Michele G. Sullivan

After a double embryo transfer, women who are 5’7" or taller are twice as likely to carry dizygotic twins as are shorter women.

The incidence of twinning also significantly increased with an increasing number of retrieved oocytes, according to a retrospective database review.

The findings may help reproductive specialists develop a "tailor-made, personalized in vitro fertilization treatment," Dr. Marieke Lambers said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Lambers of Vrije Universiteit Medisch Centrum, Amsterdam, used information from the OMEGA database, a Dutch cohort study of ovarian stimulation for in vitro fertilization (IVF) and subsequent gynecologic diseases. The study comprised 19,840 women who underwent IVF or intracytoplasmic sperm injection from 1983 to 1995. Women received health questionnaires from 1997 to 1999, which were combined with data from their medical records.

Dr. Lambers’s analysis included 2,357 women who completed a first fresh – not cryopreserved – IVF cycle with a double embryo transfer. These resulted in 371 singleton pregnancies and 125 twin pregnancies.

The investigators conducted a multifactorial regression analysis to determine what factors, if any, influenced twinning in the mothers. These included body mass index, weight and height, maternal age, number of retrieved oocytes, alcohol use, education, and parity.

Two factors – maternal height and the number of eggs retrieved – were significantly associated with twinning, Dr. Lambers said. Women taller than 174 cm (5’7") were twice as likely to have twins as were shorter women. Those who had more than 11 oocytes retrieved were 2.4 times more likely to have twins than were those with fewer eggs retrieved.

Since the data were observational, it’s not possible to draw any causal relationships, but Dr. Lambers suggested that the higher number of oocytes could be an indication of egg quality. "The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos," she said.

However, "the association between increased height and pregnancy is more difficult to explain." Vascular endothelial growth factor (VEG-F) could play a part, she suggested. "Previous studies have shown that women who are prone to conceive twins after IVF had a higher level of [the growth factor], which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEG-F levels."

Theory aside, the findings could help refine IVF strategies for both doctors and patients.

"Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births. We hope this work could be used in the future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is important, because multiple pregnancies involved a higher risk of problems for the mother, such as preeclampsia, and also for the baby, [because of] preterm or immature delivery."

Dr. Lambers did not have any relevant financial disclosures.

After a double embryo transfer, women who are 5’7" or taller are twice as likely to carry dizygotic twins as are shorter women.

The incidence of twinning also significantly increased with an increasing number of retrieved oocytes, according to a retrospective database review.

The findings may help reproductive specialists develop a "tailor-made, personalized in vitro fertilization treatment," Dr. Marieke Lambers said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Lambers of Vrije Universiteit Medisch Centrum, Amsterdam, used information from the OMEGA database, a Dutch cohort study of ovarian stimulation for in vitro fertilization (IVF) and subsequent gynecologic diseases. The study comprised 19,840 women who underwent IVF or intracytoplasmic sperm injection from 1983 to 1995. Women received health questionnaires from 1997 to 1999, which were combined with data from their medical records.

Dr. Lambers’s analysis included 2,357 women who completed a first fresh – not cryopreserved – IVF cycle with a double embryo transfer. These resulted in 371 singleton pregnancies and 125 twin pregnancies.

The investigators conducted a multifactorial regression analysis to determine what factors, if any, influenced twinning in the mothers. These included body mass index, weight and height, maternal age, number of retrieved oocytes, alcohol use, education, and parity.

Two factors – maternal height and the number of eggs retrieved – were significantly associated with twinning, Dr. Lambers said. Women taller than 174 cm (5’7") were twice as likely to have twins as were shorter women. Those who had more than 11 oocytes retrieved were 2.4 times more likely to have twins than were those with fewer eggs retrieved.

Since the data were observational, it’s not possible to draw any causal relationships, but Dr. Lambers suggested that the higher number of oocytes could be an indication of egg quality. "The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos," she said.

However, "the association between increased height and pregnancy is more difficult to explain." Vascular endothelial growth factor (VEG-F) could play a part, she suggested. "Previous studies have shown that women who are prone to conceive twins after IVF had a higher level of [the growth factor], which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEG-F levels."

Theory aside, the findings could help refine IVF strategies for both doctors and patients.

"Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births. We hope this work could be used in the future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is important, because multiple pregnancies involved a higher risk of problems for the mother, such as preeclampsia, and also for the baby, [because of] preterm or immature delivery."

Dr. Lambers did not have any relevant financial disclosures.

After a double embryo transfer, women who are 5’7" or taller are twice as likely to carry dizygotic twins as are shorter women.

The incidence of twinning also significantly increased with an increasing number of retrieved oocytes, according to a retrospective database review.

The findings may help reproductive specialists develop a "tailor-made, personalized in vitro fertilization treatment," Dr. Marieke Lambers said during a press briefing at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Lambers of Vrije Universiteit Medisch Centrum, Amsterdam, used information from the OMEGA database, a Dutch cohort study of ovarian stimulation for in vitro fertilization (IVF) and subsequent gynecologic diseases. The study comprised 19,840 women who underwent IVF or intracytoplasmic sperm injection from 1983 to 1995. Women received health questionnaires from 1997 to 1999, which were combined with data from their medical records.

Dr. Lambers’s analysis included 2,357 women who completed a first fresh – not cryopreserved – IVF cycle with a double embryo transfer. These resulted in 371 singleton pregnancies and 125 twin pregnancies.

The investigators conducted a multifactorial regression analysis to determine what factors, if any, influenced twinning in the mothers. These included body mass index, weight and height, maternal age, number of retrieved oocytes, alcohol use, education, and parity.

Two factors – maternal height and the number of eggs retrieved – were significantly associated with twinning, Dr. Lambers said. Women taller than 174 cm (5’7") were twice as likely to have twins as were shorter women. Those who had more than 11 oocytes retrieved were 2.4 times more likely to have twins than were those with fewer eggs retrieved.

Since the data were observational, it’s not possible to draw any causal relationships, but Dr. Lambers suggested that the higher number of oocytes could be an indication of egg quality. "The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos," she said.

However, "the association between increased height and pregnancy is more difficult to explain." Vascular endothelial growth factor (VEG-F) could play a part, she suggested. "Previous studies have shown that women who are prone to conceive twins after IVF had a higher level of [the growth factor], which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEG-F levels."

Theory aside, the findings could help refine IVF strategies for both doctors and patients.

"Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births. We hope this work could be used in the future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is important, because multiple pregnancies involved a higher risk of problems for the mother, such as preeclampsia, and also for the baby, [because of] preterm or immature delivery."

Dr. Lambers did not have any relevant financial disclosures.

Women who experience two or even more unexplained miscarriages are still likely to conceive and carry a child, with about 65% giving birth to a live infant, results of two new studies show.

Most of the successful pregnancies seem to occur within a year or so after a woman sees a fertility specialist, Dr. Ole Christiansen said during a press briefing at the annual meeting of the European Society of Reproduction and Embryology. Success is not related to treatment, since none exists for unexplained miscarriage. Instead, said Dr. Christiansen of Rigshospitalet, Copenhagen, the declining incidence of birth over 5 years is probably related to increasing maternal age with each attempt, or to the decision to give up efforts to conceive.

Dr. Stef P. Kaandorp, whose study came to a similar conclusion, said the results of both are encouraging.

"Women with recurrent miscarriage can be reassured that their time to a subsequent conception is not significantly longer that that for fertile women without a history of miscarriage," said Dr. Kaandorp, a research fellow at the University of Amsterdam. "Recurrent miscarriage is extremely stressful for these women, and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much."

Prof. Christiansen presented a population-based retrospective study conducted in Denmark. Data were extracted from the National Danish Birth registry and identified 987 women who had at least three consecutive miscarriages and had been referred to a specialist clinic between 1986 and 2008. All of these women were aged 20-46 years at the time of referral. About one-third had some prior fertility treatments, including hormones, anticoagulants, and intravenous immunoglobulin.

Overall, 66% of the women (651) achieved a live birth after the consultation, Dr. Christiansen said. The highest rate occurred within the first 15 months of the consultation (71%). "The curve declines very rapidly after the first year after the consultation, then after 5 years it really flattens out," he said. "Only 2%-3% are likely to have a child after that."

Subgroup analyses found that increasing maternal age and the number of prior miscarriages were significantly associated with a continued rate of unsuccessful pregnancy. Nor were prior infertility treatments related to a later live birth, he said.

However, the new data should allow researchers to create a risk estimate graph that can predict the chance of a live birth much more precisely. "Instead of giving these women an uncertain risk estimate [for future live birth], we can now combine their age and number of miscarriages to give them a closer estimate of a live birth, and that is what matters to these women," he said.

Future research on this same cohort may look at what factors the male partner brings to the picture of recurrent miscarriage – if any.

In the second study, Dr. Kaandorp conducted a subanalysis of the ALIFE trial – a randomized, placebo-controlled study that showed neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate among women with unexplained recurrent miscarriage; the study ran from 2004-2008 (N. Engl. J. Med. 2010;362:1586-96).

Of the 364 women enrolled in that trial, Dr. Kaandorp identified 251 who had at least two miscarriages with a gestational age of 20 weeks or less and examined their subsequent rates of conception and live birth.

Of the cohort, 213 became naturally pregnant during by 2009. The median time to conception, regardless of outcome, was 21 weeks, although the range was 8-55 weeks. The cumulative pregnancy rate was 56% after 6 months, 74% after 12 months, and 86% after 24 months.

Of those who did conceive, 139 gave birth to a living child; 69 experienced another miscarriage; 2 had an ectopic pregnancy; 2 terminated the pregnancy; and 1 had an intrauterine death.

The presence of the Factor V Leiden genetic condition was the only factor significantly related to a shorter time to pregnancy; it increased by 91% the chance of conception by 11 weeks, compared with noncarriers.

"We should be cautious with this finding, because it only occurred in 11 women," Dr. Kaandorp noted. "At this point, I think we can only see it as hypothesis generating."

Neither Dr. Christiansen nor Dr. Kaandorp had any financial disclosures.

Women who experience two or even more unexplained miscarriages are still likely to conceive and carry a child, with about 65% giving birth to a live infant, results of two new studies show.

Most of the successful pregnancies seem to occur within a year or so after a woman sees a fertility specialist, Dr. Ole Christiansen said during a press briefing at the annual meeting of the European Society of Reproduction and Embryology. Success is not related to treatment, since none exists for unexplained miscarriage. Instead, said Dr. Christiansen of Rigshospitalet, Copenhagen, the declining incidence of birth over 5 years is probably related to increasing maternal age with each attempt, or to the decision to give up efforts to conceive.

Dr. Stef P. Kaandorp, whose study came to a similar conclusion, said the results of both are encouraging.

"Women with recurrent miscarriage can be reassured that their time to a subsequent conception is not significantly longer that that for fertile women without a history of miscarriage," said Dr. Kaandorp, a research fellow at the University of Amsterdam. "Recurrent miscarriage is extremely stressful for these women, and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much."

Prof. Christiansen presented a population-based retrospective study conducted in Denmark. Data were extracted from the National Danish Birth registry and identified 987 women who had at least three consecutive miscarriages and had been referred to a specialist clinic between 1986 and 2008. All of these women were aged 20-46 years at the time of referral. About one-third had some prior fertility treatments, including hormones, anticoagulants, and intravenous immunoglobulin.

Overall, 66% of the women (651) achieved a live birth after the consultation, Dr. Christiansen said. The highest rate occurred within the first 15 months of the consultation (71%). "The curve declines very rapidly after the first year after the consultation, then after 5 years it really flattens out," he said. "Only 2%-3% are likely to have a child after that."

Subgroup analyses found that increasing maternal age and the number of prior miscarriages were significantly associated with a continued rate of unsuccessful pregnancy. Nor were prior infertility treatments related to a later live birth, he said.

However, the new data should allow researchers to create a risk estimate graph that can predict the chance of a live birth much more precisely. "Instead of giving these women an uncertain risk estimate [for future live birth], we can now combine their age and number of miscarriages to give them a closer estimate of a live birth, and that is what matters to these women," he said.

Future research on this same cohort may look at what factors the male partner brings to the picture of recurrent miscarriage – if any.

In the second study, Dr. Kaandorp conducted a subanalysis of the ALIFE trial – a randomized, placebo-controlled study that showed neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate among women with unexplained recurrent miscarriage; the study ran from 2004-2008 (N. Engl. J. Med. 2010;362:1586-96).

Of the 364 women enrolled in that trial, Dr. Kaandorp identified 251 who had at least two miscarriages with a gestational age of 20 weeks or less and examined their subsequent rates of conception and live birth.

Of the cohort, 213 became naturally pregnant during by 2009. The median time to conception, regardless of outcome, was 21 weeks, although the range was 8-55 weeks. The cumulative pregnancy rate was 56% after 6 months, 74% after 12 months, and 86% after 24 months.

Of those who did conceive, 139 gave birth to a living child; 69 experienced another miscarriage; 2 had an ectopic pregnancy; 2 terminated the pregnancy; and 1 had an intrauterine death.

The presence of the Factor V Leiden genetic condition was the only factor significantly related to a shorter time to pregnancy; it increased by 91% the chance of conception by 11 weeks, compared with noncarriers.

"We should be cautious with this finding, because it only occurred in 11 women," Dr. Kaandorp noted. "At this point, I think we can only see it as hypothesis generating."

Neither Dr. Christiansen nor Dr. Kaandorp had any financial disclosures.

Women who experience two or even more unexplained miscarriages are still likely to conceive and carry a child, with about 65% giving birth to a live infant, results of two new studies show.

Most of the successful pregnancies seem to occur within a year or so after a woman sees a fertility specialist, Dr. Ole Christiansen said during a press briefing at the annual meeting of the European Society of Reproduction and Embryology. Success is not related to treatment, since none exists for unexplained miscarriage. Instead, said Dr. Christiansen of Rigshospitalet, Copenhagen, the declining incidence of birth over 5 years is probably related to increasing maternal age with each attempt, or to the decision to give up efforts to conceive.

Dr. Stef P. Kaandorp, whose study came to a similar conclusion, said the results of both are encouraging.

"Women with recurrent miscarriage can be reassured that their time to a subsequent conception is not significantly longer that that for fertile women without a history of miscarriage," said Dr. Kaandorp, a research fellow at the University of Amsterdam. "Recurrent miscarriage is extremely stressful for these women, and we hope that our study will give them hope and encourage them to keep trying for the baby they want so much."

Prof. Christiansen presented a population-based retrospective study conducted in Denmark. Data were extracted from the National Danish Birth registry and identified 987 women who had at least three consecutive miscarriages and had been referred to a specialist clinic between 1986 and 2008. All of these women were aged 20-46 years at the time of referral. About one-third had some prior fertility treatments, including hormones, anticoagulants, and intravenous immunoglobulin.

Overall, 66% of the women (651) achieved a live birth after the consultation, Dr. Christiansen said. The highest rate occurred within the first 15 months of the consultation (71%). "The curve declines very rapidly after the first year after the consultation, then after 5 years it really flattens out," he said. "Only 2%-3% are likely to have a child after that."

Subgroup analyses found that increasing maternal age and the number of prior miscarriages were significantly associated with a continued rate of unsuccessful pregnancy. Nor were prior infertility treatments related to a later live birth, he said.

However, the new data should allow researchers to create a risk estimate graph that can predict the chance of a live birth much more precisely. "Instead of giving these women an uncertain risk estimate [for future live birth], we can now combine their age and number of miscarriages to give them a closer estimate of a live birth, and that is what matters to these women," he said.

Future research on this same cohort may look at what factors the male partner brings to the picture of recurrent miscarriage – if any.

In the second study, Dr. Kaandorp conducted a subanalysis of the ALIFE trial – a randomized, placebo-controlled study that showed neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate among women with unexplained recurrent miscarriage; the study ran from 2004-2008 (N. Engl. J. Med. 2010;362:1586-96).

Of the 364 women enrolled in that trial, Dr. Kaandorp identified 251 who had at least two miscarriages with a gestational age of 20 weeks or less and examined their subsequent rates of conception and live birth.

Of the cohort, 213 became naturally pregnant during by 2009. The median time to conception, regardless of outcome, was 21 weeks, although the range was 8-55 weeks. The cumulative pregnancy rate was 56% after 6 months, 74% after 12 months, and 86% after 24 months.

Of those who did conceive, 139 gave birth to a living child; 69 experienced another miscarriage; 2 had an ectopic pregnancy; 2 terminated the pregnancy; and 1 had an intrauterine death.

The presence of the Factor V Leiden genetic condition was the only factor significantly related to a shorter time to pregnancy; it increased by 91% the chance of conception by 11 weeks, compared with noncarriers.

"We should be cautious with this finding, because it only occurred in 11 women," Dr. Kaandorp noted. "At this point, I think we can only see it as hypothesis generating."

Neither Dr. Christiansen nor Dr. Kaandorp had any financial disclosures.

Major Finding: One-third of children with cyclic vomiting syndrome showed metabolic testing results suggestive of mitochondrial or fatty acid oxidation dysfunction.

Data Source: A case series of 106 children with the disorder.

Disclosures: Dr. Rothner reported having no financial disclosures.

WASHINGTON – About a third of children with cyclic vomiting syndrome appear to have some metabolic condition, either mitochondrial dysfunction, fatty acid oxidation dysfunction, or a combination of both.

Unfortunately, there seems to be neither rhyme nor reason to the pattern. “Some showed the abnormalities only when well, some showed them only when acutely ill, and some showed them all the time,” Dr. David Rothner said at the meeting.

Dr. Rothner, director of the Pediatric/Adolescent Headache Program at the Cleveland Clinic, and his colleagues presented the largest-to-date case series of metabolic testing in children with cyclic vomiting syndrome. Considered one of the three subtypes of migraine, cyclic vomiting is a debilitating illness with no known etiology and virtually no physical abnormalities that account for its occurrence.

The condition is a chronic disorder characterized by repeated, stereotypical vomiting episodes accompanied by severe nausea and sometimes by headache. The four components to the syndrome include the prodrome, when severe nausea is present; the severe emetic phase; the postemetic phase; and the time between cycles, during which the patient is entirely well.

Most frequently, the vomiting episode begins between 4 and 6 a.m. “During a spell, a child can vomit every 10-15 minutes, for up to 2 days. There is more vomiting with this syndrome than in any other disease known to man.”

Diagnosis can be made only by ruling out every possible physical cause.

“Often, the time from the first episode until diagnosis can be 3 or 4 years, which is tragic,” he said.

The prospective cohort consisted of 106 consecutive patients seen at the clinic from 2007 to 2010. Most were 8 or 9 years old, male (57%), and white (77%), and “most importantly, 26% had a personal history of migraine, which did not occur during the vomiting.”

Most of the children (71%) also had a family history of migraine; 10% had a family history of epilepsy.

The episodes occurred an average every 4 weeks. The mean duration of the acute phase was 25 hours, with a mean of 18 vomits during that time, up to 5 per hour. “There was complete resolution of symptoms between the spells in 88% of these children,” Dr. Rothner said.

Most children (73%) had a prodromal phase, usually abdominal pain and nausea. There were some identifiable triggers for 66%, including viral illness, and motion sickness. Along with vomiting, 25% of the children had some autonomic symptom, including fever and hypertension.

Of the 42 patients who underwent magnetic resonance imaging, 57% had normal results. “Some of them already had the abnormalities recognized before the disorder began, but none of them had anything to do with the vomiting,” Dr. Rothner said.

He and his team also performed abdominal ultrasound on 41 children during the acute phase to rule out intestinal malrotation or volvulus. There were no gastrointestinal abnormalities related to vomiting. Esophagogastroduodenoscopies in 27 patients showed six cases of gastritis, but no serious issues.

The investigators aimed to perform metabolic testing of blood and urine during both the well and ill phase in all children. At least some testing was accomplished in 58. One-third of the children tested during the ill or well phase, or during both, showed some sign of mitochondrial dysfunction or abnormal oxidation of fatty acid.

But the results were very difficult to interpret, Dr. Rothner said. “Of the 16 patients who had testing at both phases, 13 had abnormalities. But three showed mitochondrial dysfunction when well and not when ill, four had abnormalities when ill but not when well, and another three had some combination of mitochondrial and fatty acid dysfunction during both times. When we looked at the metabolic testing based on timing, we expected to find more abnormalities at the time of acute illness, but this was not the case. The results were not consistent.”

There is no universally accepted treatment for the disorder. “Nothing controls it or makes it go away,” Dr. Rothner said. For prophylactic treatment, about half of the group experienced some benefit from amitriptyline. During the acute phase, 85 children tried high-dose oral ondansetron, which improved or resolved symptoms in 66%. Now, based on the metabolic testing, some of the children in the group also receive carnitine and coenzyme Q10, which Dr. Rothner said confers at least some benefit to about half the group.

The children are part of a continuous study which Dr. Rothner hopes will shed more light on the disorder's connection with metabolic dysfunction.

Major Finding: One-third of children with cyclic vomiting syndrome showed metabolic testing results suggestive of mitochondrial or fatty acid oxidation dysfunction.

Data Source: A case series of 106 children with the disorder.

Disclosures: Dr. Rothner reported having no financial disclosures.

WASHINGTON – About a third of children with cyclic vomiting syndrome appear to have some metabolic condition, either mitochondrial dysfunction, fatty acid oxidation dysfunction, or a combination of both.

Unfortunately, there seems to be neither rhyme nor reason to the pattern. “Some showed the abnormalities only when well, some showed them only when acutely ill, and some showed them all the time,” Dr. David Rothner said at the meeting.

Dr. Rothner, director of the Pediatric/Adolescent Headache Program at the Cleveland Clinic, and his colleagues presented the largest-to-date case series of metabolic testing in children with cyclic vomiting syndrome. Considered one of the three subtypes of migraine, cyclic vomiting is a debilitating illness with no known etiology and virtually no physical abnormalities that account for its occurrence.

The condition is a chronic disorder characterized by repeated, stereotypical vomiting episodes accompanied by severe nausea and sometimes by headache. The four components to the syndrome include the prodrome, when severe nausea is present; the severe emetic phase; the postemetic phase; and the time between cycles, during which the patient is entirely well.

Most frequently, the vomiting episode begins between 4 and 6 a.m. “During a spell, a child can vomit every 10-15 minutes, for up to 2 days. There is more vomiting with this syndrome than in any other disease known to man.”

Diagnosis can be made only by ruling out every possible physical cause.

“Often, the time from the first episode until diagnosis can be 3 or 4 years, which is tragic,” he said.

The prospective cohort consisted of 106 consecutive patients seen at the clinic from 2007 to 2010. Most were 8 or 9 years old, male (57%), and white (77%), and “most importantly, 26% had a personal history of migraine, which did not occur during the vomiting.”

Most of the children (71%) also had a family history of migraine; 10% had a family history of epilepsy.

The episodes occurred an average every 4 weeks. The mean duration of the acute phase was 25 hours, with a mean of 18 vomits during that time, up to 5 per hour. “There was complete resolution of symptoms between the spells in 88% of these children,” Dr. Rothner said.

Most children (73%) had a prodromal phase, usually abdominal pain and nausea. There were some identifiable triggers for 66%, including viral illness, and motion sickness. Along with vomiting, 25% of the children had some autonomic symptom, including fever and hypertension.

Of the 42 patients who underwent magnetic resonance imaging, 57% had normal results. “Some of them already had the abnormalities recognized before the disorder began, but none of them had anything to do with the vomiting,” Dr. Rothner said.

He and his team also performed abdominal ultrasound on 41 children during the acute phase to rule out intestinal malrotation or volvulus. There were no gastrointestinal abnormalities related to vomiting. Esophagogastroduodenoscopies in 27 patients showed six cases of gastritis, but no serious issues.

The investigators aimed to perform metabolic testing of blood and urine during both the well and ill phase in all children. At least some testing was accomplished in 58. One-third of the children tested during the ill or well phase, or during both, showed some sign of mitochondrial dysfunction or abnormal oxidation of fatty acid.

But the results were very difficult to interpret, Dr. Rothner said. “Of the 16 patients who had testing at both phases, 13 had abnormalities. But three showed mitochondrial dysfunction when well and not when ill, four had abnormalities when ill but not when well, and another three had some combination of mitochondrial and fatty acid dysfunction during both times. When we looked at the metabolic testing based on timing, we expected to find more abnormalities at the time of acute illness, but this was not the case. The results were not consistent.”

There is no universally accepted treatment for the disorder. “Nothing controls it or makes it go away,” Dr. Rothner said. For prophylactic treatment, about half of the group experienced some benefit from amitriptyline. During the acute phase, 85 children tried high-dose oral ondansetron, which improved or resolved symptoms in 66%. Now, based on the metabolic testing, some of the children in the group also receive carnitine and coenzyme Q10, which Dr. Rothner said confers at least some benefit to about half the group.

The children are part of a continuous study which Dr. Rothner hopes will shed more light on the disorder's connection with metabolic dysfunction.

Major Finding: One-third of children with cyclic vomiting syndrome showed metabolic testing results suggestive of mitochondrial or fatty acid oxidation dysfunction.

Data Source: A case series of 106 children with the disorder.

Disclosures: Dr. Rothner reported having no financial disclosures.

WASHINGTON – About a third of children with cyclic vomiting syndrome appear to have some metabolic condition, either mitochondrial dysfunction, fatty acid oxidation dysfunction, or a combination of both.

Unfortunately, there seems to be neither rhyme nor reason to the pattern. “Some showed the abnormalities only when well, some showed them only when acutely ill, and some showed them all the time,” Dr. David Rothner said at the meeting.

Dr. Rothner, director of the Pediatric/Adolescent Headache Program at the Cleveland Clinic, and his colleagues presented the largest-to-date case series of metabolic testing in children with cyclic vomiting syndrome. Considered one of the three subtypes of migraine, cyclic vomiting is a debilitating illness with no known etiology and virtually no physical abnormalities that account for its occurrence.

The condition is a chronic disorder characterized by repeated, stereotypical vomiting episodes accompanied by severe nausea and sometimes by headache. The four components to the syndrome include the prodrome, when severe nausea is present; the severe emetic phase; the postemetic phase; and the time between cycles, during which the patient is entirely well.

Most frequently, the vomiting episode begins between 4 and 6 a.m. “During a spell, a child can vomit every 10-15 minutes, for up to 2 days. There is more vomiting with this syndrome than in any other disease known to man.”

Diagnosis can be made only by ruling out every possible physical cause.

“Often, the time from the first episode until diagnosis can be 3 or 4 years, which is tragic,” he said.

The prospective cohort consisted of 106 consecutive patients seen at the clinic from 2007 to 2010. Most were 8 or 9 years old, male (57%), and white (77%), and “most importantly, 26% had a personal history of migraine, which did not occur during the vomiting.”

Most of the children (71%) also had a family history of migraine; 10% had a family history of epilepsy.

The episodes occurred an average every 4 weeks. The mean duration of the acute phase was 25 hours, with a mean of 18 vomits during that time, up to 5 per hour. “There was complete resolution of symptoms between the spells in 88% of these children,” Dr. Rothner said.

Most children (73%) had a prodromal phase, usually abdominal pain and nausea. There were some identifiable triggers for 66%, including viral illness, and motion sickness. Along with vomiting, 25% of the children had some autonomic symptom, including fever and hypertension.

Of the 42 patients who underwent magnetic resonance imaging, 57% had normal results. “Some of them already had the abnormalities recognized before the disorder began, but none of them had anything to do with the vomiting,” Dr. Rothner said.

He and his team also performed abdominal ultrasound on 41 children during the acute phase to rule out intestinal malrotation or volvulus. There were no gastrointestinal abnormalities related to vomiting. Esophagogastroduodenoscopies in 27 patients showed six cases of gastritis, but no serious issues.

The investigators aimed to perform metabolic testing of blood and urine during both the well and ill phase in all children. At least some testing was accomplished in 58. One-third of the children tested during the ill or well phase, or during both, showed some sign of mitochondrial dysfunction or abnormal oxidation of fatty acid.

But the results were very difficult to interpret, Dr. Rothner said. “Of the 16 patients who had testing at both phases, 13 had abnormalities. But three showed mitochondrial dysfunction when well and not when ill, four had abnormalities when ill but not when well, and another three had some combination of mitochondrial and fatty acid dysfunction during both times. When we looked at the metabolic testing based on timing, we expected to find more abnormalities at the time of acute illness, but this was not the case. The results were not consistent.”

There is no universally accepted treatment for the disorder. “Nothing controls it or makes it go away,” Dr. Rothner said. For prophylactic treatment, about half of the group experienced some benefit from amitriptyline. During the acute phase, 85 children tried high-dose oral ondansetron, which improved or resolved symptoms in 66%. Now, based on the metabolic testing, some of the children in the group also receive carnitine and coenzyme Q10, which Dr. Rothner said confers at least some benefit to about half the group.

The children are part of a continuous study which Dr. Rothner hopes will shed more light on the disorder's connection with metabolic dysfunction.

Major Finding: Among 28 women with up to 10 migraines per month, there was no significant relationship between cognitive function and headache frequency.

Data Source: A subanalysis of the ongoing CAMP study.

Disclosures: The research was supported by grants from Coherex Medical, the John L. Locke Jr. Charitable Trust, NMT Medical, and the National Headache Foundation. Neither Dr. Jesurum not her coinvestigators had any relevant financial disclosures.

WASHINGTON – Women with a high burden of episodic migraine don't appear to have any related cognitive impairment.

A small prospective study has found that women with as many as 10 migraines per month scored well within the normal range on tests of learning and memory, efficiency and attention, and processing speed, Jill Jesurum, Ph.D., reported in a poster at the meeting.

“This is very good news for women with migraine,” said Dr. Jesurum, scientific director of the Swedish Heart and Vascular Institute at the Swedish Medical Center, Seattle. “I see migraine patients in my own clinic, and many are very worried because they feel they have some type of cognitive problems from their migraines.”

She presented a subanalysis of the CAMP (Comorbidities Associated With Migraine and Patent Foramen Ovale) study. The ongoing study aims to assess cognitive impairment and other comorbidities in at least 40 patients with migraine aura and a large patent foramen ovale, compared with migraineurs who do not have the heart defect.

Dr. Jesurum's substudy comprised 28 women with a high migraine burden. The subjects' mean age was 35 years. They had experienced migraines for a mean 19 years, with a mean of eight migraines each month. The MIDAS (Migraine Disability Assessment Test) and HIT-6 (Headache Impact Test–6) both showed that these women experienced severe disability with their migraines, with a mean MIDAS score of 40 and a mean HIT-6 score of 64. Depression and anxiety were minimal and moderate, according to mean test scores.

The women underwent a battery of cognitive testing during a headache-free period; they had no headache symptoms and no alcohol or opioid use during the 24 hours before the testing. The analysis controlled for antiepileptic agents as well as the use of NSAIDs and anticoagulant or antiplatelet drugs. A neuropsychologist who was blinded to the headache ratings administered and scored the tests.

“What we found was very encouraging,” Dr. Jesurum said in an interview. “These women with a very high migraine burden were functioning at a high cognitive level during their headache-free periods. All of them scored within one standard deviation in all of the tests.”

A subanalysis of the data showed no significant relationships between cognitive function scores and monthly migraine frequency. However, Dr. Jesurum noted, “When we looked at migraine burden and disability as measured by the HIT-6 and the MIDAS, we did see many significant inverse relationships between migraine burden, disability, and cognitive function. The higher the migraine burden and the higher the disability, the lower the cognitive functions were, but that relationship was not significant when [we looked] at monthly migraine frequency.”

This may reflect the perceived intensity of migraines, she said. “One woman might have two migraines a month, but if they totally wreck her life and she can't work or take care of her children, that may negatively impact her cognitive function. On the other hand, another may have 5 or even 10 migraines a month, but if she's able to treat them adequately and go about her daily life, they may not affect her cognitive function.”

Because the study was so small did not have a comparator, it must be regarded as exploratory, Dr. Jesurum noted.

All of the women with a high burden of episodic migraine scored within one standard deviation on cognitive tests.

Source DR. JESURUM

Major Finding: Among 28 women with up to 10 migraines per month, there was no significant relationship between cognitive function and headache frequency.

Data Source: A subanalysis of the ongoing CAMP study.

Disclosures: The research was supported by grants from Coherex Medical, the John L. Locke Jr. Charitable Trust, NMT Medical, and the National Headache Foundation. Neither Dr. Jesurum not her coinvestigators had any relevant financial disclosures.

WASHINGTON – Women with a high burden of episodic migraine don't appear to have any related cognitive impairment.

A small prospective study has found that women with as many as 10 migraines per month scored well within the normal range on tests of learning and memory, efficiency and attention, and processing speed, Jill Jesurum, Ph.D., reported in a poster at the meeting.

“This is very good news for women with migraine,” said Dr. Jesurum, scientific director of the Swedish Heart and Vascular Institute at the Swedish Medical Center, Seattle. “I see migraine patients in my own clinic, and many are very worried because they feel they have some type of cognitive problems from their migraines.”

She presented a subanalysis of the CAMP (Comorbidities Associated With Migraine and Patent Foramen Ovale) study. The ongoing study aims to assess cognitive impairment and other comorbidities in at least 40 patients with migraine aura and a large patent foramen ovale, compared with migraineurs who do not have the heart defect.

Dr. Jesurum's substudy comprised 28 women with a high migraine burden. The subjects' mean age was 35 years. They had experienced migraines for a mean 19 years, with a mean of eight migraines each month. The MIDAS (Migraine Disability Assessment Test) and HIT-6 (Headache Impact Test–6) both showed that these women experienced severe disability with their migraines, with a mean MIDAS score of 40 and a mean HIT-6 score of 64. Depression and anxiety were minimal and moderate, according to mean test scores.

The women underwent a battery of cognitive testing during a headache-free period; they had no headache symptoms and no alcohol or opioid use during the 24 hours before the testing. The analysis controlled for antiepileptic agents as well as the use of NSAIDs and anticoagulant or antiplatelet drugs. A neuropsychologist who was blinded to the headache ratings administered and scored the tests.

“What we found was very encouraging,” Dr. Jesurum said in an interview. “These women with a very high migraine burden were functioning at a high cognitive level during their headache-free periods. All of them scored within one standard deviation in all of the tests.”

A subanalysis of the data showed no significant relationships between cognitive function scores and monthly migraine frequency. However, Dr. Jesurum noted, “When we looked at migraine burden and disability as measured by the HIT-6 and the MIDAS, we did see many significant inverse relationships between migraine burden, disability, and cognitive function. The higher the migraine burden and the higher the disability, the lower the cognitive functions were, but that relationship was not significant when [we looked] at monthly migraine frequency.”

This may reflect the perceived intensity of migraines, she said. “One woman might have two migraines a month, but if they totally wreck her life and she can't work or take care of her children, that may negatively impact her cognitive function. On the other hand, another may have 5 or even 10 migraines a month, but if she's able to treat them adequately and go about her daily life, they may not affect her cognitive function.”

Because the study was so small did not have a comparator, it must be regarded as exploratory, Dr. Jesurum noted.

All of the women with a high burden of episodic migraine scored within one standard deviation on cognitive tests.

Source DR. JESURUM

Major Finding: Among 28 women with up to 10 migraines per month, there was no significant relationship between cognitive function and headache frequency.

Data Source: A subanalysis of the ongoing CAMP study.

Disclosures: The research was supported by grants from Coherex Medical, the John L. Locke Jr. Charitable Trust, NMT Medical, and the National Headache Foundation. Neither Dr. Jesurum not her coinvestigators had any relevant financial disclosures.

WASHINGTON – Women with a high burden of episodic migraine don't appear to have any related cognitive impairment.

A small prospective study has found that women with as many as 10 migraines per month scored well within the normal range on tests of learning and memory, efficiency and attention, and processing speed, Jill Jesurum, Ph.D., reported in a poster at the meeting.

“This is very good news for women with migraine,” said Dr. Jesurum, scientific director of the Swedish Heart and Vascular Institute at the Swedish Medical Center, Seattle. “I see migraine patients in my own clinic, and many are very worried because they feel they have some type of cognitive problems from their migraines.”

She presented a subanalysis of the CAMP (Comorbidities Associated With Migraine and Patent Foramen Ovale) study. The ongoing study aims to assess cognitive impairment and other comorbidities in at least 40 patients with migraine aura and a large patent foramen ovale, compared with migraineurs who do not have the heart defect.

Dr. Jesurum's substudy comprised 28 women with a high migraine burden. The subjects' mean age was 35 years. They had experienced migraines for a mean 19 years, with a mean of eight migraines each month. The MIDAS (Migraine Disability Assessment Test) and HIT-6 (Headache Impact Test–6) both showed that these women experienced severe disability with their migraines, with a mean MIDAS score of 40 and a mean HIT-6 score of 64. Depression and anxiety were minimal and moderate, according to mean test scores.

The women underwent a battery of cognitive testing during a headache-free period; they had no headache symptoms and no alcohol or opioid use during the 24 hours before the testing. The analysis controlled for antiepileptic agents as well as the use of NSAIDs and anticoagulant or antiplatelet drugs. A neuropsychologist who was blinded to the headache ratings administered and scored the tests.

“What we found was very encouraging,” Dr. Jesurum said in an interview. “These women with a very high migraine burden were functioning at a high cognitive level during their headache-free periods. All of them scored within one standard deviation in all of the tests.”

A subanalysis of the data showed no significant relationships between cognitive function scores and monthly migraine frequency. However, Dr. Jesurum noted, “When we looked at migraine burden and disability as measured by the HIT-6 and the MIDAS, we did see many significant inverse relationships between migraine burden, disability, and cognitive function. The higher the migraine burden and the higher the disability, the lower the cognitive functions were, but that relationship was not significant when [we looked] at monthly migraine frequency.”

This may reflect the perceived intensity of migraines, she said. “One woman might have two migraines a month, but if they totally wreck her life and she can't work or take care of her children, that may negatively impact her cognitive function. On the other hand, another may have 5 or even 10 migraines a month, but if she's able to treat them adequately and go about her daily life, they may not affect her cognitive function.”

Because the study was so small did not have a comparator, it must be regarded as exploratory, Dr. Jesurum noted.

All of the women with a high burden of episodic migraine scored within one standard deviation on cognitive tests.

Source DR. JESURUM

Major Finding: In a sample of 5,600 people with episodic migraine, 41% reported at least one unmet medical need.

Data Source: An analysis of more than 20,000 people from the American Migraine Prevalence and Prevention Study.

Disclosures: The American Migraine Prevalence and Prevention Study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck. Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said. “You all know this is nothing new. You keep working to meet your patients' needs while considering side effects, cost, effectiveness, and speed of onset.” But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

▸ Dissatisfaction with current acute treatment (assessed by the three-item summary from the Patient Perception of Migraine Questionnaire).

▸ Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

▸ Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

▸ Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

▸ History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs.

Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

“When we looked at the three most frequently reported areas, we saw an interesting overlap,” Dr. Buse said. “Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas.”

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

To see a video interview with Dr. Buse, scan the QR code or visit www.clinicalneurologynews.com

Major Finding: In a sample of 5,600 people with episodic migraine, 41% reported at least one unmet medical need.

Data Source: An analysis of more than 20,000 people from the American Migraine Prevalence and Prevention Study.

Disclosures: The American Migraine Prevalence and Prevention Study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck. Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said. “You all know this is nothing new. You keep working to meet your patients' needs while considering side effects, cost, effectiveness, and speed of onset.” But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

▸ Dissatisfaction with current acute treatment (assessed by the three-item summary from the Patient Perception of Migraine Questionnaire).

▸ Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

▸ Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

▸ Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

▸ History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs.

Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

“When we looked at the three most frequently reported areas, we saw an interesting overlap,” Dr. Buse said. “Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas.”

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

To see a video interview with Dr. Buse, scan the QR code or visit www.clinicalneurologynews.com

Major Finding: In a sample of 5,600 people with episodic migraine, 41% reported at least one unmet medical need.

Data Source: An analysis of more than 20,000 people from the American Migraine Prevalence and Prevention Study.

Disclosures: The American Migraine Prevalence and Prevention Study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck. Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said. “You all know this is nothing new. You keep working to meet your patients' needs while considering side effects, cost, effectiveness, and speed of onset.” But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

▸ Dissatisfaction with current acute treatment (assessed by the three-item summary from the Patient Perception of Migraine Questionnaire).

▸ Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

▸ Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

▸ Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

▸ History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs.

Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

“When we looked at the three most frequently reported areas, we saw an interesting overlap,” Dr. Buse said. “Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas.”

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

To see a video interview with Dr. Buse, scan the QR code or visit www.clinicalneurologynews.com

SAN DIEGO – An intestinal biopsy is almost always necessary to confirm celiac disease and is a must before committing a patient to the only effective treatment – a lifelong gluten-free diet.

Rheumatologists are starting to recognize that celiac disease occurs at higher rates in patients with such autoimmune diseases as myositis than in the general population (

Sticking to such a restricted diet is difficult and expensive, Dr. Sheila Crowe said at the meeting. “A lifelong gluten-free diet sounds simple, unless you're the patient. … Eating out is very difficult, especially for children and teens who face a lot of peer pressure. And eating gluten free at home is expensive. Studies in the United States, Canada, and the United Kingdom confirm that a lifelong diet of gluten-free foods costs about three times more than a normal diet,” said Dr. Crowe, professor in the division of gastroenterology and hepatology at the University of Virginia, Charlottesville.

Because treating celiac disease requires this lifelong commitment, a positive serologic test is not enough to rule it in, she said. Nor are any of the available immunologic tests, including the most widely used, tissue transglutaminase IgA (tTG IgA), specific enough to replace intestinal biopsy as the sole method for reliably diagnosing celiac disease. “A positive tTG test is not enough to place a person on this lifelong treatment without confirmation from an intestinal biopsy,” she said. “This is especially important for children, because of the higher likelihood of false positives in that group.”

tTG IgA has a very high sensitivity and specificity, but it is not perfect, Dr. Crowe said. “If you have a patient with clinical symptoms and the tTG comes back negative, there is still a 10% chance that's a false negative. Another scenario could be a patient who has an autoimmune disease or a relative with celiac, and is experiencing celiac symptoms. If the tTG came back negative on that person, I would still do an endoscopy.”

The only possible exception might be a patient with celiac symptoms who already has biopsy-proven dermatitis herpetiformis, with the classic immunofluorescent deposits at the dermal-epidermal junction. “If you biopsy these patients, the intestine will show the changes associated with celiac disease every time,” Dr. Crowe said.

Celiac disease is no longer considered a disorder of childhood. “The disease is there lifelong. It appears you cannot suppress the immune response,” she said.

The intestine rapidly responds to a gluten-free diet, “But the tendency to have an immunologic response to gluten is always there,” Dr. Crowe said.

Relapses are common. Patients are most likely to “fall off” the diet when symptoms begin to abate, she said. They may simply feel “cured” and resume old eating patterns, or they may drop the diet because of changes that can occur as the intestine heals. If patients “had diarrhea and malabsorption of nutrients, they might find themselves getting constipated and gaining weight on the gluten-free diet, fall off, and get ill again. Even if the intestine is healed, the vast majority of data tell us that patients will relapse,” at some point after abandoning the dietary restriction, Dr. Crowe said.

This can lead to the development of refractory celiac disease, in which the intestine fails to recover despite a gluten-free diet. These patients may be unable to fully absorb nutrients and need supplemental feeding methods.

The goal of celiac management is to promote intestinal healing, optimize nutrition, and avoid long-term damage, Dr. Crowe said. “It's key to bring in a knowledgeable dietitian to help. And I mean knowledgeable – not someone who is going to hand your patient a diet sheet and that's all.”

Many celiac patients are already nutritionally compromised at the time of diagnosis. “This is the time to measure their nutritional parameters,” Dr. Crowe said. “They may need supplements. Many are deficient in vitamin D, iron, folate, zinc, or other trace elements.”

The risks of untreated disease “are not inconsequential.” Patients can develop problems related to nutrient malabsorption, including osteopenia, infertility, miscarriage, and intrauterine growth restriction, and are four times more likely than is the general population to develop a malignancy.

Dr. Crowe gets royalties from a book on celiac disease.

SAN DIEGO – An intestinal biopsy is almost always necessary to confirm celiac disease and is a must before committing a patient to the only effective treatment – a lifelong gluten-free diet.

Rheumatologists are starting to recognize that celiac disease occurs at higher rates in patients with such autoimmune diseases as myositis than in the general population (

Sticking to such a restricted diet is difficult and expensive, Dr. Sheila Crowe said at the meeting. “A lifelong gluten-free diet sounds simple, unless you're the patient. … Eating out is very difficult, especially for children and teens who face a lot of peer pressure. And eating gluten free at home is expensive. Studies in the United States, Canada, and the United Kingdom confirm that a lifelong diet of gluten-free foods costs about three times more than a normal diet,” said Dr. Crowe, professor in the division of gastroenterology and hepatology at the University of Virginia, Charlottesville.

Because treating celiac disease requires this lifelong commitment, a positive serologic test is not enough to rule it in, she said. Nor are any of the available immunologic tests, including the most widely used, tissue transglutaminase IgA (tTG IgA), specific enough to replace intestinal biopsy as the sole method for reliably diagnosing celiac disease. “A positive tTG test is not enough to place a person on this lifelong treatment without confirmation from an intestinal biopsy,” she said. “This is especially important for children, because of the higher likelihood of false positives in that group.”

tTG IgA has a very high sensitivity and specificity, but it is not perfect, Dr. Crowe said. “If you have a patient with clinical symptoms and the tTG comes back negative, there is still a 10% chance that's a false negative. Another scenario could be a patient who has an autoimmune disease or a relative with celiac, and is experiencing celiac symptoms. If the tTG came back negative on that person, I would still do an endoscopy.”

The only possible exception might be a patient with celiac symptoms who already has biopsy-proven dermatitis herpetiformis, with the classic immunofluorescent deposits at the dermal-epidermal junction. “If you biopsy these patients, the intestine will show the changes associated with celiac disease every time,” Dr. Crowe said.

Celiac disease is no longer considered a disorder of childhood. “The disease is there lifelong. It appears you cannot suppress the immune response,” she said.

The intestine rapidly responds to a gluten-free diet, “But the tendency to have an immunologic response to gluten is always there,” Dr. Crowe said.

Relapses are common. Patients are most likely to “fall off” the diet when symptoms begin to abate, she said. They may simply feel “cured” and resume old eating patterns, or they may drop the diet because of changes that can occur as the intestine heals. If patients “had diarrhea and malabsorption of nutrients, they might find themselves getting constipated and gaining weight on the gluten-free diet, fall off, and get ill again. Even if the intestine is healed, the vast majority of data tell us that patients will relapse,” at some point after abandoning the dietary restriction, Dr. Crowe said.

This can lead to the development of refractory celiac disease, in which the intestine fails to recover despite a gluten-free diet. These patients may be unable to fully absorb nutrients and need supplemental feeding methods.

The goal of celiac management is to promote intestinal healing, optimize nutrition, and avoid long-term damage, Dr. Crowe said. “It's key to bring in a knowledgeable dietitian to help. And I mean knowledgeable – not someone who is going to hand your patient a diet sheet and that's all.”

Many celiac patients are already nutritionally compromised at the time of diagnosis. “This is the time to measure their nutritional parameters,” Dr. Crowe said. “They may need supplements. Many are deficient in vitamin D, iron, folate, zinc, or other trace elements.”

The risks of untreated disease “are not inconsequential.” Patients can develop problems related to nutrient malabsorption, including osteopenia, infertility, miscarriage, and intrauterine growth restriction, and are four times more likely than is the general population to develop a malignancy.

Dr. Crowe gets royalties from a book on celiac disease.

SAN DIEGO – An intestinal biopsy is almost always necessary to confirm celiac disease and is a must before committing a patient to the only effective treatment – a lifelong gluten-free diet.

Rheumatologists are starting to recognize that celiac disease occurs at higher rates in patients with such autoimmune diseases as myositis than in the general population (

Sticking to such a restricted diet is difficult and expensive, Dr. Sheila Crowe said at the meeting. “A lifelong gluten-free diet sounds simple, unless you're the patient. … Eating out is very difficult, especially for children and teens who face a lot of peer pressure. And eating gluten free at home is expensive. Studies in the United States, Canada, and the United Kingdom confirm that a lifelong diet of gluten-free foods costs about three times more than a normal diet,” said Dr. Crowe, professor in the division of gastroenterology and hepatology at the University of Virginia, Charlottesville.

Because treating celiac disease requires this lifelong commitment, a positive serologic test is not enough to rule it in, she said. Nor are any of the available immunologic tests, including the most widely used, tissue transglutaminase IgA (tTG IgA), specific enough to replace intestinal biopsy as the sole method for reliably diagnosing celiac disease. “A positive tTG test is not enough to place a person on this lifelong treatment without confirmation from an intestinal biopsy,” she said. “This is especially important for children, because of the higher likelihood of false positives in that group.”

tTG IgA has a very high sensitivity and specificity, but it is not perfect, Dr. Crowe said. “If you have a patient with clinical symptoms and the tTG comes back negative, there is still a 10% chance that's a false negative. Another scenario could be a patient who has an autoimmune disease or a relative with celiac, and is experiencing celiac symptoms. If the tTG came back negative on that person, I would still do an endoscopy.”

The only possible exception might be a patient with celiac symptoms who already has biopsy-proven dermatitis herpetiformis, with the classic immunofluorescent deposits at the dermal-epidermal junction. “If you biopsy these patients, the intestine will show the changes associated with celiac disease every time,” Dr. Crowe said.

Celiac disease is no longer considered a disorder of childhood. “The disease is there lifelong. It appears you cannot suppress the immune response,” she said.

The intestine rapidly responds to a gluten-free diet, “But the tendency to have an immunologic response to gluten is always there,” Dr. Crowe said.

Relapses are common. Patients are most likely to “fall off” the diet when symptoms begin to abate, she said. They may simply feel “cured” and resume old eating patterns, or they may drop the diet because of changes that can occur as the intestine heals. If patients “had diarrhea and malabsorption of nutrients, they might find themselves getting constipated and gaining weight on the gluten-free diet, fall off, and get ill again. Even if the intestine is healed, the vast majority of data tell us that patients will relapse,” at some point after abandoning the dietary restriction, Dr. Crowe said.

This can lead to the development of refractory celiac disease, in which the intestine fails to recover despite a gluten-free diet. These patients may be unable to fully absorb nutrients and need supplemental feeding methods.

The goal of celiac management is to promote intestinal healing, optimize nutrition, and avoid long-term damage, Dr. Crowe said. “It's key to bring in a knowledgeable dietitian to help. And I mean knowledgeable – not someone who is going to hand your patient a diet sheet and that's all.”

Many celiac patients are already nutritionally compromised at the time of diagnosis. “This is the time to measure their nutritional parameters,” Dr. Crowe said. “They may need supplements. Many are deficient in vitamin D, iron, folate, zinc, or other trace elements.”

The risks of untreated disease “are not inconsequential.” Patients can develop problems related to nutrient malabsorption, including osteopenia, infertility, miscarriage, and intrauterine growth restriction, and are four times more likely than is the general population to develop a malignancy.

Dr. Crowe gets royalties from a book on celiac disease.

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton.

Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting.

“I still recommend allopurinol as the initial treatment, because you don't need a 24-hour urine collection to give it; it's effective in both overproducers and underexcretors [of uric acid]; it can be taken just once a day; and it's safe and effective for those with mild renal insufficiency when the dose is adjusted,” said Dr. Pendleton, an internist in Roanoke, Va.

“Generic allopurinol costs about $15 per month. The brand name costs about $43 per month. But the price for febuxostat comes in at about $156 per month,” he said.

With either drug, the goal is to lower uric acid levels to below 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks (Arthritis Rheum. 2004; 51:321-5).

In the study, “among the 81 patients with a uric acid of less than 6 mg/dL, 88% had no recurrent attacks during the 3-year observational period,” he said.

Allopurinol has been the “standby drug” for gouty arthritis for 60 years, and still performs admirably, he noted. Most initial doses range from 50 to 300 mg/day, but “some recent studies suggest that only 25% of patients will reach the uric acid target on that regimen. For many patients, we need to increase the dose to get that level down.”

The dose should be incrementally increased every 3–4 weeks to reach the uric acid target level; doses of up to 800 mg/day are approved for this indication. “But if you're not able to achieve this desired level by pushing the dose close to 800 mg, I would consider trying febuxostat.”

Febuxostat, a xanthine oxidase inhibitor, is more selective and potent than allopurnol. “It's metabolized in the liver and very little of the active drug is excreted renally, raising the possibility that it might be safer in patients with mild to moderate renal insufficiency,” Dr. Pendleton said.

It's not easy to fully compare the two, because all three of the studies on the basis of which febuxostat was approved used a fixed-dose allopurinol regimen. “None of them allowed the total upward titration of allopurinol for a fair comparison,” Dr. Pendleton pointed out.

The studies concluded that 40 mg of febuxostat was as effective as 300 mg of allopurinol. “The higher dose [of febuxostat 80 mg] seemed to be more effective than 400 mg allopurinol, but again, the studies did not allow for an upward titration” of the comparator, he said.

Although none of the patients in those trials had a creatinine level of more than 2.5 mg/dL, “a short-term study suggests that febuxostat dosing would not need to be adjusted even with a very low creatinine clearance [of 10–29 mL/min]. But just the same I would be very careful in that setting,” Dr. Pendleton said (Am. J. Ther. 2005;12:22-34).

Dr. Pendleton said he had no disclosures.

Allopurinol effectively prevents gout crystals (above) and is a cost-effective therapy.

Source ©Elsevier Inc.

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton.

Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting.

“I still recommend allopurinol as the initial treatment, because you don't need a 24-hour urine collection to give it; it's effective in both overproducers and underexcretors [of uric acid]; it can be taken just once a day; and it's safe and effective for those with mild renal insufficiency when the dose is adjusted,” said Dr. Pendleton, an internist in Roanoke, Va.

“Generic allopurinol costs about $15 per month. The brand name costs about $43 per month. But the price for febuxostat comes in at about $156 per month,” he said.

With either drug, the goal is to lower uric acid levels to below 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks (Arthritis Rheum. 2004; 51:321-5).

In the study, “among the 81 patients with a uric acid of less than 6 mg/dL, 88% had no recurrent attacks during the 3-year observational period,” he said.

Allopurinol has been the “standby drug” for gouty arthritis for 60 years, and still performs admirably, he noted. Most initial doses range from 50 to 300 mg/day, but “some recent studies suggest that only 25% of patients will reach the uric acid target on that regimen. For many patients, we need to increase the dose to get that level down.”

The dose should be incrementally increased every 3–4 weeks to reach the uric acid target level; doses of up to 800 mg/day are approved for this indication. “But if you're not able to achieve this desired level by pushing the dose close to 800 mg, I would consider trying febuxostat.”

Febuxostat, a xanthine oxidase inhibitor, is more selective and potent than allopurnol. “It's metabolized in the liver and very little of the active drug is excreted renally, raising the possibility that it might be safer in patients with mild to moderate renal insufficiency,” Dr. Pendleton said.

It's not easy to fully compare the two, because all three of the studies on the basis of which febuxostat was approved used a fixed-dose allopurinol regimen. “None of them allowed the total upward titration of allopurinol for a fair comparison,” Dr. Pendleton pointed out.

The studies concluded that 40 mg of febuxostat was as effective as 300 mg of allopurinol. “The higher dose [of febuxostat 80 mg] seemed to be more effective than 400 mg allopurinol, but again, the studies did not allow for an upward titration” of the comparator, he said.

Although none of the patients in those trials had a creatinine level of more than 2.5 mg/dL, “a short-term study suggests that febuxostat dosing would not need to be adjusted even with a very low creatinine clearance [of 10–29 mL/min]. But just the same I would be very careful in that setting,” Dr. Pendleton said (Am. J. Ther. 2005;12:22-34).

Dr. Pendleton said he had no disclosures.

Allopurinol effectively prevents gout crystals (above) and is a cost-effective therapy.

Source ©Elsevier Inc.

SAN DIEGO – Allopurinol should remain the first-line agent for gout prophylaxis, despite competition from a newer drug, febuxostat, according to Dr. John Pendleton.

Allopurinol is very effective, can be safely titrated for those with renal impairment, and is the most cost-effective option, he said at the meeting.

“I still recommend allopurinol as the initial treatment, because you don't need a 24-hour urine collection to give it; it's effective in both overproducers and underexcretors [of uric acid]; it can be taken just once a day; and it's safe and effective for those with mild renal insufficiency when the dose is adjusted,” said Dr. Pendleton, an internist in Roanoke, Va.

“Generic allopurinol costs about $15 per month. The brand name costs about $43 per month. But the price for febuxostat comes in at about $156 per month,” he said.

With either drug, the goal is to lower uric acid levels to below 6 mg/dL, said Dr. Pendleton, referring to a retrospective study of 276 patients with recurrent gout attacks (Arthritis Rheum. 2004; 51:321-5).

In the study, “among the 81 patients with a uric acid of less than 6 mg/dL, 88% had no recurrent attacks during the 3-year observational period,” he said.

Allopurinol has been the “standby drug” for gouty arthritis for 60 years, and still performs admirably, he noted. Most initial doses range from 50 to 300 mg/day, but “some recent studies suggest that only 25% of patients will reach the uric acid target on that regimen. For many patients, we need to increase the dose to get that level down.”

The dose should be incrementally increased every 3–4 weeks to reach the uric acid target level; doses of up to 800 mg/day are approved for this indication. “But if you're not able to achieve this desired level by pushing the dose close to 800 mg, I would consider trying febuxostat.”

Febuxostat, a xanthine oxidase inhibitor, is more selective and potent than allopurnol. “It's metabolized in the liver and very little of the active drug is excreted renally, raising the possibility that it might be safer in patients with mild to moderate renal insufficiency,” Dr. Pendleton said.

It's not easy to fully compare the two, because all three of the studies on the basis of which febuxostat was approved used a fixed-dose allopurinol regimen. “None of them allowed the total upward titration of allopurinol for a fair comparison,” Dr. Pendleton pointed out.

The studies concluded that 40 mg of febuxostat was as effective as 300 mg of allopurinol. “The higher dose [of febuxostat 80 mg] seemed to be more effective than 400 mg allopurinol, but again, the studies did not allow for an upward titration” of the comparator, he said.

Although none of the patients in those trials had a creatinine level of more than 2.5 mg/dL, “a short-term study suggests that febuxostat dosing would not need to be adjusted even with a very low creatinine clearance [of 10–29 mL/min]. But just the same I would be very careful in that setting,” Dr. Pendleton said (Am. J. Ther. 2005;12:22-34).

Dr. Pendleton said he had no disclosures.

Allopurinol effectively prevents gout crystals (above) and is a cost-effective therapy.

Source ©Elsevier Inc.

The Food and Drug Administration has unveiled the final nine warning images that will appear on cigarette packages by 2012 – graphic photos and drawings intended to educate and even deter consumers from buying cigarettes.

The images are required by the 2009 Tobacco Control Act, according to FDA spokesman Jeffrey Ventura, who added that these are the first changes to cigarette pack warnings in 25 years. By Oct. 22, 2012, cigarette manufacturers will no longer be able to distribute cigarettes for sale in the United States unless they display these warnings.

The law required the warnings to cover the top half of the front and back of cigarette packs and 20% of cigarette advertisements, and they must contain color graphics depicting the negative health consequences of smoking.

“This is something Congress wanted to happen and mandated that the FDA carry out,” Mr. Ventura said in an interview. Based on a study of 18,000 smokers conducted for the FDA by RTI International, federal officials said they firmly believe that visually communicating smoking's harm will deter cigarette consumption over the long run.

The images include tobacco-diseased lungs beside healthy lungs, a corpse in casket, a man exhaling smoke though a tracheostomy, and lip cancer. There are also several cartoons and photos of mothers blowing smoke into infants' faces. One positive image shows a burly man exposing a T-shirt saying, “I Quit.”

Blunt statements accompany each image, intended to drive home the messages that cigarette smoke not only directly harms the smoker, but the smokers' children and people in close proximity.

“The introduction of these warnings is expected to have a significant public health impact by decreasing the number of smokers, resulting in lives saved, increased life expectancy, and improved health status,” FDA officials said in a statement.

“Eliciting strong emotional and cognitive reactions to the graphic cigarette warning label enhances recall and processing of the health warning, which helps ensure that the warning is better processed, understood, and remembered,” the study said. “As attitudes and beliefs change, they eventually lead to changes in intentions to quit or start smoking and then later to lower smoking initiation and successful cessation. The time scale on which this behavior change process occurs is largely unknown in the context of the impact of exposure to graphic warning labels on smoking behaviors, but the effects on behavior change are unlikely to be immediate or short-term.”

Nevertheless, groups promoting antitobacco messages – including the American Heart Association – strongly believe that the warnings will enhance consumer education and change behavior.

“Undoubtedly, the new graphic health warnings will heighten awareness about the dangers of smoking and, more importantly, encourage smokers to quit and discourage smoking initiation,” an AHA press statement read. “We're confident that the new labels will move us closer to our goal of making the nation 100% smoke free.”

Any one of nine images must appear on cigarette packs by Oct. 22, 2012.

Source Courtesy U.S. Food and Drug Administration

The Food and Drug Administration has unveiled the final nine warning images that will appear on cigarette packages by 2012 – graphic photos and drawings intended to educate and even deter consumers from buying cigarettes.

The images are required by the 2009 Tobacco Control Act, according to FDA spokesman Jeffrey Ventura, who added that these are the first changes to cigarette pack warnings in 25 years. By Oct. 22, 2012, cigarette manufacturers will no longer be able to distribute cigarettes for sale in the United States unless they display these warnings.

The law required the warnings to cover the top half of the front and back of cigarette packs and 20% of cigarette advertisements, and they must contain color graphics depicting the negative health consequences of smoking.

“This is something Congress wanted to happen and mandated that the FDA carry out,” Mr. Ventura said in an interview. Based on a study of 18,000 smokers conducted for the FDA by RTI International, federal officials said they firmly believe that visually communicating smoking's harm will deter cigarette consumption over the long run.

The images include tobacco-diseased lungs beside healthy lungs, a corpse in casket, a man exhaling smoke though a tracheostomy, and lip cancer. There are also several cartoons and photos of mothers blowing smoke into infants' faces. One positive image shows a burly man exposing a T-shirt saying, “I Quit.”

Blunt statements accompany each image, intended to drive home the messages that cigarette smoke not only directly harms the smoker, but the smokers' children and people in close proximity.

“The introduction of these warnings is expected to have a significant public health impact by decreasing the number of smokers, resulting in lives saved, increased life expectancy, and improved health status,” FDA officials said in a statement.

“Eliciting strong emotional and cognitive reactions to the graphic cigarette warning label enhances recall and processing of the health warning, which helps ensure that the warning is better processed, understood, and remembered,” the study said. “As attitudes and beliefs change, they eventually lead to changes in intentions to quit or start smoking and then later to lower smoking initiation and successful cessation. The time scale on which this behavior change process occurs is largely unknown in the context of the impact of exposure to graphic warning labels on smoking behaviors, but the effects on behavior change are unlikely to be immediate or short-term.”

Nevertheless, groups promoting antitobacco messages – including the American Heart Association – strongly believe that the warnings will enhance consumer education and change behavior.

“Undoubtedly, the new graphic health warnings will heighten awareness about the dangers of smoking and, more importantly, encourage smokers to quit and discourage smoking initiation,” an AHA press statement read. “We're confident that the new labels will move us closer to our goal of making the nation 100% smoke free.”

Any one of nine images must appear on cigarette packs by Oct. 22, 2012.

Source Courtesy U.S. Food and Drug Administration

The Food and Drug Administration has unveiled the final nine warning images that will appear on cigarette packages by 2012 – graphic photos and drawings intended to educate and even deter consumers from buying cigarettes.

The images are required by the 2009 Tobacco Control Act, according to FDA spokesman Jeffrey Ventura, who added that these are the first changes to cigarette pack warnings in 25 years. By Oct. 22, 2012, cigarette manufacturers will no longer be able to distribute cigarettes for sale in the United States unless they display these warnings.

The law required the warnings to cover the top half of the front and back of cigarette packs and 20% of cigarette advertisements, and they must contain color graphics depicting the negative health consequences of smoking.

“This is something Congress wanted to happen and mandated that the FDA carry out,” Mr. Ventura said in an interview. Based on a study of 18,000 smokers conducted for the FDA by RTI International, federal officials said they firmly believe that visually communicating smoking's harm will deter cigarette consumption over the long run.

The images include tobacco-diseased lungs beside healthy lungs, a corpse in casket, a man exhaling smoke though a tracheostomy, and lip cancer. There are also several cartoons and photos of mothers blowing smoke into infants' faces. One positive image shows a burly man exposing a T-shirt saying, “I Quit.”

Blunt statements accompany each image, intended to drive home the messages that cigarette smoke not only directly harms the smoker, but the smokers' children and people in close proximity.

“The introduction of these warnings is expected to have a significant public health impact by decreasing the number of smokers, resulting in lives saved, increased life expectancy, and improved health status,” FDA officials said in a statement.

“Eliciting strong emotional and cognitive reactions to the graphic cigarette warning label enhances recall and processing of the health warning, which helps ensure that the warning is better processed, understood, and remembered,” the study said. “As attitudes and beliefs change, they eventually lead to changes in intentions to quit or start smoking and then later to lower smoking initiation and successful cessation. The time scale on which this behavior change process occurs is largely unknown in the context of the impact of exposure to graphic warning labels on smoking behaviors, but the effects on behavior change are unlikely to be immediate or short-term.”

Nevertheless, groups promoting antitobacco messages – including the American Heart Association – strongly believe that the warnings will enhance consumer education and change behavior.

“Undoubtedly, the new graphic health warnings will heighten awareness about the dangers of smoking and, more importantly, encourage smokers to quit and discourage smoking initiation,” an AHA press statement read. “We're confident that the new labels will move us closer to our goal of making the nation 100% smoke free.”

Any one of nine images must appear on cigarette packs by Oct. 22, 2012.

Source Courtesy U.S. Food and Drug Administration

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said at the annual meeting of the American Headache Society.

"You all know this is nothing new. You keep working to meet your patients’ needs while considering side effects, cost, effectiveness, and speed of onset." But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 Sept. 2 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

• Dissatisfaction with current acute treatment (assessed by the 3-item summary from the Patient Perception of Migraine Questionnaire).

• Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

• Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

• Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

• History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs. The mean body mass index also differed slightly. Among the control group, the mean BMI was 29 kg/m², compared with 30 in the group with one unmet need and 32 in the group with two or more unmet needs.

Headache days per month also varied between the groups. Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

Overall, 41% of those with episodic migraine reported having at least one unmet need; 26% reported one and 14% reported two or more.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

"When we looked at the three most frequently reported areas, we saw an interesting overlap," Dr. Buse said. "Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas."

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well-understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

The AMPP study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck.

Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said at the annual meeting of the American Headache Society.

"You all know this is nothing new. You keep working to meet your patients’ needs while considering side effects, cost, effectiveness, and speed of onset." But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 Sept. 2 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

• Dissatisfaction with current acute treatment (assessed by the 3-item summary from the Patient Perception of Migraine Questionnaire).

• Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

• Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

• Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

• History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs. The mean body mass index also differed slightly. Among the control group, the mean BMI was 29 kg/m², compared with 30 in the group with one unmet need and 32 in the group with two or more unmet needs.

Headache days per month also varied between the groups. Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

Overall, 41% of those with episodic migraine reported having at least one unmet need; 26% reported one and 14% reported two or more.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

"When we looked at the three most frequently reported areas, we saw an interesting overlap," Dr. Buse said. "Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas."

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well-understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

The AMPP study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck.

Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said at the annual meeting of the American Headache Society.

"You all know this is nothing new. You keep working to meet your patients’ needs while considering side effects, cost, effectiveness, and speed of onset." But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 Sept. 2 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

• Dissatisfaction with current acute treatment (assessed by the 3-item summary from the Patient Perception of Migraine Questionnaire).

• Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

• Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

• Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

• History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs. The mean body mass index also differed slightly. Among the control group, the mean BMI was 29 kg/m², compared with 30 in the group with one unmet need and 32 in the group with two or more unmet needs.

Headache days per month also varied between the groups. Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

Overall, 41% of those with episodic migraine reported having at least one unmet need; 26% reported one and 14% reported two or more.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

"When we looked at the three most frequently reported areas, we saw an interesting overlap," Dr. Buse said. "Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas."

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well-understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

The AMPP study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck.

Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said at the annual meeting of the American Headache Society.

"You all know this is nothing new. You keep working to meet your patients’ needs while considering side effects, cost, effectiveness, and speed of onset." But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 Sept. 2 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

• Dissatisfaction with current acute treatment (assessed by the 3-item summary from the Patient Perception of Migraine Questionnaire).

• Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

• Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

• Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

• History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs. The mean body mass index also differed slightly. Among the control group, the mean BMI was 29 kg/m², compared with 30 in the group with one unmet need and 32 in the group with two or more unmet needs.

Headache days per month also varied between the groups. Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

Overall, 41% of those with episodic migraine reported having at least one unmet need; 26% reported one and 14% reported two or more.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

"When we looked at the three most frequently reported areas, we saw an interesting overlap," Dr. Buse said. "Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas."

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well-understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

The AMPP study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck.

Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said at the annual meeting of the American Headache Society.

"You all know this is nothing new. You keep working to meet your patients’ needs while considering side effects, cost, effectiveness, and speed of onset." But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 Sept. 2 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

• Dissatisfaction with current acute treatment (assessed by the 3-item summary from the Patient Perception of Migraine Questionnaire).

• Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

• Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

• Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

• History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs. The mean body mass index also differed slightly. Among the control group, the mean BMI was 29 kg/m², compared with 30 in the group with one unmet need and 32 in the group with two or more unmet needs.

Headache days per month also varied between the groups. Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

Overall, 41% of those with episodic migraine reported having at least one unmet need; 26% reported one and 14% reported two or more.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

"When we looked at the three most frequently reported areas, we saw an interesting overlap," Dr. Buse said. "Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas."

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well-understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

The AMPP study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck.

Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.

WASHINGTON – Almost half of patients with episodic migraine report having at least one unmet medical need, according to the findings of more than 20,000 people participating in a population-based survey.

The findings suggest that despite the expanding armamentarium of acute migraine-specific therapies, patient satisfaction with treatment is at best low to moderate for many, Dawn Buse, Ph.D., said at the annual meeting of the American Headache Society.

"You all know this is nothing new. You keep working to meet your patients’ needs while considering side effects, cost, effectiveness, and speed of onset." But despite all these efforts, some patients report unsatisfactory results.

Dr. Buse, director of behavioral medicine at the Montefiore Headache Center, New York, and her colleagues examined data from the AMPP (American Migraine Prevalence and Prevention) study (Headache 2008 Sept. 2 [doi:10.1111/j.1526-4610.2008.01217.x]). This population-based survey began in 2004, when a general-population headache screening netted 162,756 respondents, 36,000 of whom reported having severe headache.

The study that was presented at the meeting examined data from the 2009 sample of 11,792 who had been followed since 2005, including 5,600 who met the International Classification of Headache Disorders definition of episodic migraine. A control group comprised 8,315 who were free of severe headache or migraine in the original 2004 survey.

Dr. Buse and her coinvestigators identified five domains of possible unmet treatment needs, and resurveyed the migraine population for their response. The domains included the following:

• Dissatisfaction with current acute treatment (assessed by the 3-item summary from the Patient Perception of Migraine Questionnaire).

• Moderate or severe headache-related disability (defined by a score of at least 11 on the Migraine Disability Assessment Test).

• Excessive use of opioids or barbiturates (that is, using the drugs at least 4 days per month or meeting the DSM-IV criteria for dependence).

• Excessive use of the emergency department or urgent care clinic for headache (that is, at least two visits in the preceding year).

• History of cardiovascular events that might preclude triptan therapy (including heart attack, stroke, angina, claudication, stent placement, or coronary artery bypass graft).

The samples were not significantly different in demographics; most (81%) were women. The mean age in the control group was 51 years vs. 52 years in the two groups with unmet needs. The mean body mass index also differed slightly. Among the control group, the mean BMI was 29 kg/m², compared with 30 in the group with one unmet need and 32 in the group with two or more unmet needs.

Headache days per month also varied between the groups. Those with no unmet needs reported a mean of 2 days per month with headache, compared with 3 days per month for the group with one unmet need, and 5 days per month for those with two or more needs.

Overall, 41% of those with episodic migraine reported having at least one unmet need; 26% reported one and 14% reported two or more.

The unmet need that was most commonly reported was headache-related disability of moderate to severe intensity (19%). Some 15% claimed dissatisfaction with their current therapy. Opioid or barbiturate use or dependence was seen in 13% of respondents. In all, 10% reported cardiovascular disease that could preclude triptan use, although 26% of these used the drugs despite these risks. Finally, 2% reported frequent headache-related visits to the ED or urgent care center.

"When we looked at the three most frequently reported areas, we saw an interesting overlap," Dr. Buse said. "Of the 19% who met the criteria for moderate to severe headache-related disability, 10% met that area only. But 4% of them also reported opioid overuse, 3% also reported dissatisfaction with their medications, and 2% endorsed all three of these areas."

The investigators then contrasted psychological comorbidities between the group with unmet needs and the 60% who reported no unmet needs. Anxiety and depression correlated significantly with the number of unmet needs.

Among the control group, 5% met criteria for anxiety and 10% for depression. Among the group with one unmet need, the rates were 11% for anxiety and 22% for depression. Among the group with at least two unmet needs, the rates were 21% for anxiety and 41% for depression.

In an interview, Dr. Buse said the relationship between headache and psychiatric disorders is not well-understood, but appears to be bidirectional. Anxiety increases the likelihood and the severity of headache, whereas headaches increase the risk of anxiety. The brain neurotransmitters that are involved in depression may also predispose a person to headache, but years of headache pain also increase the risk of becoming depressed, she said.

The AMPP study is funded by the American Headache Society through grants from Ortho-McNeil Neurologics and Merck Sharp & Dohme Corp., a subsidiary of Merck.

Dr. Buse has received research support from Allergan Pharmaceuticals, Iroko Pharmaceuticals, MAP Pharmaceuticals, and Merck.