology hands to others around the world," said Dr. Eichenfield, director of pediatric and adolescent dermatology at Rady Children's Hospital, San Diego. "It’s an incredible drug, but not without its issues."

The most alarming issues appear to be idiosyncratic events with hypotension, hypoglycemia, hypothermia, bradycardia, or asthma exacerbation. Three children developed life-threatening reactions (Arch. Dermatol. 2010;146:775-8).

The first case was an 11-month-old with a periocular hemangioma who titrated up on propranolol dosing for 2 weeks and had been on a stable dose of propranolol for 3 weeks. The infant was a little fussy one night, got a propranolol dose the next morning, and 2 hours later was pale, cold, clammy, and unresponsive. After resuscitation at a hospital, the child was reported to be doing well.

Photo courtesy Dr. Katherine B. Puttgen

The second case was an 18-month-old with a hemangioma on the nasal tip who had been on a very low dose of propranolol (1.25 mg/kg) for months. Because of a slight respiratory infection, the propranolol was withheld and restarted at a 6 p.m. dosing when the child got better. Thirteen hours later the child was found cold, clammy, and unresponsive. He had a 10-minute seizure and a second seizure on the way to the hospital, where he was found to have a serum glucose of 24 mg/dL. He responded to resuscitation.

In the third case, another child with a nasal tip hemangioma had been on 2 mg/kg per day of propranolol for 8.5 months. Two and a half hours after a breakfast dose, the child was found limp, pale, and tachypneic, and was taken to a hospital, where respiratory syncytial virus infection was diagnosed.

It's not clear what precipitated these crises, Dr. Eichenfield said. And not much is known about how best to use the drug for hemangiomas or how it works for this indication. Even in children whose hemangiomas do not respond to corticosteroids, propranolol often can produce "an incredible clinical response," he said. "You really get them down to essentially nothing very early on. We're quite pleased with those results."

Propranolol has a long history of use in children with heart disease, but not for hemangiomas.

Some physicians admit children who are initiating propranolol for hemangioma treatment, others treat on an outpatient basis. At Dr. Eichenfield's institution, they admit children who are starting the drug in the first 3 months of life, but treat others as outpatients.

The conventional dose is 2-3 mg/kg per day, but it's unclear if there's a dose response, and if patients may do better on 3 mg/kg per day than on the lower dose. Probably half of physicians prescribe a t.i.d. dosage, and others use b.i.d., he said.

It's unclear how long treatment is needed, but "there’s no question that we can get a rebound with propranolol" if the drug is stopped, he said.

Physicians who treat hemangiomas with propranolol should have a clear protocol, Dr. Eichenfield advised. "We'll share our written protocol" with physicians who request it, he said. Dermatologists should collaborate with a pediatrician and possibly a cardiologist on these cases, he added. Written materials for the patients' families and pediatricians can be helpful.

An international, multicenter collaborative study of propranolol for hemangiomas is underway.

Topical beta-blockers also have been considered for hemangiomas. Preliminary data suggest they may produce a response in superficial, flat lesions. But topical beta-blockers also can have systemic side effects. Will they benefit infants with hemangiomas and be safe? "I don’t know. It's a good idea. We’ll see," he said.

Disclosures: Dr. Eichenfield said he has no pertinent conflicts of interest. A member of his division at the university is the primary investigator in a study of propranolol for hemangiomas.

PASADENA, CALIF. - Recent enthusiasm for treating hemangiomas with propranolol has been tempered by reports of life-threatening events in three infants.

"We're wrestling with the propranolol issue in our practice now. There has to be a significant amount of counseling" of patients and their families while clinicians figure out the safest protocols for propranolol use, Dr. Lawrence F. Eichenfield said at the meeting.

The propranolol-for-hemangiomas story started several years ago when French physicians prescribed high-dose prednisolone for severe hemangiomas in four infants, noticed they were developing high blood pressure secondary to the corticosteroid, and put them on a beta-blocker for the high blood pressure. After a few days of beta-blocker therapy, the hemangiomas started disappearing at a much faster rate than they had on the corticosteroid alone.

The physicians then went directly to propranolol therapy for severe hemangiomas in seven more infants, bypassing the corticosteroid. On a dose of 2-3 mg/kg per day, "they saw a similar incredible response to their hemangiomas," with softening and change in color from red to purple noted in all infants at 24 hours, Dr. Eichenfield said (N. Engl. J. Med. 2008;358:2649-51).

The French series expanded to 32 children with severe hemangiomas at a mean age of 4 months, and therapeutic effects were seen in all cases, with a mean treatment duration of 6 months (Pediatrics 2009;124:e423-31).

Photo courtesy Dr. Katherine B. Puttgen

"Now, there are at least 50 articles in the literature in the past 9 months about propranolol, as it expands from the pediatric dermatology hands to others around the world," said Dr. Eichenfield, director of pediatric and adolescent dermatology at Rady Children's Hospital, San Diego. "It’s an incredible drug, but not without its issues."

The most alarming issues appear to be idiosyncratic events with hypotension, hypoglycemia, hypothermia, bradycardia, or asthma exacerbation. Three children developed life-threatening reactions (Arch. Dermatol. 2010;146:775-8).

The first case was an 11-month-old with a periocular hemangioma who titrated up on propranolol dosing for 2 weeks and had been on a stable dose of propranolol for 3 weeks. The infant was a little fussy one night, got a propranolol dose the next morning, and 2 hours later was pale, cold, clammy, and unresponsive. After resuscitation at a hospital, the child was reported to be doing well.

Photo courtesy Dr. Katherine B. Puttgen

The second case was an 18-month-old with a hemangioma on the nasal tip who had been on a very low dose of propranolol (1.25 mg/kg) for months. Because of a slight respiratory infection, the propranolol was withheld and restarted at a 6 p.m. dosing when the child got better. Thirteen hours later the child was found cold, clammy, and unresponsive. He had a 10-minute seizure and a second seizure on the way to the hospital, where he was found to have a serum glucose of 24 mg/dL. He responded to resuscitation.

In the third case, another child with a nasal tip hemangioma had been on 2 mg/kg per day of propranolol for 8.5 months. Two and a half hours after a breakfast dose, the child was found limp, pale, and tachypneic, and was taken to a hospital, where respiratory syncytial virus infection was diagnosed.

It's not clear what precipitated these crises, Dr. Eichenfield said. And not much is known about how best to use the drug for hemangiomas or how it works for this indication. Even in children whose hemangiomas do not respond to corticosteroids, propranolol often can produce "an incredible clinical response," he said. "You really get them down to essentially nothing very early on. We're quite pleased with those results."

Propranolol has a long history of use in children with heart disease, but not for hemangiomas.

Some physicians admit children who are initiating propranolol for hemangioma treatment, others treat on an outpatient basis. At Dr. Eichenfield's institution, they admit children who are starting the drug in the first 3 months of life, but treat others as outpatients.

The conventional dose is 2-3 mg/kg per day, but it's unclear if there's a dose response, and if patients may do better on 3 mg/kg per day than on the lower dose. Probably half of physicians prescribe a t.i.d. dosage, and others use b.i.d., he said.

It's unclear how long treatment is needed, but "there’s no question that we can get a rebound with propranolol" if the drug is stopped, he said.

Physicians who treat hemangiomas with propranolol should have a clear protocol, Dr. Eichenfield advised. "We'll share our written protocol" with physicians who request it, he said. Dermatologists should collaborate with a pediatrician and possibly a cardiologist on these cases, he added. Written materials for the patients' families and pediatricians can be helpful.

An international, multicenter collaborative study of propranolol for hemangiomas is underway.

Topical beta-blockers also have been considered for hemangiomas. Preliminary data suggest they may produce a response in superficial, flat lesions. But topical beta-blockers also can have systemic side effects. Will they benefit infants with hemangiomas and be safe? "I don’t know. It's a good idea. We’ll see," he said.

Disclosures: Dr. Eichenfield said he has no pertinent conflicts of interest. A member of his division at the university is the primary investigator in a study of propranolol for hemangiomas.

PASADENA, CALIF. - Recent enthusiasm for treating hemangiomas with propranolol has been tempered by reports of life-threatening events in three infants.

"We're wrestling with the propranolol issue in our practice now. There has to be a significant amount of counseling" of patients and their families while clinicians figure out the safest protocols for propranolol use, Dr. Lawrence F. Eichenfield said at the meeting.

The propranolol-for-hemangiomas story started several years ago when French physicians prescribed high-dose prednisolone for severe hemangiomas in four infants, noticed they were developing high blood pressure secondary to the corticosteroid, and put them on a beta-blocker for the high blood pressure. After a few days of beta-blocker therapy, the hemangiomas started disappearing at a much faster rate than they had on the corticosteroid alone.

The physicians then went directly to propranolol therapy for severe hemangiomas in seven more infants, bypassing the corticosteroid. On a dose of 2-3 mg/kg per day, "they saw a similar incredible response to their hemangiomas," with softening and change in color from red to purple noted in all infants at 24 hours, Dr. Eichenfield said (N. Engl. J. Med. 2008;358:2649-51).

The French series expanded to 32 children with severe hemangiomas at a mean age of 4 months, and therapeutic effects were seen in all cases, with a mean treatment duration of 6 months (Pediatrics 2009;124:e423-31).

Photo courtesy Dr. Katherine B. Puttgen

"Now, there are at least 50 articles in the literature in the past 9 months about propranolol, as it expands from the pediatric dermatology hands to others around the world," said Dr. Eichenfield, director of pediatric and adolescent dermatology at Rady Children's Hospital, San Diego. "It’s an incredible drug, but not without its issues."

The most alarming issues appear to be idiosyncratic events with hypotension, hypoglycemia, hypothermia, bradycardia, or asthma exacerbation. Three children developed life-threatening reactions (Arch. Dermatol. 2010;146:775-8).

The first case was an 11-month-old with a periocular hemangioma who titrated up on propranolol dosing for 2 weeks and had been on a stable dose of propranolol for 3 weeks. The infant was a little fussy one night, got a propranolol dose the next morning, and 2 hours later was pale, cold, clammy, and unresponsive. After resuscitation at a hospital, the child was reported to be doing well.

Photo courtesy Dr. Katherine B. Puttgen

The second case was an 18-month-old with a hemangioma on the nasal tip who had been on a very low dose of propranolol (1.25 mg/kg) for months. Because of a slight respiratory infection, the propranolol was withheld and restarted at a 6 p.m. dosing when the child got better. Thirteen hours later the child was found cold, clammy, and unresponsive. He had a 10-minute seizure and a second seizure on the way to the hospital, where he was found to have a serum glucose of 24 mg/dL. He responded to resuscitation.

In the third case, another child with a nasal tip hemangioma had been on 2 mg/kg per day of propranolol for 8.5 months. Two and a half hours after a breakfast dose, the child was found limp, pale, and tachypneic, and was taken to a hospital, where respiratory syncytial virus infection was diagnosed.

It's not clear what precipitated these crises, Dr. Eichenfield said. And not much is known about how best to use the drug for hemangiomas or how it works for this indication. Even in children whose hemangiomas do not respond to corticosteroids, propranolol often can produce "an incredible clinical response," he said. "You really get them down to essentially nothing very early on. We're quite pleased with those results."

Propranolol has a long history of use in children with heart disease, but not for hemangiomas.

Some physicians admit children who are initiating propranolol for hemangioma treatment, others treat on an outpatient basis. At Dr. Eichenfield's institution, they admit children who are starting the drug in the first 3 months of life, but treat others as outpatients.

The conventional dose is 2-3 mg/kg per day, but it's unclear if there's a dose response, and if patients may do better on 3 mg/kg per day than on the lower dose. Probably half of physicians prescribe a t.i.d. dosage, and others use b.i.d., he said.

It's unclear how long treatment is needed, but "there’s no question that we can get a rebound with propranolol" if the drug is stopped, he said.

Physicians who treat hemangiomas with propranolol should have a clear protocol, Dr. Eichenfield advised. "We'll share our written protocol" with physicians who request it, he said. Dermatologists should collaborate with a pediatrician and possibly a cardiologist on these cases, he added. Written materials for the patients' families and pediatricians can be helpful.

An international, multicenter collaborative study of propranolol for hemangiomas is underway.

Topical beta-blockers also have been considered for hemangiomas. Preliminary data suggest they may produce a response in superficial, flat lesions. But topical beta-blockers also can have systemic side effects. Will they benefit infants with hemangiomas and be safe? "I don’t know. It's a good idea. We’ll see," he said.

Disclosures: Dr. Eichenfield said he has no pertinent conflicts of interest. A member of his division at the university is the primary investigator in a study of propranolol for hemangiomas.

SAN FRANCISCO – Early routine MRI helped with the diagnosis of spontaneous intracerebral hemorrhage when added to CT imaging in a prospective, blinded study of 157 patients.

Previous analyses had suggested that adding MRI to brain CT imaging increased correct diagnoses of the cause of spontaneous intracerebral hemorrhage (ICH) by 26% and changed management in 15% of cases, but these percentages were based on the treating physician’s view, not independent neurologists, Dr. Christine A.C. Wijman noted.

The current study, called the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, supports those results. Two independent neuroradiologists found an absolute additive diagnostic benefit of 35% when MRI was added to CT imaging for diagnosing the etiology of ICH or intraventricular hemorrhage (IVH), Dr. Wijman said at the annual meeting of the Neurocritical Care Society.

Consecutive, prospectively enrolled patients underwent brain CT imaging, laboratory testing, and gadolinium-enhanced MRI or a magnetic resonance angiogram (MRA). If they met prespecified criteria, they underwent catheter angiography.

The cohort had a mean age of 63 years and 45% were female. Seventy-one percent had a history of hypertension, and 69% were on an antihypertensive drug at the time of admission.

Their intracranial hemorrhages had a mean initial volume of 25 cc, and associated IVH was present in 43%. The ICH location was lobar in 45% of cases and deep in 38%. The mean Glasgow Coma Score on admission was 14.

The study excluded patients with a known preexisting cause of ICH, an inability to undergo MRI, or a Glasgow Coma Scale score less than 6 on admission.

Initially, two independent neuroradiologists reviewed the admission CT and assigned a presumed cause of the ICH or IVH to 1 of 12 categories, rating the cause as “possible,” “likely,” or “highly probable.” They were blinded to all clinical data other than the patient’s age and sex. Next, two separate independent, blinded neuroradiologists used the first available MRI plus the CT results to do similar evaluations.

Their diagnoses were compared with determination of the etiology at 3 months by a stroke neurologist after review of the medical record including a 90-day clinic visit and follow-up MRI, if those were available.

The added information from the MRI changed the diagnosis of etiology in 24% of cases and improved diagnostic confidence in 11% of cases in which the identified cause did not change, for a combined “additive yield” of 35%, reported Dr. Wijman, director of critical care neurology at Stanford (Calif.) University.

The final diagnoses determined the cause of ICH or IVH to be longstanding or acute hypertension in 42% of cases, cerebral myeloid angioplasty in 15%, vascular malformation in 10%, infarct with hemorrhagic transformation in 8%, other diagnoses in 16%, and unknown causes in 8%. (Percentages do not equal 100% because of rounding.)

CT alone captured the final diagnosis in only 3% of patients. MRI or MRA alone captured the final diagnosis in 24%. Use of information from both imaging modalities captured the final diagnosis in 43%, and neither modality identified the etiology in 31%, Dr. Wijman said. (Percentages exceed 100% because of rounding.)

The MRI information changed the diagnosis of etiology in 10 (15%) of 66 cases of hypertension-related ICH and in 9 (38%) of 24 cases involving cerebral amyloid angiopathy or a variant of this disorder. The MRI information improved confidence in an unchanged diagnosis in eight of the hypertension-related cases (12%) and in five of the cerebral amyloid angiopathy cases (21%).

The additive yield of MRI was relatively highest for cases involving cerebral amyloid angiopathy, vascular malformations, hypertension, and other specific causes.

MRI or MRA proved helpful even in cases where it might be expected to be least useful. For example, the MRI/MRA results changed the diagnosis in 6 (13%) of 46 patients aged older than 45 years who had longstanding hypertension and a deep ICH, she added. It improved the diagnostic confidence in three of those cases (7%), for an overall diagnostic yield of 20%.

Disclosures: Dr. Wijman said the investigators have no pertinent conflicts of interest.

SAN FRANCISCO – Early routine MRI helped with the diagnosis of spontaneous intracerebral hemorrhage when added to CT imaging in a prospective, blinded study of 157 patients.

Previous analyses had suggested that adding MRI to brain CT imaging increased correct diagnoses of the cause of spontaneous intracerebral hemorrhage (ICH) by 26% and changed management in 15% of cases, but these percentages were based on the treating physician’s view, not independent neurologists, Dr. Christine A.C. Wijman noted.

The current study, called the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, supports those results. Two independent neuroradiologists found an absolute additive diagnostic benefit of 35% when MRI was added to CT imaging for diagnosing the etiology of ICH or intraventricular hemorrhage (IVH), Dr. Wijman said at the annual meeting of the Neurocritical Care Society.

Consecutive, prospectively enrolled patients underwent brain CT imaging, laboratory testing, and gadolinium-enhanced MRI or a magnetic resonance angiogram (MRA). If they met prespecified criteria, they underwent catheter angiography.

The cohort had a mean age of 63 years and 45% were female. Seventy-one percent had a history of hypertension, and 69% were on an antihypertensive drug at the time of admission.

Their intracranial hemorrhages had a mean initial volume of 25 cc, and associated IVH was present in 43%. The ICH location was lobar in 45% of cases and deep in 38%. The mean Glasgow Coma Score on admission was 14.

The study excluded patients with a known preexisting cause of ICH, an inability to undergo MRI, or a Glasgow Coma Scale score less than 6 on admission.

Initially, two independent neuroradiologists reviewed the admission CT and assigned a presumed cause of the ICH or IVH to 1 of 12 categories, rating the cause as “possible,” “likely,” or “highly probable.” They were blinded to all clinical data other than the patient’s age and sex. Next, two separate independent, blinded neuroradiologists used the first available MRI plus the CT results to do similar evaluations.

Their diagnoses were compared with determination of the etiology at 3 months by a stroke neurologist after review of the medical record including a 90-day clinic visit and follow-up MRI, if those were available.

The added information from the MRI changed the diagnosis of etiology in 24% of cases and improved diagnostic confidence in 11% of cases in which the identified cause did not change, for a combined “additive yield” of 35%, reported Dr. Wijman, director of critical care neurology at Stanford (Calif.) University.

The final diagnoses determined the cause of ICH or IVH to be longstanding or acute hypertension in 42% of cases, cerebral myeloid angioplasty in 15%, vascular malformation in 10%, infarct with hemorrhagic transformation in 8%, other diagnoses in 16%, and unknown causes in 8%. (Percentages do not equal 100% because of rounding.)

CT alone captured the final diagnosis in only 3% of patients. MRI or MRA alone captured the final diagnosis in 24%. Use of information from both imaging modalities captured the final diagnosis in 43%, and neither modality identified the etiology in 31%, Dr. Wijman said. (Percentages exceed 100% because of rounding.)

The MRI information changed the diagnosis of etiology in 10 (15%) of 66 cases of hypertension-related ICH and in 9 (38%) of 24 cases involving cerebral amyloid angiopathy or a variant of this disorder. The MRI information improved confidence in an unchanged diagnosis in eight of the hypertension-related cases (12%) and in five of the cerebral amyloid angiopathy cases (21%).

The additive yield of MRI was relatively highest for cases involving cerebral amyloid angiopathy, vascular malformations, hypertension, and other specific causes.

MRI or MRA proved helpful even in cases where it might be expected to be least useful. For example, the MRI/MRA results changed the diagnosis in 6 (13%) of 46 patients aged older than 45 years who had longstanding hypertension and a deep ICH, she added. It improved the diagnostic confidence in three of those cases (7%), for an overall diagnostic yield of 20%.

Disclosures: Dr. Wijman said the investigators have no pertinent conflicts of interest.

SAN FRANCISCO – Early routine MRI helped with the diagnosis of spontaneous intracerebral hemorrhage when added to CT imaging in a prospective, blinded study of 157 patients.

Previous analyses had suggested that adding MRI to brain CT imaging increased correct diagnoses of the cause of spontaneous intracerebral hemorrhage (ICH) by 26% and changed management in 15% of cases, but these percentages were based on the treating physician’s view, not independent neurologists, Dr. Christine A.C. Wijman noted.

The current study, called the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, supports those results. Two independent neuroradiologists found an absolute additive diagnostic benefit of 35% when MRI was added to CT imaging for diagnosing the etiology of ICH or intraventricular hemorrhage (IVH), Dr. Wijman said at the annual meeting of the Neurocritical Care Society.

Consecutive, prospectively enrolled patients underwent brain CT imaging, laboratory testing, and gadolinium-enhanced MRI or a magnetic resonance angiogram (MRA). If they met prespecified criteria, they underwent catheter angiography.

The cohort had a mean age of 63 years and 45% were female. Seventy-one percent had a history of hypertension, and 69% were on an antihypertensive drug at the time of admission.

Their intracranial hemorrhages had a mean initial volume of 25 cc, and associated IVH was present in 43%. The ICH location was lobar in 45% of cases and deep in 38%. The mean Glasgow Coma Score on admission was 14.

The study excluded patients with a known preexisting cause of ICH, an inability to undergo MRI, or a Glasgow Coma Scale score less than 6 on admission.

Initially, two independent neuroradiologists reviewed the admission CT and assigned a presumed cause of the ICH or IVH to 1 of 12 categories, rating the cause as “possible,” “likely,” or “highly probable.” They were blinded to all clinical data other than the patient’s age and sex. Next, two separate independent, blinded neuroradiologists used the first available MRI plus the CT results to do similar evaluations.

Their diagnoses were compared with determination of the etiology at 3 months by a stroke neurologist after review of the medical record including a 90-day clinic visit and follow-up MRI, if those were available.

The added information from the MRI changed the diagnosis of etiology in 24% of cases and improved diagnostic confidence in 11% of cases in which the identified cause did not change, for a combined “additive yield” of 35%, reported Dr. Wijman, director of critical care neurology at Stanford (Calif.) University.

The final diagnoses determined the cause of ICH or IVH to be longstanding or acute hypertension in 42% of cases, cerebral myeloid angioplasty in 15%, vascular malformation in 10%, infarct with hemorrhagic transformation in 8%, other diagnoses in 16%, and unknown causes in 8%. (Percentages do not equal 100% because of rounding.)

CT alone captured the final diagnosis in only 3% of patients. MRI or MRA alone captured the final diagnosis in 24%. Use of information from both imaging modalities captured the final diagnosis in 43%, and neither modality identified the etiology in 31%, Dr. Wijman said. (Percentages exceed 100% because of rounding.)

The MRI information changed the diagnosis of etiology in 10 (15%) of 66 cases of hypertension-related ICH and in 9 (38%) of 24 cases involving cerebral amyloid angiopathy or a variant of this disorder. The MRI information improved confidence in an unchanged diagnosis in eight of the hypertension-related cases (12%) and in five of the cerebral amyloid angiopathy cases (21%).

The additive yield of MRI was relatively highest for cases involving cerebral amyloid angiopathy, vascular malformations, hypertension, and other specific causes.

MRI or MRA proved helpful even in cases where it might be expected to be least useful. For example, the MRI/MRA results changed the diagnosis in 6 (13%) of 46 patients aged older than 45 years who had longstanding hypertension and a deep ICH, she added. It improved the diagnostic confidence in three of those cases (7%), for an overall diagnostic yield of 20%.

Disclosures: Dr. Wijman said the investigators have no pertinent conflicts of interest.

SAN FRANCISCO – Early routine MRI helped with the diagnosis of spontaneous intracerebral hemorrhage when added to CT imaging in a prospective, blinded study of 157 patients.

Previous analyses had suggested that adding MRI to brain CT imaging increased correct diagnoses of the cause of spontaneous intracerebral hemorrhage (ICH) by 26% and changed management in 15% of cases, but these percentages were based on the treating physician’s view, not independent neurologists, Dr. Christine A.C. Wijman noted.

The current study, called the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, supports those results. Two independent neuroradiologists found an absolute additive diagnostic benefit of 35% when MRI was added to CT imaging for diagnosing the etiology of ICH or intraventricular hemorrhage (IVH), Dr. Wijman said at the annual meeting of the Neurocritical Care Society.

Consecutive, prospectively enrolled patients underwent brain CT imaging, laboratory testing, and gadolinium-enhanced MRI or a magnetic resonance angiogram (MRA). If they met prespecified criteria, they underwent catheter angiography.

The cohort had a mean age of 63 years and 45% were female. Seventy-one percent had a history of hypertension, and 69% were on an antihypertensive drug at the time of admission.

Their intracranial hemorrhages had a mean initial volume of 25 cc, and associated IVH was present in 43%. The ICH location was lobar in 45% of cases and deep in 38%. The mean Glasgow Coma Score on admission was 14.

The study excluded patients with a known preexisting cause of ICH, an inability to undergo MRI, or a Glasgow Coma Scale score less than 6 on admission.

Initially, two independent neuroradiologists reviewed the admission CT and assigned a presumed cause of the ICH or IVH to 1 of 12 categories, rating the cause as “possible,” “likely,” or “highly probable.” They were blinded to all clinical data other than the patient’s age and sex. Next, two separate independent, blinded neuroradiologists used the first available MRI plus the CT results to do similar evaluations.

Their diagnoses were compared with determination of the etiology at 3 months by a stroke neurologist after review of the medical record including a 90-day clinic visit and follow-up MRI, if those were available.

The added information from the MRI changed the diagnosis of etiology in 24% of cases and improved diagnostic confidence in 11% of cases in which the identified cause did not change, for a combined “additive yield” of 35%, reported Dr. Wijman, director of critical care neurology at Stanford (Calif.) University.

The final diagnoses determined the cause of ICH or IVH to be longstanding or acute hypertension in 42% of cases, cerebral myeloid angioplasty in 15%, vascular malformation in 10%, infarct with hemorrhagic transformation in 8%, other diagnoses in 16%, and unknown causes in 8%. (Percentages do not equal 100% because of rounding.)

CT alone captured the final diagnosis in only 3% of patients. MRI or MRA alone captured the final diagnosis in 24%. Use of information from both imaging modalities captured the final diagnosis in 43%, and neither modality identified the etiology in 31%, Dr. Wijman said. (Percentages exceed 100% because of rounding.)

The MRI information changed the diagnosis of etiology in 10 (15%) of 66 cases of hypertension-related ICH and in 9 (38%) of 24 cases involving cerebral amyloid angiopathy or a variant of this disorder. The MRI information improved confidence in an unchanged diagnosis in eight of the hypertension-related cases (12%) and in five of the cerebral amyloid angiopathy cases (21%).

The additive yield of MRI was relatively highest for cases involving cerebral amyloid angiopathy, vascular malformations, hypertension, and other specific causes.

MRI or MRA proved helpful even in cases where it might be expected to be least useful. For example, the MRI/MRA results changed the diagnosis in 6 (13%) of 46 patients aged older than 45 years who had longstanding hypertension and a deep ICH, she added. It improved the diagnostic confidence in three of those cases (7%), for an overall diagnostic yield of 20%.

Disclosures: Dr. Wijman said the investigators have no pertinent conflicts of interest.

SAN FRANCISCO – Early routine MRI helped with the diagnosis of spontaneous intracerebral hemorrhage when added to CT imaging in a prospective, blinded study of 157 patients.

Previous analyses had suggested that adding MRI to brain CT imaging increased correct diagnoses of the cause of spontaneous intracerebral hemorrhage (ICH) by 26% and changed management in 15% of cases, but these percentages were based on the treating physician’s view, not independent neurologists, Dr. Christine A.C. Wijman noted.

The current study, called the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, supports those results. Two independent neuroradiologists found an absolute additive diagnostic benefit of 35% when MRI was added to CT imaging for diagnosing the etiology of ICH or intraventricular hemorrhage (IVH), Dr. Wijman said at the annual meeting of the Neurocritical Care Society.

Consecutive, prospectively enrolled patients underwent brain CT imaging, laboratory testing, and gadolinium-enhanced MRI or a magnetic resonance angiogram (MRA). If they met prespecified criteria, they underwent catheter angiography.

The cohort had a mean age of 63 years and 45% were female. Seventy-one percent had a history of hypertension, and 69% were on an antihypertensive drug at the time of admission.

Their intracranial hemorrhages had a mean initial volume of 25 cc, and associated IVH was present in 43%. The ICH location was lobar in 45% of cases and deep in 38%. The mean Glasgow Coma Score on admission was 14.

The study excluded patients with a known preexisting cause of ICH, an inability to undergo MRI, or a Glasgow Coma Scale score less than 6 on admission.

Initially, two independent neuroradiologists reviewed the admission CT and assigned a presumed cause of the ICH or IVH to 1 of 12 categories, rating the cause as “possible,” “likely,” or “highly probable.” They were blinded to all clinical data other than the patient’s age and sex. Next, two separate independent, blinded neuroradiologists used the first available MRI plus the CT results to do similar evaluations.

Their diagnoses were compared with determination of the etiology at 3 months by a stroke neurologist after review of the medical record including a 90-day clinic visit and follow-up MRI, if those were available.

The added information from the MRI changed the diagnosis of etiology in 24% of cases and improved diagnostic confidence in 11% of cases in which the identified cause did not change, for a combined “additive yield” of 35%, reported Dr. Wijman, director of critical care neurology at Stanford (Calif.) University.

The final diagnoses determined the cause of ICH or IVH to be longstanding or acute hypertension in 42% of cases, cerebral myeloid angioplasty in 15%, vascular malformation in 10%, infarct with hemorrhagic transformation in 8%, other diagnoses in 16%, and unknown causes in 8%. (Percentages do not equal 100% because of rounding.)

CT alone captured the final diagnosis in only 3% of patients. MRI or MRA alone captured the final diagnosis in 24%. Use of information from both imaging modalities captured the final diagnosis in 43%, and neither modality identified the etiology in 31%, Dr. Wijman said. (Percentages exceed 100% because of rounding.)

The MRI information changed the diagnosis of etiology in 10 (15%) of 66 cases of hypertension-related ICH and in 9 (38%) of 24 cases involving cerebral amyloid angiopathy or a variant of this disorder. The MRI information improved confidence in an unchanged diagnosis in eight of the hypertension-related cases (12%) and in five of the cerebral amyloid angiopathy cases (21%).

The additive yield of MRI was relatively highest for cases involving cerebral amyloid angiopathy, vascular malformations, hypertension, and other specific causes.

MRI or MRA proved helpful even in cases where it might be expected to be least useful. For example, the MRI/MRA results changed the diagnosis in 6 (13%) of 46 patients aged older than 45 years who had longstanding hypertension and a deep ICH, she added. It improved the diagnostic confidence in three of those cases (7%), for an overall diagnostic yield of 20%.

Disclosures: Dr. Wijman said the investigators have no pertinent conflicts of interest.

SAN FRANCISCO – Early routine MRI helped with the diagnosis of spontaneous intracerebral hemorrhage when added to CT imaging in a prospective, blinded study of 157 patients.

Previous analyses had suggested that adding MRI to brain CT imaging increased correct diagnoses of the cause of spontaneous intracerebral hemorrhage (ICH) by 26% and changed management in 15% of cases, but these percentages were based on the treating physician’s view, not independent neurologists, Dr. Christine A.C. Wijman noted.

The current study, called the Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, supports those results. Two independent neuroradiologists found an absolute additive diagnostic benefit of 35% when MRI was added to CT imaging for diagnosing the etiology of ICH or intraventricular hemorrhage (IVH), Dr. Wijman said at the annual meeting of the Neurocritical Care Society.

Consecutive, prospectively enrolled patients underwent brain CT imaging, laboratory testing, and gadolinium-enhanced MRI or a magnetic resonance angiogram (MRA). If they met prespecified criteria, they underwent catheter angiography.

The cohort had a mean age of 63 years and 45% were female. Seventy-one percent had a history of hypertension, and 69% were on an antihypertensive drug at the time of admission.

Their intracranial hemorrhages had a mean initial volume of 25 cc, and associated IVH was present in 43%. The ICH location was lobar in 45% of cases and deep in 38%. The mean Glasgow Coma Score on admission was 14.

The study excluded patients with a known preexisting cause of ICH, an inability to undergo MRI, or a Glasgow Coma Scale score less than 6 on admission.

Initially, two independent neuroradiologists reviewed the admission CT and assigned a presumed cause of the ICH or IVH to 1 of 12 categories, rating the cause as “possible,” “likely,” or “highly probable.” They were blinded to all clinical data other than the patient’s age and sex. Next, two separate independent, blinded neuroradiologists used the first available MRI plus the CT results to do similar evaluations.

Their diagnoses were compared with determination of the etiology at 3 months by a stroke neurologist after review of the medical record including a 90-day clinic visit and follow-up MRI, if those were available.

The added information from the MRI changed the diagnosis of etiology in 24% of cases and improved diagnostic confidence in 11% of cases in which the identified cause did not change, for a combined “additive yield” of 35%, reported Dr. Wijman, director of critical care neurology at Stanford (Calif.) University.

The final diagnoses determined the cause of ICH or IVH to be longstanding or acute hypertension in 42% of cases, cerebral myeloid angioplasty in 15%, vascular malformation in 10%, infarct with hemorrhagic transformation in 8%, other diagnoses in 16%, and unknown causes in 8%. (Percentages do not equal 100% because of rounding.)

CT alone captured the final diagnosis in only 3% of patients. MRI or MRA alone captured the final diagnosis in 24%. Use of information from both imaging modalities captured the final diagnosis in 43%, and neither modality identified the etiology in 31%, Dr. Wijman said. (Percentages exceed 100% because of rounding.)

The MRI information changed the diagnosis of etiology in 10 (15%) of 66 cases of hypertension-related ICH and in 9 (38%) of 24 cases involving cerebral amyloid angiopathy or a variant of this disorder. The MRI information improved confidence in an unchanged diagnosis in eight of the hypertension-related cases (12%) and in five of the cerebral amyloid angiopathy cases (21%).

The additive yield of MRI was relatively highest for cases involving cerebral amyloid angiopathy, vascular malformations, hypertension, and other specific causes.

MRI or MRA proved helpful even in cases where it might be expected to be least useful. For example, the MRI/MRA results changed the diagnosis in 6 (13%) of 46 patients aged older than 45 years who had longstanding hypertension and a deep ICH, she added. It improved the diagnostic confidence in three of those cases (7%), for an overall diagnostic yield of 20%.

Disclosures: Dr. Wijman said the investigators have no pertinent conflicts of interest.

LOS ANGELES - An experimental inhaled form of dihydroergotamine appears to be effective in reducing migraine pain even if taken as late as 8 hours or more after the start of the headache, a post hoc analysis of a phase III clinical trial suggests.

Investigators analyzed data from the randomized, double-blind, placebo-controlled trial known as the FREEDOM 301 study. Among 771 patients who treated a moderate to severe migraine and recorded both efficacy and the time from onset of headache to treatment, patients randomized to inhaled dihydroergotamine were significantly more likely than those given placebo to report being pain-free 2 hours after treatment if they initiated treatment within an hour of migraine onset, 1-4 hours after onset, or 4-8 hours after migraine onset, Dr. Stewart J. Tepper and his associates reported at the annual meeting of the American Headache Society.

Rates of freedom from pain were not significantly higher with the drug, compared with placebo in patients who took treatment more than 8 hours after the migraine started. Reports of pain relief, however, were significantly higher in the inhaled dihydroergotamine subgroups regardless of how long after headache onset they took treatment, he said at the meeting.

In the real world, patients give a number of reasons for delaying treatment for migraines, noted Dr. Tepper of the Cleveland Clinic. Some want to be sure they have a migraine, or that they need triptan therapy. Some patients hoard medicine for cost reasons. Others just don’t want to take a strong medicine if it’s not needed. Triptan drugs are known to provide their best relief when taken early in a migraine attack and to have reduced efficacy when treatment is delayed, he said. Inhaled dihydroergotamine may offer an alternative for patients who delay starting migraine treatment, if the formulation wins approval, he added.

Freedom from pain at 2 hours after treatment was reported by 34% of 112 patients randomized to inhaled dihydroergotamine and 11% of 118 on placebo who took treatment within an hour of headache onset. In those who took treatment after an hour but within 4 hours of migraine onset, 18% of 152 patients on inhaled dihydroergotamine and 6% of 169 on placebo were pain free 2 hours later. Among patients who treated their migraine after 4 hours but within 8 hours of onset, 22 of 68 (32%) on inhaled dihydroergotamine and 8 of 53 (15%) on placebo were pain free 2 hours later.

For patients who started treatment more than 8 hours after migraine onset, 19 of 53 (36%) on inhaled dihydroergotamine and 9 of 46 (20%) on placebo were pain free 2 hours later. Although those rates were not significantly different, pain relief 2 hours after treatment was reported by 49 on inhaled dihydroergotamine (92%) and 24 on placebo (52%), a significant difference between groups.

“That’s a very dramatic finding,” Dr. Tepper said.

Pain relief rates in patients who started treatment within an hour of migraine onset were 60% with inhaled dihydroergotamine and 35% with placebo. Among those who started treatment after an hour but within 4 hours of migraine onset, 37% on inhaled dihydroergotamine and 21% on placebo reported pain relief 2 hours later. Pain relief also occurred in 53 patients on inhaled dihydroergotamine (78%) and 30 on placebo (57%) who took treatment after 4 hours but within 8 hours of migraine onset.

Data on adverse events in 404 patients in the inhaled dihydroergotamine group and 401 in the placebo group suggest that the drug is well tolerated, Dr. Tepper said. Symptoms typically associated with triptan use, such as chest discomfort or chest pain, occurred rarely and at similar rates in both groups. There were no drug-related serious adverse events and no clinically meaningful change in lung function in this single-dose study. The most common adverse events that occurred more often with inhaled dihydroergotamine than with placebo were bad taste (in 6% and 2%, respectively), nausea (in 4% and 2%, respectively), and cough or vomiting (both in 2% and 1%, respectively).

The main FREEDOM 301 trial included 792 patients in an intent-to-treat analysis, and showed significantly increased likelihood of pain relief 2 hours after treatment in all patients on inhaled dihydroergotamine (59%), compared with patients on placebo (35%). Pain relief rates were significantly different between groups within an hour of treatment and remained significantly different after 24 and 48 hours.

Dihydroergotamine traditionally has been used in both an oral form and as an infusion for migraine. The inhaled version may work more quickly by passing directly into the bloodstream through the lungs.

“I can think of many clinical situations where this will be useful,” he said. “We hope this device will be able to be used at home.”

LOS ANGELES - An experimental inhaled form of dihydroergotamine appears to be effective in reducing migraine pain even if taken as late as 8 hours or more after the start of the headache, a post hoc analysis of a phase III clinical trial suggests.

Investigators analyzed data from the randomized, double-blind, placebo-controlled trial known as the FREEDOM 301 study. Among 771 patients who treated a moderate to severe migraine and recorded both efficacy and the time from onset of headache to treatment, patients randomized to inhaled dihydroergotamine were significantly more likely than those given placebo to report being pain-free 2 hours after treatment if they initiated treatment within an hour of migraine onset, 1-4 hours after onset, or 4-8 hours after migraine onset, Dr. Stewart J. Tepper and his associates reported at the annual meeting of the American Headache Society.

Rates of freedom from pain were not significantly higher with the drug, compared with placebo in patients who took treatment more than 8 hours after the migraine started. Reports of pain relief, however, were significantly higher in the inhaled dihydroergotamine subgroups regardless of how long after headache onset they took treatment, he said at the meeting.

In the real world, patients give a number of reasons for delaying treatment for migraines, noted Dr. Tepper of the Cleveland Clinic. Some want to be sure they have a migraine, or that they need triptan therapy. Some patients hoard medicine for cost reasons. Others just don’t want to take a strong medicine if it’s not needed. Triptan drugs are known to provide their best relief when taken early in a migraine attack and to have reduced efficacy when treatment is delayed, he said. Inhaled dihydroergotamine may offer an alternative for patients who delay starting migraine treatment, if the formulation wins approval, he added.

Freedom from pain at 2 hours after treatment was reported by 34% of 112 patients randomized to inhaled dihydroergotamine and 11% of 118 on placebo who took treatment within an hour of headache onset. In those who took treatment after an hour but within 4 hours of migraine onset, 18% of 152 patients on inhaled dihydroergotamine and 6% of 169 on placebo were pain free 2 hours later. Among patients who treated their migraine after 4 hours but within 8 hours of onset, 22 of 68 (32%) on inhaled dihydroergotamine and 8 of 53 (15%) on placebo were pain free 2 hours later.

For patients who started treatment more than 8 hours after migraine onset, 19 of 53 (36%) on inhaled dihydroergotamine and 9 of 46 (20%) on placebo were pain free 2 hours later. Although those rates were not significantly different, pain relief 2 hours after treatment was reported by 49 on inhaled dihydroergotamine (92%) and 24 on placebo (52%), a significant difference between groups.

“That’s a very dramatic finding,” Dr. Tepper said.

Pain relief rates in patients who started treatment within an hour of migraine onset were 60% with inhaled dihydroergotamine and 35% with placebo. Among those who started treatment after an hour but within 4 hours of migraine onset, 37% on inhaled dihydroergotamine and 21% on placebo reported pain relief 2 hours later. Pain relief also occurred in 53 patients on inhaled dihydroergotamine (78%) and 30 on placebo (57%) who took treatment after 4 hours but within 8 hours of migraine onset.

Data on adverse events in 404 patients in the inhaled dihydroergotamine group and 401 in the placebo group suggest that the drug is well tolerated, Dr. Tepper said. Symptoms typically associated with triptan use, such as chest discomfort or chest pain, occurred rarely and at similar rates in both groups. There were no drug-related serious adverse events and no clinically meaningful change in lung function in this single-dose study. The most common adverse events that occurred more often with inhaled dihydroergotamine than with placebo were bad taste (in 6% and 2%, respectively), nausea (in 4% and 2%, respectively), and cough or vomiting (both in 2% and 1%, respectively).

The main FREEDOM 301 trial included 792 patients in an intent-to-treat analysis, and showed significantly increased likelihood of pain relief 2 hours after treatment in all patients on inhaled dihydroergotamine (59%), compared with patients on placebo (35%). Pain relief rates were significantly different between groups within an hour of treatment and remained significantly different after 24 and 48 hours.

Dihydroergotamine traditionally has been used in both an oral form and as an infusion for migraine. The inhaled version may work more quickly by passing directly into the bloodstream through the lungs.

“I can think of many clinical situations where this will be useful,” he said. “We hope this device will be able to be used at home.”

LOS ANGELES - An experimental inhaled form of dihydroergotamine appears to be effective in reducing migraine pain even if taken as late as 8 hours or more after the start of the headache, a post hoc analysis of a phase III clinical trial suggests.

Investigators analyzed data from the randomized, double-blind, placebo-controlled trial known as the FREEDOM 301 study. Among 771 patients who treated a moderate to severe migraine and recorded both efficacy and the time from onset of headache to treatment, patients randomized to inhaled dihydroergotamine were significantly more likely than those given placebo to report being pain-free 2 hours after treatment if they initiated treatment within an hour of migraine onset, 1-4 hours after onset, or 4-8 hours after migraine onset, Dr. Stewart J. Tepper and his associates reported at the annual meeting of the American Headache Society.

Rates of freedom from pain were not significantly higher with the drug, compared with placebo in patients who took treatment more than 8 hours after the migraine started. Reports of pain relief, however, were significantly higher in the inhaled dihydroergotamine subgroups regardless of how long after headache onset they took treatment, he said at the meeting.

In the real world, patients give a number of reasons for delaying treatment for migraines, noted Dr. Tepper of the Cleveland Clinic. Some want to be sure they have a migraine, or that they need triptan therapy. Some patients hoard medicine for cost reasons. Others just don’t want to take a strong medicine if it’s not needed. Triptan drugs are known to provide their best relief when taken early in a migraine attack and to have reduced efficacy when treatment is delayed, he said. Inhaled dihydroergotamine may offer an alternative for patients who delay starting migraine treatment, if the formulation wins approval, he added.

Freedom from pain at 2 hours after treatment was reported by 34% of 112 patients randomized to inhaled dihydroergotamine and 11% of 118 on placebo who took treatment within an hour of headache onset. In those who took treatment after an hour but within 4 hours of migraine onset, 18% of 152 patients on inhaled dihydroergotamine and 6% of 169 on placebo were pain free 2 hours later. Among patients who treated their migraine after 4 hours but within 8 hours of onset, 22 of 68 (32%) on inhaled dihydroergotamine and 8 of 53 (15%) on placebo were pain free 2 hours later.

For patients who started treatment more than 8 hours after migraine onset, 19 of 53 (36%) on inhaled dihydroergotamine and 9 of 46 (20%) on placebo were pain free 2 hours later. Although those rates were not significantly different, pain relief 2 hours after treatment was reported by 49 on inhaled dihydroergotamine (92%) and 24 on placebo (52%), a significant difference between groups.

“That’s a very dramatic finding,” Dr. Tepper said.

Pain relief rates in patients who started treatment within an hour of migraine onset were 60% with inhaled dihydroergotamine and 35% with placebo. Among those who started treatment after an hour but within 4 hours of migraine onset, 37% on inhaled dihydroergotamine and 21% on placebo reported pain relief 2 hours later. Pain relief also occurred in 53 patients on inhaled dihydroergotamine (78%) and 30 on placebo (57%) who took treatment after 4 hours but within 8 hours of migraine onset.

Data on adverse events in 404 patients in the inhaled dihydroergotamine group and 401 in the placebo group suggest that the drug is well tolerated, Dr. Tepper said. Symptoms typically associated with triptan use, such as chest discomfort or chest pain, occurred rarely and at similar rates in both groups. There were no drug-related serious adverse events and no clinically meaningful change in lung function in this single-dose study. The most common adverse events that occurred more often with inhaled dihydroergotamine than with placebo were bad taste (in 6% and 2%, respectively), nausea (in 4% and 2%, respectively), and cough or vomiting (both in 2% and 1%, respectively).

The main FREEDOM 301 trial included 792 patients in an intent-to-treat analysis, and showed significantly increased likelihood of pain relief 2 hours after treatment in all patients on inhaled dihydroergotamine (59%), compared with patients on placebo (35%). Pain relief rates were significantly different between groups within an hour of treatment and remained significantly different after 24 and 48 hours.

Dihydroergotamine traditionally has been used in both an oral form and as an infusion for migraine. The inhaled version may work more quickly by passing directly into the bloodstream through the lungs.

“I can think of many clinical situations where this will be useful,” he said. “We hope this device will be able to be used at home.”