Blood pressure should be checked at every prenatal visit to screen for preeclampsia, according to a new recommendation from the U.S. Preventive Services Task Force.

The USPSTF commissioned a review of the current literature to update its initial recommendation regarding preeclampsia screening, which was issued in 1996. The update was considered important “given changes to screening, diagnosis, and management practices, as well as population health, over the past two decades.”

However, the evidence regarding different screening approaches is still quite limited, and the USPSTF did not change its recommendation except to indicate blood pressure checks at every visit rather than “periodically.” The current advice is a “B” recommendation, meaning that the USPSTF recommends the service.

[email protected]

Blood pressure should be checked at every prenatal visit to screen for preeclampsia, according to a new recommendation from the U.S. Preventive Services Task Force.

The USPSTF commissioned a review of the current literature to update its initial recommendation regarding preeclampsia screening, which was issued in 1996. The update was considered important “given changes to screening, diagnosis, and management practices, as well as population health, over the past two decades.”

However, the evidence regarding different screening approaches is still quite limited, and the USPSTF did not change its recommendation except to indicate blood pressure checks at every visit rather than “periodically.” The current advice is a “B” recommendation, meaning that the USPSTF recommends the service.

[email protected]

Blood pressure should be checked at every prenatal visit to screen for preeclampsia, according to a new recommendation from the U.S. Preventive Services Task Force.

The USPSTF commissioned a review of the current literature to update its initial recommendation regarding preeclampsia screening, which was issued in 1996. The update was considered important “given changes to screening, diagnosis, and management practices, as well as population health, over the past two decades.”

However, the evidence regarding different screening approaches is still quite limited, and the USPSTF did not change its recommendation except to indicate blood pressure checks at every visit rather than “periodically.” The current advice is a “B” recommendation, meaning that the USPSTF recommends the service.

[email protected]

STOWE, VT—Mounting evidence suggests that gender affects the modulation of pain to a greater extent than has been understood, according to an overview presented at the 27th Annual Headache Cooperative of New England Stowe Headache Symposium. Data indicate that the differences are biologic, and researchers are examining whether social and psychologic differences also may influence pain.

“If biomedicine ever comes up with a treatment, reproductive issues aside, that works and gets approval for one sex and not the other for treating the same underlying condition, it is going to happen in pain first,” said Jeffrey S. Mogil, PhD, Canada Research Chair in Genetics of Pain at McGill University in Montreal. “Maybe we are only 10 or 15 years away from seeing such a thing occur.”

A Clear Gender Difference

The first investigation of gender differences in pain was published in 1997, according to Dr. Mogil. It indicated that a greater number of chronic pain syndromes were more prevalent in women, compared with those that were more prevalent in men. Furthermore, the syndromes that were more prevalent in women were more common overall. The study also estimated that approximately 70% of patients with chronic pain are women. This result, however, could follow from reluctance among men to consult a physician, said Dr. Mogil.

When Dr. Mogil reviewed epidemiologic studies of pain, he found that women were between 5% and 10% more likely than men to endorse the symptoms of chronic pain. Although the studies used different definitions of chronic pain, each study used the same definition for men and women. A possible explanation for the result is that women are more susceptible to painful diseases.

But when he examined laboratory data from controlled experiments involving painful stimuli, Dr. Mogil found that “regardless of what type of pain you are looking at, and regardless of how it is measured, women are more sensitive to pain than men.” The difference in pain sensitivity is not great and depends on various factors, but it is clear and unmistakable, he added.

Biology Influences Pain Sensitivity

Biologic differences may explain gender differences in pain sensitivity. Research during the past 20 years has suggested that microglia play an important role in nociception. Newer data, however, indicate that microglial involvement in pain may be specific to males. Because the majority of animal research had been performed in male rodents, this observation had not been made previously, said Dr. Mogil.

He and his colleagues injured male and female mice to induce mechanical allodynia. The mice exhibited the same amount of mechanical allodynia, regardless of gender. The investigators next administered minocycline, a glial inhibitor, to the mice. The intervention reversed the allodynia in male mice, but not in female mice. Using fluorocitrate or propentofylline in place of minocycline produces the same result, said Dr. Mogil. Research into the biologic basis for pain modulation in females is ongoing.

Gender, Stress, and Analgesia

A patient’s sensitivity to pain may be influenced not only by his or her gender, but also by the gender of a person that the patient encounters. The results of certain mouse studies prompted researchers to hypothesize that the experimenters themselves may have produced analgesia, and Dr. Mogil decided to test this hypothesis.

When an investigator injected zymosan, an inflammatory agent, into a mouse’s ankle and left the room, the injection caused pain and grimacing in the mouse. When a male investigator administered zymosan to a mouse and remained in the room, the rate of grimacing decreased by approximately 40%. “In fact, experimenters are causing analgesia,” said Dr. Mogil. A female investigator did not produce the same effect, however.

Further research indicated that the effect has an olfactory origin. When injured mice are exposed to clothing previously worn by a male, or to bedding previously used by any male animal, they exhibit the same reduction in pain. “This is a stress phenomenon,” said Dr. Mogil. A mouse’s level of corticosterone, an equivalent to cortisol in humans, increases after exposure to male experimenters or their clothing.

The mice appear to be responding to axillary chemosignals (eg, androstadienone and androstenone) that males emit. The most important compound may be 3-Methyl-2-hexenoic acid, because it is “the only chemosignal that can produce this effect at reasonable concentrations in the nanomolar range,” said Dr. Mogil. He and his colleagues are studying whether these chemosignals produce the same responses in humans. “I would expect the effect to be much smaller and last for not quite as long,” he said. They also are studying the social modulation of pain in animals and humans.

—Erik Greb

Suggested Reading

Berkley KJ. Sex differences in pain. Behav Brain Sci. 1997;20(3):371-380; discussion 435-513.

Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13(12):859-866.

Sorge RE, Mapplebeck JC, Rosen S, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18(8):1081-1083.

Sorge RE, Martin LJ, Isbester KA, et al. Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nat Methods. 2014;11(6):629-632.

STOWE, VT—Mounting evidence suggests that gender affects the modulation of pain to a greater extent than has been understood, according to an overview presented at the 27th Annual Headache Cooperative of New England Stowe Headache Symposium. Data indicate that the differences are biologic, and researchers are examining whether social and psychologic differences also may influence pain.

“If biomedicine ever comes up with a treatment, reproductive issues aside, that works and gets approval for one sex and not the other for treating the same underlying condition, it is going to happen in pain first,” said Jeffrey S. Mogil, PhD, Canada Research Chair in Genetics of Pain at McGill University in Montreal. “Maybe we are only 10 or 15 years away from seeing such a thing occur.”

A Clear Gender Difference

The first investigation of gender differences in pain was published in 1997, according to Dr. Mogil. It indicated that a greater number of chronic pain syndromes were more prevalent in women, compared with those that were more prevalent in men. Furthermore, the syndromes that were more prevalent in women were more common overall. The study also estimated that approximately 70% of patients with chronic pain are women. This result, however, could follow from reluctance among men to consult a physician, said Dr. Mogil.

When Dr. Mogil reviewed epidemiologic studies of pain, he found that women were between 5% and 10% more likely than men to endorse the symptoms of chronic pain. Although the studies used different definitions of chronic pain, each study used the same definition for men and women. A possible explanation for the result is that women are more susceptible to painful diseases.

But when he examined laboratory data from controlled experiments involving painful stimuli, Dr. Mogil found that “regardless of what type of pain you are looking at, and regardless of how it is measured, women are more sensitive to pain than men.” The difference in pain sensitivity is not great and depends on various factors, but it is clear and unmistakable, he added.

Biology Influences Pain Sensitivity

Biologic differences may explain gender differences in pain sensitivity. Research during the past 20 years has suggested that microglia play an important role in nociception. Newer data, however, indicate that microglial involvement in pain may be specific to males. Because the majority of animal research had been performed in male rodents, this observation had not been made previously, said Dr. Mogil.

He and his colleagues injured male and female mice to induce mechanical allodynia. The mice exhibited the same amount of mechanical allodynia, regardless of gender. The investigators next administered minocycline, a glial inhibitor, to the mice. The intervention reversed the allodynia in male mice, but not in female mice. Using fluorocitrate or propentofylline in place of minocycline produces the same result, said Dr. Mogil. Research into the biologic basis for pain modulation in females is ongoing.

Gender, Stress, and Analgesia

A patient’s sensitivity to pain may be influenced not only by his or her gender, but also by the gender of a person that the patient encounters. The results of certain mouse studies prompted researchers to hypothesize that the experimenters themselves may have produced analgesia, and Dr. Mogil decided to test this hypothesis.

When an investigator injected zymosan, an inflammatory agent, into a mouse’s ankle and left the room, the injection caused pain and grimacing in the mouse. When a male investigator administered zymosan to a mouse and remained in the room, the rate of grimacing decreased by approximately 40%. “In fact, experimenters are causing analgesia,” said Dr. Mogil. A female investigator did not produce the same effect, however.

Further research indicated that the effect has an olfactory origin. When injured mice are exposed to clothing previously worn by a male, or to bedding previously used by any male animal, they exhibit the same reduction in pain. “This is a stress phenomenon,” said Dr. Mogil. A mouse’s level of corticosterone, an equivalent to cortisol in humans, increases after exposure to male experimenters or their clothing.

The mice appear to be responding to axillary chemosignals (eg, androstadienone and androstenone) that males emit. The most important compound may be 3-Methyl-2-hexenoic acid, because it is “the only chemosignal that can produce this effect at reasonable concentrations in the nanomolar range,” said Dr. Mogil. He and his colleagues are studying whether these chemosignals produce the same responses in humans. “I would expect the effect to be much smaller and last for not quite as long,” he said. They also are studying the social modulation of pain in animals and humans.

—Erik Greb

Suggested Reading

Berkley KJ. Sex differences in pain. Behav Brain Sci. 1997;20(3):371-380; discussion 435-513.

Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13(12):859-866.

Sorge RE, Mapplebeck JC, Rosen S, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18(8):1081-1083.

Sorge RE, Martin LJ, Isbester KA, et al. Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nat Methods. 2014;11(6):629-632.

STOWE, VT—Mounting evidence suggests that gender affects the modulation of pain to a greater extent than has been understood, according to an overview presented at the 27th Annual Headache Cooperative of New England Stowe Headache Symposium. Data indicate that the differences are biologic, and researchers are examining whether social and psychologic differences also may influence pain.

“If biomedicine ever comes up with a treatment, reproductive issues aside, that works and gets approval for one sex and not the other for treating the same underlying condition, it is going to happen in pain first,” said Jeffrey S. Mogil, PhD, Canada Research Chair in Genetics of Pain at McGill University in Montreal. “Maybe we are only 10 or 15 years away from seeing such a thing occur.”

A Clear Gender Difference

The first investigation of gender differences in pain was published in 1997, according to Dr. Mogil. It indicated that a greater number of chronic pain syndromes were more prevalent in women, compared with those that were more prevalent in men. Furthermore, the syndromes that were more prevalent in women were more common overall. The study also estimated that approximately 70% of patients with chronic pain are women. This result, however, could follow from reluctance among men to consult a physician, said Dr. Mogil.

When Dr. Mogil reviewed epidemiologic studies of pain, he found that women were between 5% and 10% more likely than men to endorse the symptoms of chronic pain. Although the studies used different definitions of chronic pain, each study used the same definition for men and women. A possible explanation for the result is that women are more susceptible to painful diseases.

But when he examined laboratory data from controlled experiments involving painful stimuli, Dr. Mogil found that “regardless of what type of pain you are looking at, and regardless of how it is measured, women are more sensitive to pain than men.” The difference in pain sensitivity is not great and depends on various factors, but it is clear and unmistakable, he added.

Biology Influences Pain Sensitivity

Biologic differences may explain gender differences in pain sensitivity. Research during the past 20 years has suggested that microglia play an important role in nociception. Newer data, however, indicate that microglial involvement in pain may be specific to males. Because the majority of animal research had been performed in male rodents, this observation had not been made previously, said Dr. Mogil.

He and his colleagues injured male and female mice to induce mechanical allodynia. The mice exhibited the same amount of mechanical allodynia, regardless of gender. The investigators next administered minocycline, a glial inhibitor, to the mice. The intervention reversed the allodynia in male mice, but not in female mice. Using fluorocitrate or propentofylline in place of minocycline produces the same result, said Dr. Mogil. Research into the biologic basis for pain modulation in females is ongoing.

Gender, Stress, and Analgesia

A patient’s sensitivity to pain may be influenced not only by his or her gender, but also by the gender of a person that the patient encounters. The results of certain mouse studies prompted researchers to hypothesize that the experimenters themselves may have produced analgesia, and Dr. Mogil decided to test this hypothesis.

When an investigator injected zymosan, an inflammatory agent, into a mouse’s ankle and left the room, the injection caused pain and grimacing in the mouse. When a male investigator administered zymosan to a mouse and remained in the room, the rate of grimacing decreased by approximately 40%. “In fact, experimenters are causing analgesia,” said Dr. Mogil. A female investigator did not produce the same effect, however.

Further research indicated that the effect has an olfactory origin. When injured mice are exposed to clothing previously worn by a male, or to bedding previously used by any male animal, they exhibit the same reduction in pain. “This is a stress phenomenon,” said Dr. Mogil. A mouse’s level of corticosterone, an equivalent to cortisol in humans, increases after exposure to male experimenters or their clothing.

The mice appear to be responding to axillary chemosignals (eg, androstadienone and androstenone) that males emit. The most important compound may be 3-Methyl-2-hexenoic acid, because it is “the only chemosignal that can produce this effect at reasonable concentrations in the nanomolar range,” said Dr. Mogil. He and his colleagues are studying whether these chemosignals produce the same responses in humans. “I would expect the effect to be much smaller and last for not quite as long,” he said. They also are studying the social modulation of pain in animals and humans.

—Erik Greb

Suggested Reading

Berkley KJ. Sex differences in pain. Behav Brain Sci. 1997;20(3):371-380; discussion 435-513.

Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13(12):859-866.

Sorge RE, Mapplebeck JC, Rosen S, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18(8):1081-1083.

Sorge RE, Martin LJ, Isbester KA, et al. Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nat Methods. 2014;11(6):629-632.

BOSTON – Intrathecal, autologous mesenchymal stem cell (MSC) treatment provided encouraging results for modifying the disease course of multiple system atrophy with relative safety and tolerability in a phase I/II trial.

The efficacy of MSCs on slowing multiple system atrophy (MSA) progression in a small trial of 24 patients appeared to be dependent on the dose, and, in the highest dose individuals, had a painful implantation response, trial investigator Wolfgang Singer, MD, reported at the annual meeting of the American Academy of Neurology.

Dr. Singer and his colleagues at the Mayo Clinic in Rochester, Minn., chose to investigate MSCs as a treatment because they are multipotent and capable of differentiating into different cell types, including glial cells, and they secrete neurotrophic factors, such as brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, which are thought to occur at pathologically low levels in individuals with MSA. The intrinsic immunomodulatory action of MSCs may also contribute to a potential benefit on neuroinflammatory aspects of MSA pathology.

MSCs have previously shown promising results on slowing disease progression in an open-label study of Korean patients with MSA, who received an intra-arterial infusion of MSCs into the internal carotids and dominant vertebral artery, followed by intravenous infusions (Clin Pharmacol Ther. 2008 May;83[5]:723-30). Those results were confirmed in a double-blind, placebo-controlled study (Ann Neurol. 2012 Jul;72[1]:32-40), but evidence of microemboli raised concerns with the Mayo Clinic team about stroke risk with the intra-arterial approach, Dr. Singer said.

The intrathecal route of administration also may be advantageous over an intra-arterial approach by reaching the targets of MSCs in the brain “in a more widespread fashion,” Dr. Singer said.

The relative safety and hint of efficacy with the different route of MSC administration in the Mayo Clinic study make it “a really groundbreaking direction to take,” session comoderator Christopher H. Gibbons, MD, said in an interview. “I think this a very good, small, but critical, step in demonstrating that ... you can do this, and maybe there’s a signal that it is, in fact, working at slowing down disease progression, which I think is incredibly important in this disease.”

In the current study, Dr. Singer and his associates intrathecally administered between 10 and 200 million autologous, fat-derived MSCs via lumbar puncture in predefined dose tiers and then followed patients over 1 year. Overall, 8 patients received a single dose of 10 million cells, 12 received a dose of 50 million cells followed by a second 50-million cell dose 4 weeks later, and 4 received a dose of 100 million cells followed by a second 100-million cell dose 4 weeks later.

The 24 patients in the study all met consensus criteria for probable MSA, had at least moderate laboratory evidence of autonomic failure, and were at an early stage of disease with a Unified MSA Rating Scale part 1 score of 18 or less.

In the primary outcome of safety, the investigators reported no treatment–attributable serious adverse events and said that the treatment was generally well-tolerated. All 16 patients who took either the high or medium doses had MRI abnormalities that showed thickening/enhancement of cauda equina nerve roots at the level of the puncture that were asymptomatic and did not lead to neurologic deficits.

The 12 medium-dose patients had variable elevation of cerebrospinal fluid protein and cell counts, and 5 had mild and transient low back pain. In the highest-dose tier, three of four patients developed low back pain, some of which was severe, and the same MRI findings, which signaled to the investigators that a dose-limiting toxicity had been reached.

Some patients also reported headaches after lumbar punctures, which were expected. Two patients also developed mild febrile reactions after administrations that were self-limited.

Treatment with MSCs led to a significantly lower rate of disease progression as measured by total score on the Unified MSA Rating Scale (0.43 vs. 1.22 points/month; P = .009), and this difference was even greater for the medium-dose tier than for the low-dose tier. The investigators used the placebo group from their recently completed rifampicin treatment trial in MSA to make the efficacy assessment.

There was no change between the treatment groups and the historical control group on the Composite Autonomic Symptom Scale or the Composite Autonomic Severity Score from baseline to 1 year.

Based on the promising findings, the Food and Drug Administration granted permission for a compassionate extension study for apparent responders to receive additional injections every 6 months, and, so far, 16 patients have been reinjected, according to Dr. Singer.

Dr. Singer and his associates have used these results as the basis for a multicenter, double-blind, placebo-controlled phase II/III study that is in the late planning stages. This kind of trial will be important for determining whether it’s possible to hold the quality of the MSC treatment steady and get the same sort of response across many centers, said Dr. Gibbons, a clinical neurophysiologist at Beth Israel Deaconess Medical Center, Boston, and past-president of the American Autonomic Society.

The trial was supported by grants from the National Institutes of Health, the Cure MSA Foundation, the Food and Drug Administration, the Autonomic Rare Disease Consortium, and Mayo Clinic funds. Dr. Singer and Dr. Gibbons reported having no relevant financial disclosures.

You can watch a video interview with Dr. Singer here.

Vidyard Video

 

 

[email protected]

BOSTON – Intrathecal, autologous mesenchymal stem cell (MSC) treatment provided encouraging results for modifying the disease course of multiple system atrophy with relative safety and tolerability in a phase I/II trial.

The efficacy of MSCs on slowing multiple system atrophy (MSA) progression in a small trial of 24 patients appeared to be dependent on the dose, and, in the highest dose individuals, had a painful implantation response, trial investigator Wolfgang Singer, MD, reported at the annual meeting of the American Academy of Neurology.

Dr. Singer and his colleagues at the Mayo Clinic in Rochester, Minn., chose to investigate MSCs as a treatment because they are multipotent and capable of differentiating into different cell types, including glial cells, and they secrete neurotrophic factors, such as brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, which are thought to occur at pathologically low levels in individuals with MSA. The intrinsic immunomodulatory action of MSCs may also contribute to a potential benefit on neuroinflammatory aspects of MSA pathology.

MSCs have previously shown promising results on slowing disease progression in an open-label study of Korean patients with MSA, who received an intra-arterial infusion of MSCs into the internal carotids and dominant vertebral artery, followed by intravenous infusions (Clin Pharmacol Ther. 2008 May;83[5]:723-30). Those results were confirmed in a double-blind, placebo-controlled study (Ann Neurol. 2012 Jul;72[1]:32-40), but evidence of microemboli raised concerns with the Mayo Clinic team about stroke risk with the intra-arterial approach, Dr. Singer said.

The intrathecal route of administration also may be advantageous over an intra-arterial approach by reaching the targets of MSCs in the brain “in a more widespread fashion,” Dr. Singer said.

The relative safety and hint of efficacy with the different route of MSC administration in the Mayo Clinic study make it “a really groundbreaking direction to take,” session comoderator Christopher H. Gibbons, MD, said in an interview. “I think this a very good, small, but critical, step in demonstrating that ... you can do this, and maybe there’s a signal that it is, in fact, working at slowing down disease progression, which I think is incredibly important in this disease.”

In the current study, Dr. Singer and his associates intrathecally administered between 10 and 200 million autologous, fat-derived MSCs via lumbar puncture in predefined dose tiers and then followed patients over 1 year. Overall, 8 patients received a single dose of 10 million cells, 12 received a dose of 50 million cells followed by a second 50-million cell dose 4 weeks later, and 4 received a dose of 100 million cells followed by a second 100-million cell dose 4 weeks later.

The 24 patients in the study all met consensus criteria for probable MSA, had at least moderate laboratory evidence of autonomic failure, and were at an early stage of disease with a Unified MSA Rating Scale part 1 score of 18 or less.

In the primary outcome of safety, the investigators reported no treatment–attributable serious adverse events and said that the treatment was generally well-tolerated. All 16 patients who took either the high or medium doses had MRI abnormalities that showed thickening/enhancement of cauda equina nerve roots at the level of the puncture that were asymptomatic and did not lead to neurologic deficits.

The 12 medium-dose patients had variable elevation of cerebrospinal fluid protein and cell counts, and 5 had mild and transient low back pain. In the highest-dose tier, three of four patients developed low back pain, some of which was severe, and the same MRI findings, which signaled to the investigators that a dose-limiting toxicity had been reached.

Some patients also reported headaches after lumbar punctures, which were expected. Two patients also developed mild febrile reactions after administrations that were self-limited.

Treatment with MSCs led to a significantly lower rate of disease progression as measured by total score on the Unified MSA Rating Scale (0.43 vs. 1.22 points/month; P = .009), and this difference was even greater for the medium-dose tier than for the low-dose tier. The investigators used the placebo group from their recently completed rifampicin treatment trial in MSA to make the efficacy assessment.

There was no change between the treatment groups and the historical control group on the Composite Autonomic Symptom Scale or the Composite Autonomic Severity Score from baseline to 1 year.

Based on the promising findings, the Food and Drug Administration granted permission for a compassionate extension study for apparent responders to receive additional injections every 6 months, and, so far, 16 patients have been reinjected, according to Dr. Singer.

Dr. Singer and his associates have used these results as the basis for a multicenter, double-blind, placebo-controlled phase II/III study that is in the late planning stages. This kind of trial will be important for determining whether it’s possible to hold the quality of the MSC treatment steady and get the same sort of response across many centers, said Dr. Gibbons, a clinical neurophysiologist at Beth Israel Deaconess Medical Center, Boston, and past-president of the American Autonomic Society.

The trial was supported by grants from the National Institutes of Health, the Cure MSA Foundation, the Food and Drug Administration, the Autonomic Rare Disease Consortium, and Mayo Clinic funds. Dr. Singer and Dr. Gibbons reported having no relevant financial disclosures.

You can watch a video interview with Dr. Singer here.

Vidyard Video

 

 

[email protected]

BOSTON – Intrathecal, autologous mesenchymal stem cell (MSC) treatment provided encouraging results for modifying the disease course of multiple system atrophy with relative safety and tolerability in a phase I/II trial.

The efficacy of MSCs on slowing multiple system atrophy (MSA) progression in a small trial of 24 patients appeared to be dependent on the dose, and, in the highest dose individuals, had a painful implantation response, trial investigator Wolfgang Singer, MD, reported at the annual meeting of the American Academy of Neurology.

Dr. Singer and his colleagues at the Mayo Clinic in Rochester, Minn., chose to investigate MSCs as a treatment because they are multipotent and capable of differentiating into different cell types, including glial cells, and they secrete neurotrophic factors, such as brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, which are thought to occur at pathologically low levels in individuals with MSA. The intrinsic immunomodulatory action of MSCs may also contribute to a potential benefit on neuroinflammatory aspects of MSA pathology.

MSCs have previously shown promising results on slowing disease progression in an open-label study of Korean patients with MSA, who received an intra-arterial infusion of MSCs into the internal carotids and dominant vertebral artery, followed by intravenous infusions (Clin Pharmacol Ther. 2008 May;83[5]:723-30). Those results were confirmed in a double-blind, placebo-controlled study (Ann Neurol. 2012 Jul;72[1]:32-40), but evidence of microemboli raised concerns with the Mayo Clinic team about stroke risk with the intra-arterial approach, Dr. Singer said.

The intrathecal route of administration also may be advantageous over an intra-arterial approach by reaching the targets of MSCs in the brain “in a more widespread fashion,” Dr. Singer said.

The relative safety and hint of efficacy with the different route of MSC administration in the Mayo Clinic study make it “a really groundbreaking direction to take,” session comoderator Christopher H. Gibbons, MD, said in an interview. “I think this a very good, small, but critical, step in demonstrating that ... you can do this, and maybe there’s a signal that it is, in fact, working at slowing down disease progression, which I think is incredibly important in this disease.”

In the current study, Dr. Singer and his associates intrathecally administered between 10 and 200 million autologous, fat-derived MSCs via lumbar puncture in predefined dose tiers and then followed patients over 1 year. Overall, 8 patients received a single dose of 10 million cells, 12 received a dose of 50 million cells followed by a second 50-million cell dose 4 weeks later, and 4 received a dose of 100 million cells followed by a second 100-million cell dose 4 weeks later.

The 24 patients in the study all met consensus criteria for probable MSA, had at least moderate laboratory evidence of autonomic failure, and were at an early stage of disease with a Unified MSA Rating Scale part 1 score of 18 or less.

In the primary outcome of safety, the investigators reported no treatment–attributable serious adverse events and said that the treatment was generally well-tolerated. All 16 patients who took either the high or medium doses had MRI abnormalities that showed thickening/enhancement of cauda equina nerve roots at the level of the puncture that were asymptomatic and did not lead to neurologic deficits.

The 12 medium-dose patients had variable elevation of cerebrospinal fluid protein and cell counts, and 5 had mild and transient low back pain. In the highest-dose tier, three of four patients developed low back pain, some of which was severe, and the same MRI findings, which signaled to the investigators that a dose-limiting toxicity had been reached.

Some patients also reported headaches after lumbar punctures, which were expected. Two patients also developed mild febrile reactions after administrations that were self-limited.

Treatment with MSCs led to a significantly lower rate of disease progression as measured by total score on the Unified MSA Rating Scale (0.43 vs. 1.22 points/month; P = .009), and this difference was even greater for the medium-dose tier than for the low-dose tier. The investigators used the placebo group from their recently completed rifampicin treatment trial in MSA to make the efficacy assessment.

There was no change between the treatment groups and the historical control group on the Composite Autonomic Symptom Scale or the Composite Autonomic Severity Score from baseline to 1 year.

Based on the promising findings, the Food and Drug Administration granted permission for a compassionate extension study for apparent responders to receive additional injections every 6 months, and, so far, 16 patients have been reinjected, according to Dr. Singer.

Dr. Singer and his associates have used these results as the basis for a multicenter, double-blind, placebo-controlled phase II/III study that is in the late planning stages. This kind of trial will be important for determining whether it’s possible to hold the quality of the MSC treatment steady and get the same sort of response across many centers, said Dr. Gibbons, a clinical neurophysiologist at Beth Israel Deaconess Medical Center, Boston, and past-president of the American Autonomic Society.

The trial was supported by grants from the National Institutes of Health, the Cure MSA Foundation, the Food and Drug Administration, the Autonomic Rare Disease Consortium, and Mayo Clinic funds. Dr. Singer and Dr. Gibbons reported having no relevant financial disclosures.

You can watch a video interview with Dr. Singer here.

Vidyard Video

 

 

[email protected]

Recently North Carolina proposed a bill (House Bill 780) that will ban same-sex marriage in the state, even though the U.S. Supreme Court ruled in 2015 that no states can ban same-sex marriage because doing so violates the 14th Amendment. Although many mainly will argue that H.B. 780 is unconstitutional, this bill also can be detrimental to the health of lesbian, gay, and bisexual (LGB) youth.

In March 2017, JAMA Pediatrics published a study on the association between same-sex marriage laws and the rates of suicide attempts.¹ Using data from the Youth Risk Behavior Surveillance System, they analyzed the relationship between state policies that permitted same-sex marriage and self-report of suicide attempts within the last 12 months. Thirty percent of LGB youth (13% of the survey population) reported a suicide attempt in the past year prior to any state policies that permitted same-sex marriage, compared with about 9% of the general population. After states implemented pro–same-sex marriage policies, LGB youth suicide attempts dropped to about 26% – a 14% relative decline. This was not limited to LGB youth. The general youth suicide rates declined from 8.6% to 8% – a 7% relative decline. Although the change in suicide attempts was small, the authors determined that the likelihood it occurred by chance was very slim, and concluded that policies enabling same-sex marriage may be associated with an improvement in population health, especially for LGB youth.

This was not the first study examining the relationship between policies and the health of LGB youth. Mark Hatzenbuehler, PhD, of Columbia University, New York, and his associates have published multiple studies on this topic. Four years earlier, Hatzenbuehler et al. published a study on the relationship between antibullying policies and suicide among LGB youth. Using data from the Oregon Healthy Teen survey (2006-2008), he found that LGB youth who live in counties where there are fewer districts with antibullying policies are more than twice as likely to attempt suicide, compared with LGB youth who live in counties where more districts had antibullying policies. Furthermore, the type of antibullying policy mattered. If a district’s antibullying policy did not prohibit bullying based on sexual orientation, then it had no impact on the suicide attempt rates of LGB youth in that area.² Similar results were found when the relationship between anti–homophobic bullying policies and LGB suicide attempts was examined in the larger Youth Risk Behavior Surveillance System.³

State and local policies also influence other health outcomes among LGB youth. Hatzenbuehler et al. did another study that examined community-level determinants of tobacco use among LGB youth. Again using the data from the Oregon Healthy Teen Survey, they found that LGB youth living in communities that were more supportive of LGB youth (i.e., communities with a high proportion of same-sex couples living in the area, a high proportion of gay-straight alliances at schools, and LGB-specific antibullying policies) were less likely to smoke cigarettes, compared with LGB youth living in communities that were less supportive.⁴ A similar study in Canada by Konishi et al. found that schools with gay-straight alliances and anti–homophobic bullying policies were less likely to have LGB youth engaging in risky alcohol or illicit drug use.⁵

Why do these policies matter? A common theme among these policies is that they can either cause or alleviate stress for LGB youth. States that restrict same-sex marriages or schools that do not have any gay-straight alliances may signal to LGB youth that they are not valued or welcomed, or at the very worse, are despised. This creates a hostile and stressful environment for LGB youth, which raises the risk for mental health problems, such as depression and anxiety, which in turn, raises the risk for substance use and suicide.⁶ Conversely, the presence of a gay-straight alliance at school or a state that allows same-sex marriage may indicate to LGB youth that they are welcomed, if not just tolerated, and may alleviate this risk. Furthermore, antibullying policies seem to reduce the stress associated with bullying among LGB youth because it may serve as a deterrent to bullying based on sexual orientation. Although passing pro-LGB policies will not solve all the health problems among LGB youth, these policies certainly have an impact.

There might be trepidation among some pediatricians about being vocal on a politically charged policy proposal such as H.B. 780. However, suicide and substance use are major concerns for all physicians – especially pediatricians. Policy makers considering passing laws that can affect their LGB constituents should read these studies to see what kind of influence these proposals can have on the health and well-being of LGB youth. Moreover, health care providers should use their expertise, influence, and standing in their community to support policies that encourage protection for LGB youth and oppose policies that can harm LGB youth. These leaders are responsible for ensuring the health of the people they serve.
 

Dr. Montano is clinical instructor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC.

References

1. JAMA Pediatr. 2017. doi: 10.1001/jamapediatrics.2016.4529.

2. J Adolesc Health. 2013:S21-6. doi: 10.1016/j.jadohealth.2012.08.010.

3. Am J Public Health. 2014. doi: 10.2105/AJPH.2013.301508.

4. Arch Pediatr Adolesc Med. 2011. doi: 10.1001/archpediatrics.2011.64.

5. Prev Med. 2013. doi: 10.1016/j.ypmed.2013.06.031.

6. Psychol Bull. 2003. doi: 10.1037/0033-2909.129.5.674.

Recently North Carolina proposed a bill (House Bill 780) that will ban same-sex marriage in the state, even though the U.S. Supreme Court ruled in 2015 that no states can ban same-sex marriage because doing so violates the 14th Amendment. Although many mainly will argue that H.B. 780 is unconstitutional, this bill also can be detrimental to the health of lesbian, gay, and bisexual (LGB) youth.

In March 2017, JAMA Pediatrics published a study on the association between same-sex marriage laws and the rates of suicide attempts.¹ Using data from the Youth Risk Behavior Surveillance System, they analyzed the relationship between state policies that permitted same-sex marriage and self-report of suicide attempts within the last 12 months. Thirty percent of LGB youth (13% of the survey population) reported a suicide attempt in the past year prior to any state policies that permitted same-sex marriage, compared with about 9% of the general population. After states implemented pro–same-sex marriage policies, LGB youth suicide attempts dropped to about 26% – a 14% relative decline. This was not limited to LGB youth. The general youth suicide rates declined from 8.6% to 8% – a 7% relative decline. Although the change in suicide attempts was small, the authors determined that the likelihood it occurred by chance was very slim, and concluded that policies enabling same-sex marriage may be associated with an improvement in population health, especially for LGB youth.

This was not the first study examining the relationship between policies and the health of LGB youth. Mark Hatzenbuehler, PhD, of Columbia University, New York, and his associates have published multiple studies on this topic. Four years earlier, Hatzenbuehler et al. published a study on the relationship between antibullying policies and suicide among LGB youth. Using data from the Oregon Healthy Teen survey (2006-2008), he found that LGB youth who live in counties where there are fewer districts with antibullying policies are more than twice as likely to attempt suicide, compared with LGB youth who live in counties where more districts had antibullying policies. Furthermore, the type of antibullying policy mattered. If a district’s antibullying policy did not prohibit bullying based on sexual orientation, then it had no impact on the suicide attempt rates of LGB youth in that area.² Similar results were found when the relationship between anti–homophobic bullying policies and LGB suicide attempts was examined in the larger Youth Risk Behavior Surveillance System.³

State and local policies also influence other health outcomes among LGB youth. Hatzenbuehler et al. did another study that examined community-level determinants of tobacco use among LGB youth. Again using the data from the Oregon Healthy Teen Survey, they found that LGB youth living in communities that were more supportive of LGB youth (i.e., communities with a high proportion of same-sex couples living in the area, a high proportion of gay-straight alliances at schools, and LGB-specific antibullying policies) were less likely to smoke cigarettes, compared with LGB youth living in communities that were less supportive.⁴ A similar study in Canada by Konishi et al. found that schools with gay-straight alliances and anti–homophobic bullying policies were less likely to have LGB youth engaging in risky alcohol or illicit drug use.⁵

Why do these policies matter? A common theme among these policies is that they can either cause or alleviate stress for LGB youth. States that restrict same-sex marriages or schools that do not have any gay-straight alliances may signal to LGB youth that they are not valued or welcomed, or at the very worse, are despised. This creates a hostile and stressful environment for LGB youth, which raises the risk for mental health problems, such as depression and anxiety, which in turn, raises the risk for substance use and suicide.⁶ Conversely, the presence of a gay-straight alliance at school or a state that allows same-sex marriage may indicate to LGB youth that they are welcomed, if not just tolerated, and may alleviate this risk. Furthermore, antibullying policies seem to reduce the stress associated with bullying among LGB youth because it may serve as a deterrent to bullying based on sexual orientation. Although passing pro-LGB policies will not solve all the health problems among LGB youth, these policies certainly have an impact.

There might be trepidation among some pediatricians about being vocal on a politically charged policy proposal such as H.B. 780. However, suicide and substance use are major concerns for all physicians – especially pediatricians. Policy makers considering passing laws that can affect their LGB constituents should read these studies to see what kind of influence these proposals can have on the health and well-being of LGB youth. Moreover, health care providers should use their expertise, influence, and standing in their community to support policies that encourage protection for LGB youth and oppose policies that can harm LGB youth. These leaders are responsible for ensuring the health of the people they serve.
 

Dr. Montano is clinical instructor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC.

References

1. JAMA Pediatr. 2017. doi: 10.1001/jamapediatrics.2016.4529.

2. J Adolesc Health. 2013:S21-6. doi: 10.1016/j.jadohealth.2012.08.010.

3. Am J Public Health. 2014. doi: 10.2105/AJPH.2013.301508.

4. Arch Pediatr Adolesc Med. 2011. doi: 10.1001/archpediatrics.2011.64.

5. Prev Med. 2013. doi: 10.1016/j.ypmed.2013.06.031.

6. Psychol Bull. 2003. doi: 10.1037/0033-2909.129.5.674.

Recently North Carolina proposed a bill (House Bill 780) that will ban same-sex marriage in the state, even though the U.S. Supreme Court ruled in 2015 that no states can ban same-sex marriage because doing so violates the 14th Amendment. Although many mainly will argue that H.B. 780 is unconstitutional, this bill also can be detrimental to the health of lesbian, gay, and bisexual (LGB) youth.

In March 2017, JAMA Pediatrics published a study on the association between same-sex marriage laws and the rates of suicide attempts.¹ Using data from the Youth Risk Behavior Surveillance System, they analyzed the relationship between state policies that permitted same-sex marriage and self-report of suicide attempts within the last 12 months. Thirty percent of LGB youth (13% of the survey population) reported a suicide attempt in the past year prior to any state policies that permitted same-sex marriage, compared with about 9% of the general population. After states implemented pro–same-sex marriage policies, LGB youth suicide attempts dropped to about 26% – a 14% relative decline. This was not limited to LGB youth. The general youth suicide rates declined from 8.6% to 8% – a 7% relative decline. Although the change in suicide attempts was small, the authors determined that the likelihood it occurred by chance was very slim, and concluded that policies enabling same-sex marriage may be associated with an improvement in population health, especially for LGB youth.

This was not the first study examining the relationship between policies and the health of LGB youth. Mark Hatzenbuehler, PhD, of Columbia University, New York, and his associates have published multiple studies on this topic. Four years earlier, Hatzenbuehler et al. published a study on the relationship between antibullying policies and suicide among LGB youth. Using data from the Oregon Healthy Teen survey (2006-2008), he found that LGB youth who live in counties where there are fewer districts with antibullying policies are more than twice as likely to attempt suicide, compared with LGB youth who live in counties where more districts had antibullying policies. Furthermore, the type of antibullying policy mattered. If a district’s antibullying policy did not prohibit bullying based on sexual orientation, then it had no impact on the suicide attempt rates of LGB youth in that area.² Similar results were found when the relationship between anti–homophobic bullying policies and LGB suicide attempts was examined in the larger Youth Risk Behavior Surveillance System.³

State and local policies also influence other health outcomes among LGB youth. Hatzenbuehler et al. did another study that examined community-level determinants of tobacco use among LGB youth. Again using the data from the Oregon Healthy Teen Survey, they found that LGB youth living in communities that were more supportive of LGB youth (i.e., communities with a high proportion of same-sex couples living in the area, a high proportion of gay-straight alliances at schools, and LGB-specific antibullying policies) were less likely to smoke cigarettes, compared with LGB youth living in communities that were less supportive.⁴ A similar study in Canada by Konishi et al. found that schools with gay-straight alliances and anti–homophobic bullying policies were less likely to have LGB youth engaging in risky alcohol or illicit drug use.⁵

Why do these policies matter? A common theme among these policies is that they can either cause or alleviate stress for LGB youth. States that restrict same-sex marriages or schools that do not have any gay-straight alliances may signal to LGB youth that they are not valued or welcomed, or at the very worse, are despised. This creates a hostile and stressful environment for LGB youth, which raises the risk for mental health problems, such as depression and anxiety, which in turn, raises the risk for substance use and suicide.⁶ Conversely, the presence of a gay-straight alliance at school or a state that allows same-sex marriage may indicate to LGB youth that they are welcomed, if not just tolerated, and may alleviate this risk. Furthermore, antibullying policies seem to reduce the stress associated with bullying among LGB youth because it may serve as a deterrent to bullying based on sexual orientation. Although passing pro-LGB policies will not solve all the health problems among LGB youth, these policies certainly have an impact.

There might be trepidation among some pediatricians about being vocal on a politically charged policy proposal such as H.B. 780. However, suicide and substance use are major concerns for all physicians – especially pediatricians. Policy makers considering passing laws that can affect their LGB constituents should read these studies to see what kind of influence these proposals can have on the health and well-being of LGB youth. Moreover, health care providers should use their expertise, influence, and standing in their community to support policies that encourage protection for LGB youth and oppose policies that can harm LGB youth. These leaders are responsible for ensuring the health of the people they serve.
 

Dr. Montano is clinical instructor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC.

References

1. JAMA Pediatr. 2017. doi: 10.1001/jamapediatrics.2016.4529.

2. J Adolesc Health. 2013:S21-6. doi: 10.1016/j.jadohealth.2012.08.010.

3. Am J Public Health. 2014. doi: 10.2105/AJPH.2013.301508.

4. Arch Pediatr Adolesc Med. 2011. doi: 10.1001/archpediatrics.2011.64.

5. Prev Med. 2013. doi: 10.1016/j.ypmed.2013.06.031.

6. Psychol Bull. 2003. doi: 10.1037/0033-2909.129.5.674.

BOSTON – Fundamental questions remain over how best to use personalized medicine to predict and treat a variety of GI cancers, according to a panel of expert speakers at the 2017 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

“There are no rules presently, but we’re hoping to define some of the problems,” Abigail T. Berman, MD, MSCE, associate clinical director of the Penn Center for Precision Medicine in Philadelphia and associate professor of radiation oncology, told the audience. “To know how we’re going to pay for it, we need to define it.”

Emerging technologies: Worth the cost?

Among the growing number of novel predictive tools for clinical use is the liquid biopsy. Mechanical engineer Shannon Stott, PhD, assistant professor of medicine at Harvard Medical School, Boston, described how she applies her knowledge of microfluidics, optics, tissue engineering, and cryopreservation to clinical medicine and cell biology. She is the coinventor of the Herringbone Circulating Tumor Cell Chip, a liquid biopsy device that captures cancer cells circulating in the bloodstream of localized and metastatic cancer patients. By observing the biology of these extremely rare cells, she and her collaborators are helping identify novel pathways for metastasis.

Cost will drive innovation

Because precision medicine is high tech, it’s commonly assumed that it will prove too expensive to benefit the health of a population. Seen from a prevention perspective, however, that assumption is not necessarily true. Still, skepticism about the cost of precision medicine remains, Dr. Berman, citing an in-submission article she coauthored that compared standard to targeted therapy, said that for every $1,000 spent on targeted therapy, patients lived an average of 0.129 months vs. about 0.126 per $1,000 spent on standard therapies.

“Maybe we’re not saving payers money, but the field is not necessarily spending more and the patients are living longer,” she said. “This might be difficult to think about in front of the patient, but on the societal level, as reimbursements are decreasing, these are value-based therapies.”

Perhaps the biggest hurdle to establishing how to incorporate precision medicine into practice is data collection. Payers are starting to request multiple data streams to determine when a test or procedure is medically necessary or investigational. Other questions are what should be done when a test or procedure does not fit current evidentiary standards and at what point should it become exploratory. “The bottom line is that there is no consensus as to what payers should routinely reimburse,” she said.

In terms of managing the cost of targeted therapies, current debate seems to focus on a few potential solutions, according to Dr. Berman. One example is to develop a special entity that will pay for precision medicines up front, then the patient pays back the amount over time, with interest. Another possible solution is to spread the cost over large pools of individuals, rather than over large employee pools, similar to the way catastrophic insurance is currently structured. An additional critical approach is to conduct research using novel clinical trial designs, such as “basket” trials, where different tumors with the same mutation are given a similar targeted therapy. And yet another important approach is to standardize testing as much as possible to cut the cost of deviations in screening and treatment pathways.

Regardless of the solution, Dr. Berman said that at the heart of precision medicine should be ensuring that every patient is being treated in the most effective and value-based way.

–Heidi Splete contributed to this article.

BOSTON – Fundamental questions remain over how best to use personalized medicine to predict and treat a variety of GI cancers, according to a panel of expert speakers at the 2017 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

“There are no rules presently, but we’re hoping to define some of the problems,” Abigail T. Berman, MD, MSCE, associate clinical director of the Penn Center for Precision Medicine in Philadelphia and associate professor of radiation oncology, told the audience. “To know how we’re going to pay for it, we need to define it.”

Emerging technologies: Worth the cost?

Among the growing number of novel predictive tools for clinical use is the liquid biopsy. Mechanical engineer Shannon Stott, PhD, assistant professor of medicine at Harvard Medical School, Boston, described how she applies her knowledge of microfluidics, optics, tissue engineering, and cryopreservation to clinical medicine and cell biology. She is the coinventor of the Herringbone Circulating Tumor Cell Chip, a liquid biopsy device that captures cancer cells circulating in the bloodstream of localized and metastatic cancer patients. By observing the biology of these extremely rare cells, she and her collaborators are helping identify novel pathways for metastasis.

Cost will drive innovation

Because precision medicine is high tech, it’s commonly assumed that it will prove too expensive to benefit the health of a population. Seen from a prevention perspective, however, that assumption is not necessarily true. Still, skepticism about the cost of precision medicine remains, Dr. Berman, citing an in-submission article she coauthored that compared standard to targeted therapy, said that for every $1,000 spent on targeted therapy, patients lived an average of 0.129 months vs. about 0.126 per $1,000 spent on standard therapies.

“Maybe we’re not saving payers money, but the field is not necessarily spending more and the patients are living longer,” she said. “This might be difficult to think about in front of the patient, but on the societal level, as reimbursements are decreasing, these are value-based therapies.”

Perhaps the biggest hurdle to establishing how to incorporate precision medicine into practice is data collection. Payers are starting to request multiple data streams to determine when a test or procedure is medically necessary or investigational. Other questions are what should be done when a test or procedure does not fit current evidentiary standards and at what point should it become exploratory. “The bottom line is that there is no consensus as to what payers should routinely reimburse,” she said.

In terms of managing the cost of targeted therapies, current debate seems to focus on a few potential solutions, according to Dr. Berman. One example is to develop a special entity that will pay for precision medicines up front, then the patient pays back the amount over time, with interest. Another possible solution is to spread the cost over large pools of individuals, rather than over large employee pools, similar to the way catastrophic insurance is currently structured. An additional critical approach is to conduct research using novel clinical trial designs, such as “basket” trials, where different tumors with the same mutation are given a similar targeted therapy. And yet another important approach is to standardize testing as much as possible to cut the cost of deviations in screening and treatment pathways.

Regardless of the solution, Dr. Berman said that at the heart of precision medicine should be ensuring that every patient is being treated in the most effective and value-based way.

–Heidi Splete contributed to this article.

BOSTON – Fundamental questions remain over how best to use personalized medicine to predict and treat a variety of GI cancers, according to a panel of expert speakers at the 2017 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

“There are no rules presently, but we’re hoping to define some of the problems,” Abigail T. Berman, MD, MSCE, associate clinical director of the Penn Center for Precision Medicine in Philadelphia and associate professor of radiation oncology, told the audience. “To know how we’re going to pay for it, we need to define it.”

Emerging technologies: Worth the cost?

Among the growing number of novel predictive tools for clinical use is the liquid biopsy. Mechanical engineer Shannon Stott, PhD, assistant professor of medicine at Harvard Medical School, Boston, described how she applies her knowledge of microfluidics, optics, tissue engineering, and cryopreservation to clinical medicine and cell biology. She is the coinventor of the Herringbone Circulating Tumor Cell Chip, a liquid biopsy device that captures cancer cells circulating in the bloodstream of localized and metastatic cancer patients. By observing the biology of these extremely rare cells, she and her collaborators are helping identify novel pathways for metastasis.

Cost will drive innovation

Because precision medicine is high tech, it’s commonly assumed that it will prove too expensive to benefit the health of a population. Seen from a prevention perspective, however, that assumption is not necessarily true. Still, skepticism about the cost of precision medicine remains, Dr. Berman, citing an in-submission article she coauthored that compared standard to targeted therapy, said that for every $1,000 spent on targeted therapy, patients lived an average of 0.129 months vs. about 0.126 per $1,000 spent on standard therapies.

“Maybe we’re not saving payers money, but the field is not necessarily spending more and the patients are living longer,” she said. “This might be difficult to think about in front of the patient, but on the societal level, as reimbursements are decreasing, these are value-based therapies.”

Perhaps the biggest hurdle to establishing how to incorporate precision medicine into practice is data collection. Payers are starting to request multiple data streams to determine when a test or procedure is medically necessary or investigational. Other questions are what should be done when a test or procedure does not fit current evidentiary standards and at what point should it become exploratory. “The bottom line is that there is no consensus as to what payers should routinely reimburse,” she said.

In terms of managing the cost of targeted therapies, current debate seems to focus on a few potential solutions, according to Dr. Berman. One example is to develop a special entity that will pay for precision medicines up front, then the patient pays back the amount over time, with interest. Another possible solution is to spread the cost over large pools of individuals, rather than over large employee pools, similar to the way catastrophic insurance is currently structured. An additional critical approach is to conduct research using novel clinical trial designs, such as “basket” trials, where different tumors with the same mutation are given a similar targeted therapy. And yet another important approach is to standardize testing as much as possible to cut the cost of deviations in screening and treatment pathways.

Regardless of the solution, Dr. Berman said that at the heart of precision medicine should be ensuring that every patient is being treated in the most effective and value-based way.

–Heidi Splete contributed to this article.

STOWE, VT—Medication overuse headache is frequent, treatable, and preventable, according to an overview provided at the Headache Cooperative of New England’s 27th Annual Stowe Headache Symposium.

 The first step in treating medication overuse headache is to teach patients about the condition and how they can reduce their intake of acute medication. If patients still overuse medication, neurologists can prescribe a preventive therapy, such as topiramate or botulinum toxin. If preventive therapies fail, patients may require detoxification and integrated headache management, said Hans-Christoph Diener, MD, PhD, Senior Professor of Clinical Neurosciences and Director of the Headache Center at University Hospital Essen in Germany.

The diagnostic criteria for medication overuse headache include headache on 15 or more days per month, a pre-existing headache disorder, and regular overuse for more than three months of one or more acute or symptomatic headache drugs. The worldwide prevalence of medication overuse headache is about 1%, and about 10% of patients in headache centers have medication overuse headache.

Patients May Overuse Medication for Years

A meta-analysis of 29 studies with more than 2,600 patients found that medication overuse headache is more common in women than in men (3.5:1). About 65% of patients have a history of migraine, 27% have a history of tension-type headache, and 8% have a history of cluster headache. At diagnosis, patients’ average age is 40, average duration of primary headache is about 20 years, average duration of drug overuse is about 10 years, and average duration of medication overuse headache is about six years. “It is a slowly developing process,” Dr. Diener said. “Unfortunately, the patients present much too late.”

Risk factors include frequent headache, depression, anxiety, obesity, and other chronic pain conditions (eg, low back pain and fibromyalgia). Low socioeconomic status, being an immigrant, living alone, caffeine overuse, and opioid use also are associated with increased risk of medication overuse headache.

In an effort to treat patients with frequent episodic headache before they develop chronic migraine and medication overuse, Dr. Diener’s headache center evaluates high-risk patients who are referred by insurance companies. “If somebody has enough of these risk factors and frequent prescription of triptans, someone from the insurance company will call the patient and say, ‘Do you have problems with your headache?’” If so, the insurance company refers the patient. “In this way, we now get patients on the way to developing medication overuse, and we can treat them before they have full-blown medication overuse headache,” Dr. Diener said.

Overuse of triptans, ergots, barbiturates, and opioids may cause medication overuse headache, and a combination drug is more likely to cause medication overuse headache, compared with a drug with a single active ingredient. Limmroth et al conducted a prospective study of 98 patients with medication overuse headache to assess headache features associated with overuse of various drugs. With triptan overuse, migraine frequency increased in a majority of patients, and some patients developed a tension-type-like headache. With ergot overuse, patients tended to develop a tension-type-like daily headache. With analgesic overuse, the phenotype changed to a daily headache that resembled tension-type headache.

Start With Patient Education

When treating medication overuse headache, “simple advice is effective in a subgroup of patients,” Dr. Diener said. Grande et al taught 109 patients about medication overuse with the goal of reducing intake of acute medication. After 18 months, mean medication days per month significantly decreased from 22 at baseline to six. Education “worked in the majority of these patients,” Dr. Diener said.

Rossi et al conducted a prospective randomized trial in Italy that included 120 patients with medication overuse headache. The researchers randomized patients to advice, a structured outpatient program, or a one-week inpatient program. “There was basically no difference” between the three groups at four and eight weeks, Dr. Diener said. All three groups experienced a reduction in medication days per month of between 70% and 80%.

Do Preventive Therapies Work?

Neurologists had thought that medication overuse might render preventive medication ineffective, but studies have found that topiramate and onabotulinum toxinA are effective preventive agents in this population. The trials excluded patients who had overused barbiturates or opioids, however. In such cases, “it is not only overuse, it is addiction,” Dr. Diener said. “That is a totally different disease.”

Dr. Diener and colleagues conducted a randomized trial of topiramate in patients with chronic migraine. A majority of the patients overused triptans (ie, they took triptans on at least 10 days per four weeks). Patients had about 16 migraine days per month.

Compared with baseline, patients who received placebo had virtually no change in headache days per month, whereas patients who received topiramate had about five fewer headache days per month at 16 weeks. Two-thirds of patients in the active treatment group no longer overused medication at the end of the study. A parallel study in the United States had similar results. “We should offer this [treatment] to patients prior to drug withdrawal,” Dr. Diener said. “If patients refuse or cannot tolerate the drug,” then neurologists may consider other options, including botulinum toxin.

OnabotulinumtoxinA was evaluated in two trials. About 65% of patients overused medication in the active treatment and placebo groups of each trial, and treatment significantly reduced headache days in patients who did and did not overuse medication. In addition, compared with patients who received placebo, a greater proportion of patients who received onabotulinumtoxinA no longer overused medication for three and six consecutive months. Patients can choose between topiramate tablets and onabotulinumtoxinA injections as preventive therapy, Dr. Diener said.

Detoxification

If preventive medication fails to help patients, the next step is detoxification. Dr. Diener has patients stop acute medications cold turkey and initiates preventive therapy at that time. Patients at Dr. Diener’s center normally undergo detoxification on an outpatient basis.

Chiang et al assessed the evidence for withdrawal, withdrawal with preventive medications, and preventive medications alone. Withdrawal and withdrawal with preventive medications were found to be possibly effective, while the use of preventive medications alone was found to be likely effective. Withdrawal alone has a high failure rate and worsens symptoms in some patients. Withdrawal with preventive medication produced encouraging results in some studies, but the studies lacked control groups.

Studies suggest that the relapse rate for medication overuse headache is about 10% per year, Dr. Diener said.

One Center’s Experience

At Essen Headache Center, researchers prospectively studied 150 patients who had a diagnosis of migraine and medication overuse headache. A third achieved successful treatment with counseling and education. Another third benefited from topiramate or botulinum toxin. And the remaining third required detoxification. The majority of patients requiring detoxification had comorbidities (eg, chronic low back pain or depression). These patients require integrated headache care, including preventive therapy, exercise and physiotherapy, behavioral therapy (eg, stress management and relaxation), and education.

“The most important part is education,” Dr. Diener said. Headache center staff members tell patients that they will leave the center knowing more about their condition than their general practitioner does. “This is the goal that we want to achieve,” he said.

—Jake Remaly

Suggested Reading

Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016;36(4):371-386.

Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804-814.

Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29(10):1021-1027.

Diener HC, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.

Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129-137.

Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011-1014.

Pijpers JA, Louter MA, de Bruin ME, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122-130.

Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia. 2006;26(9):1097-1105.

STOWE, VT—Medication overuse headache is frequent, treatable, and preventable, according to an overview provided at the Headache Cooperative of New England’s 27th Annual Stowe Headache Symposium.

 The first step in treating medication overuse headache is to teach patients about the condition and how they can reduce their intake of acute medication. If patients still overuse medication, neurologists can prescribe a preventive therapy, such as topiramate or botulinum toxin. If preventive therapies fail, patients may require detoxification and integrated headache management, said Hans-Christoph Diener, MD, PhD, Senior Professor of Clinical Neurosciences and Director of the Headache Center at University Hospital Essen in Germany.

The diagnostic criteria for medication overuse headache include headache on 15 or more days per month, a pre-existing headache disorder, and regular overuse for more than three months of one or more acute or symptomatic headache drugs. The worldwide prevalence of medication overuse headache is about 1%, and about 10% of patients in headache centers have medication overuse headache.

Patients May Overuse Medication for Years

A meta-analysis of 29 studies with more than 2,600 patients found that medication overuse headache is more common in women than in men (3.5:1). About 65% of patients have a history of migraine, 27% have a history of tension-type headache, and 8% have a history of cluster headache. At diagnosis, patients’ average age is 40, average duration of primary headache is about 20 years, average duration of drug overuse is about 10 years, and average duration of medication overuse headache is about six years. “It is a slowly developing process,” Dr. Diener said. “Unfortunately, the patients present much too late.”

Risk factors include frequent headache, depression, anxiety, obesity, and other chronic pain conditions (eg, low back pain and fibromyalgia). Low socioeconomic status, being an immigrant, living alone, caffeine overuse, and opioid use also are associated with increased risk of medication overuse headache.

In an effort to treat patients with frequent episodic headache before they develop chronic migraine and medication overuse, Dr. Diener’s headache center evaluates high-risk patients who are referred by insurance companies. “If somebody has enough of these risk factors and frequent prescription of triptans, someone from the insurance company will call the patient and say, ‘Do you have problems with your headache?’” If so, the insurance company refers the patient. “In this way, we now get patients on the way to developing medication overuse, and we can treat them before they have full-blown medication overuse headache,” Dr. Diener said.

Overuse of triptans, ergots, barbiturates, and opioids may cause medication overuse headache, and a combination drug is more likely to cause medication overuse headache, compared with a drug with a single active ingredient. Limmroth et al conducted a prospective study of 98 patients with medication overuse headache to assess headache features associated with overuse of various drugs. With triptan overuse, migraine frequency increased in a majority of patients, and some patients developed a tension-type-like headache. With ergot overuse, patients tended to develop a tension-type-like daily headache. With analgesic overuse, the phenotype changed to a daily headache that resembled tension-type headache.

Start With Patient Education

When treating medication overuse headache, “simple advice is effective in a subgroup of patients,” Dr. Diener said. Grande et al taught 109 patients about medication overuse with the goal of reducing intake of acute medication. After 18 months, mean medication days per month significantly decreased from 22 at baseline to six. Education “worked in the majority of these patients,” Dr. Diener said.

Rossi et al conducted a prospective randomized trial in Italy that included 120 patients with medication overuse headache. The researchers randomized patients to advice, a structured outpatient program, or a one-week inpatient program. “There was basically no difference” between the three groups at four and eight weeks, Dr. Diener said. All three groups experienced a reduction in medication days per month of between 70% and 80%.

Do Preventive Therapies Work?

Neurologists had thought that medication overuse might render preventive medication ineffective, but studies have found that topiramate and onabotulinum toxinA are effective preventive agents in this population. The trials excluded patients who had overused barbiturates or opioids, however. In such cases, “it is not only overuse, it is addiction,” Dr. Diener said. “That is a totally different disease.”

Dr. Diener and colleagues conducted a randomized trial of topiramate in patients with chronic migraine. A majority of the patients overused triptans (ie, they took triptans on at least 10 days per four weeks). Patients had about 16 migraine days per month.

Compared with baseline, patients who received placebo had virtually no change in headache days per month, whereas patients who received topiramate had about five fewer headache days per month at 16 weeks. Two-thirds of patients in the active treatment group no longer overused medication at the end of the study. A parallel study in the United States had similar results. “We should offer this [treatment] to patients prior to drug withdrawal,” Dr. Diener said. “If patients refuse or cannot tolerate the drug,” then neurologists may consider other options, including botulinum toxin.

OnabotulinumtoxinA was evaluated in two trials. About 65% of patients overused medication in the active treatment and placebo groups of each trial, and treatment significantly reduced headache days in patients who did and did not overuse medication. In addition, compared with patients who received placebo, a greater proportion of patients who received onabotulinumtoxinA no longer overused medication for three and six consecutive months. Patients can choose between topiramate tablets and onabotulinumtoxinA injections as preventive therapy, Dr. Diener said.

Detoxification

If preventive medication fails to help patients, the next step is detoxification. Dr. Diener has patients stop acute medications cold turkey and initiates preventive therapy at that time. Patients at Dr. Diener’s center normally undergo detoxification on an outpatient basis.

Chiang et al assessed the evidence for withdrawal, withdrawal with preventive medications, and preventive medications alone. Withdrawal and withdrawal with preventive medications were found to be possibly effective, while the use of preventive medications alone was found to be likely effective. Withdrawal alone has a high failure rate and worsens symptoms in some patients. Withdrawal with preventive medication produced encouraging results in some studies, but the studies lacked control groups.

Studies suggest that the relapse rate for medication overuse headache is about 10% per year, Dr. Diener said.

One Center’s Experience

At Essen Headache Center, researchers prospectively studied 150 patients who had a diagnosis of migraine and medication overuse headache. A third achieved successful treatment with counseling and education. Another third benefited from topiramate or botulinum toxin. And the remaining third required detoxification. The majority of patients requiring detoxification had comorbidities (eg, chronic low back pain or depression). These patients require integrated headache care, including preventive therapy, exercise and physiotherapy, behavioral therapy (eg, stress management and relaxation), and education.

“The most important part is education,” Dr. Diener said. Headache center staff members tell patients that they will leave the center knowing more about their condition than their general practitioner does. “This is the goal that we want to achieve,” he said.

—Jake Remaly

Suggested Reading

Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016;36(4):371-386.

Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804-814.

Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29(10):1021-1027.

Diener HC, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.

Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129-137.

Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011-1014.

Pijpers JA, Louter MA, de Bruin ME, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122-130.

Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia. 2006;26(9):1097-1105.

STOWE, VT—Medication overuse headache is frequent, treatable, and preventable, according to an overview provided at the Headache Cooperative of New England’s 27th Annual Stowe Headache Symposium.

 The first step in treating medication overuse headache is to teach patients about the condition and how they can reduce their intake of acute medication. If patients still overuse medication, neurologists can prescribe a preventive therapy, such as topiramate or botulinum toxin. If preventive therapies fail, patients may require detoxification and integrated headache management, said Hans-Christoph Diener, MD, PhD, Senior Professor of Clinical Neurosciences and Director of the Headache Center at University Hospital Essen in Germany.

The diagnostic criteria for medication overuse headache include headache on 15 or more days per month, a pre-existing headache disorder, and regular overuse for more than three months of one or more acute or symptomatic headache drugs. The worldwide prevalence of medication overuse headache is about 1%, and about 10% of patients in headache centers have medication overuse headache.

Patients May Overuse Medication for Years

A meta-analysis of 29 studies with more than 2,600 patients found that medication overuse headache is more common in women than in men (3.5:1). About 65% of patients have a history of migraine, 27% have a history of tension-type headache, and 8% have a history of cluster headache. At diagnosis, patients’ average age is 40, average duration of primary headache is about 20 years, average duration of drug overuse is about 10 years, and average duration of medication overuse headache is about six years. “It is a slowly developing process,” Dr. Diener said. “Unfortunately, the patients present much too late.”

Risk factors include frequent headache, depression, anxiety, obesity, and other chronic pain conditions (eg, low back pain and fibromyalgia). Low socioeconomic status, being an immigrant, living alone, caffeine overuse, and opioid use also are associated with increased risk of medication overuse headache.

In an effort to treat patients with frequent episodic headache before they develop chronic migraine and medication overuse, Dr. Diener’s headache center evaluates high-risk patients who are referred by insurance companies. “If somebody has enough of these risk factors and frequent prescription of triptans, someone from the insurance company will call the patient and say, ‘Do you have problems with your headache?’” If so, the insurance company refers the patient. “In this way, we now get patients on the way to developing medication overuse, and we can treat them before they have full-blown medication overuse headache,” Dr. Diener said.

Overuse of triptans, ergots, barbiturates, and opioids may cause medication overuse headache, and a combination drug is more likely to cause medication overuse headache, compared with a drug with a single active ingredient. Limmroth et al conducted a prospective study of 98 patients with medication overuse headache to assess headache features associated with overuse of various drugs. With triptan overuse, migraine frequency increased in a majority of patients, and some patients developed a tension-type-like headache. With ergot overuse, patients tended to develop a tension-type-like daily headache. With analgesic overuse, the phenotype changed to a daily headache that resembled tension-type headache.

Start With Patient Education

When treating medication overuse headache, “simple advice is effective in a subgroup of patients,” Dr. Diener said. Grande et al taught 109 patients about medication overuse with the goal of reducing intake of acute medication. After 18 months, mean medication days per month significantly decreased from 22 at baseline to six. Education “worked in the majority of these patients,” Dr. Diener said.

Rossi et al conducted a prospective randomized trial in Italy that included 120 patients with medication overuse headache. The researchers randomized patients to advice, a structured outpatient program, or a one-week inpatient program. “There was basically no difference” between the three groups at four and eight weeks, Dr. Diener said. All three groups experienced a reduction in medication days per month of between 70% and 80%.

Do Preventive Therapies Work?

Neurologists had thought that medication overuse might render preventive medication ineffective, but studies have found that topiramate and onabotulinum toxinA are effective preventive agents in this population. The trials excluded patients who had overused barbiturates or opioids, however. In such cases, “it is not only overuse, it is addiction,” Dr. Diener said. “That is a totally different disease.”

Dr. Diener and colleagues conducted a randomized trial of topiramate in patients with chronic migraine. A majority of the patients overused triptans (ie, they took triptans on at least 10 days per four weeks). Patients had about 16 migraine days per month.

Compared with baseline, patients who received placebo had virtually no change in headache days per month, whereas patients who received topiramate had about five fewer headache days per month at 16 weeks. Two-thirds of patients in the active treatment group no longer overused medication at the end of the study. A parallel study in the United States had similar results. “We should offer this [treatment] to patients prior to drug withdrawal,” Dr. Diener said. “If patients refuse or cannot tolerate the drug,” then neurologists may consider other options, including botulinum toxin.

OnabotulinumtoxinA was evaluated in two trials. About 65% of patients overused medication in the active treatment and placebo groups of each trial, and treatment significantly reduced headache days in patients who did and did not overuse medication. In addition, compared with patients who received placebo, a greater proportion of patients who received onabotulinumtoxinA no longer overused medication for three and six consecutive months. Patients can choose between topiramate tablets and onabotulinumtoxinA injections as preventive therapy, Dr. Diener said.

Detoxification

If preventive medication fails to help patients, the next step is detoxification. Dr. Diener has patients stop acute medications cold turkey and initiates preventive therapy at that time. Patients at Dr. Diener’s center normally undergo detoxification on an outpatient basis.

Chiang et al assessed the evidence for withdrawal, withdrawal with preventive medications, and preventive medications alone. Withdrawal and withdrawal with preventive medications were found to be possibly effective, while the use of preventive medications alone was found to be likely effective. Withdrawal alone has a high failure rate and worsens symptoms in some patients. Withdrawal with preventive medication produced encouraging results in some studies, but the studies lacked control groups.

Studies suggest that the relapse rate for medication overuse headache is about 10% per year, Dr. Diener said.

One Center’s Experience

At Essen Headache Center, researchers prospectively studied 150 patients who had a diagnosis of migraine and medication overuse headache. A third achieved successful treatment with counseling and education. Another third benefited from topiramate or botulinum toxin. And the remaining third required detoxification. The majority of patients requiring detoxification had comorbidities (eg, chronic low back pain or depression). These patients require integrated headache care, including preventive therapy, exercise and physiotherapy, behavioral therapy (eg, stress management and relaxation), and education.

“The most important part is education,” Dr. Diener said. Headache center staff members tell patients that they will leave the center knowing more about their condition than their general practitioner does. “This is the goal that we want to achieve,” he said.

—Jake Remaly

Suggested Reading

Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016;36(4):371-386.

Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30(7):804-814.

Diener HC, Dodick DW, Goadsby PJ, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29(10):1021-1027.

Diener HC, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.

Grande RB, Aaseth K, Benth JŠ, et al. Reduction in medication-overuse headache after short information. The Akershus study of chronic headache. Eur J Neurol. 2011;18(1):129-137.

Limmroth V, Katsarava Z, Fritsche G, et al. Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59(7):1011-1014.

Pijpers JA, Louter MA, de Bruin ME, et al. Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure? Cephalalgia. 2016;36(2):122-130.

Rossi P, Di Lorenzo C, Faroni J, et al. Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs. Cephalalgia. 2006;26(9):1097-1105.

Patients who undergo follow-up colonoscopy 10 months or more after a positive fecal immunochemical test are at higher risk for colorectal cancer, and for having more advanced disease at diagnosis, than are those who undergo immediate (within 30 days) follow-up colonoscopy, according to a new report.

Clinical practice guidelines recommend follow-up colonoscopy after a positive fecal immunochemical test (FIT) result but differ about how quickly the procedure should be done, chiefly because there is little evidence on which to base any recommendation regarding timing, reported Douglas A. Corley, MD, PhD, of Kaiser Permanente Northern California, Oakland, and his associates. The study results were published in JAMA.

[email protected]

Patients who undergo follow-up colonoscopy 10 months or more after a positive fecal immunochemical test are at higher risk for colorectal cancer, and for having more advanced disease at diagnosis, than are those who undergo immediate (within 30 days) follow-up colonoscopy, according to a new report.

Clinical practice guidelines recommend follow-up colonoscopy after a positive fecal immunochemical test (FIT) result but differ about how quickly the procedure should be done, chiefly because there is little evidence on which to base any recommendation regarding timing, reported Douglas A. Corley, MD, PhD, of Kaiser Permanente Northern California, Oakland, and his associates. The study results were published in JAMA.

[email protected]

Patients who undergo follow-up colonoscopy 10 months or more after a positive fecal immunochemical test are at higher risk for colorectal cancer, and for having more advanced disease at diagnosis, than are those who undergo immediate (within 30 days) follow-up colonoscopy, according to a new report.

Clinical practice guidelines recommend follow-up colonoscopy after a positive fecal immunochemical test (FIT) result but differ about how quickly the procedure should be done, chiefly because there is little evidence on which to base any recommendation regarding timing, reported Douglas A. Corley, MD, PhD, of Kaiser Permanente Northern California, Oakland, and his associates. The study results were published in JAMA.

[email protected]

HOUSTON – An ambulatory approach to laparoscopic sleeve gastrectomy is a safe and viable option to improve patient satisfaction and soften the economic blow of these procedures on patients, based on a large series at one surgery center in Cincinnati.

“With proper patient selection, utilization of enhanced recovery pathways with an overall low readmission rate and the complication profile point to the feasibility of laparoscopic sleeve gastrectomy [LSG] as a safe outpatient procedure,” said Sepehr Lalezari, MD, now a surgical fellow at Johns Hopkins University, Baltimore.

[email protected]

HOUSTON – An ambulatory approach to laparoscopic sleeve gastrectomy is a safe and viable option to improve patient satisfaction and soften the economic blow of these procedures on patients, based on a large series at one surgery center in Cincinnati.

“With proper patient selection, utilization of enhanced recovery pathways with an overall low readmission rate and the complication profile point to the feasibility of laparoscopic sleeve gastrectomy [LSG] as a safe outpatient procedure,” said Sepehr Lalezari, MD, now a surgical fellow at Johns Hopkins University, Baltimore.

[email protected]

HOUSTON – An ambulatory approach to laparoscopic sleeve gastrectomy is a safe and viable option to improve patient satisfaction and soften the economic blow of these procedures on patients, based on a large series at one surgery center in Cincinnati.

“With proper patient selection, utilization of enhanced recovery pathways with an overall low readmission rate and the complication profile point to the feasibility of laparoscopic sleeve gastrectomy [LSG] as a safe outpatient procedure,” said Sepehr Lalezari, MD, now a surgical fellow at Johns Hopkins University, Baltimore.

[email protected]

BOSTON – Texas neurologist Louise McCullough, MD, PhD, is determined to help women live longer by urging neurologists to focus on the unique risks and needs involved.

Dr. McCullough, chief of neurology at Memorial Hermann Hospital in Houston, told a plenary audience at the annual meeting of the American Academy of Neurology that both biological and social factors contribute to conditions, such as atrial fibrillation, that are more dangerous in females than in males.

For example, women are less likely than men to be taking blood thinners, she said, possibly because doctors assume they’re frail even when they’ll confirm – if only someone asks – that they haven’t fallen.

At the same time, she said, women with atrial fibrillation are twice as likely as their male counterparts to suffer a stroke. “You need to screen older women for a-fib and have a much lower threshold for treatment.”

Isolation can be another contributing factor to the stroke gender gap, she said. “Women are often living alone – they’ve outlived their spouses; they don’t live near their children; they may not have access to rapid care.”

These factors, she said, may even contribute to the smaller presence of women in clinical trials.

Dr. McCullough discussed these issues and more in a video interview at the meeting.

BOSTON – Texas neurologist Louise McCullough, MD, PhD, is determined to help women live longer by urging neurologists to focus on the unique risks and needs involved.

Dr. McCullough, chief of neurology at Memorial Hermann Hospital in Houston, told a plenary audience at the annual meeting of the American Academy of Neurology that both biological and social factors contribute to conditions, such as atrial fibrillation, that are more dangerous in females than in males.

For example, women are less likely than men to be taking blood thinners, she said, possibly because doctors assume they’re frail even when they’ll confirm – if only someone asks – that they haven’t fallen.

At the same time, she said, women with atrial fibrillation are twice as likely as their male counterparts to suffer a stroke. “You need to screen older women for a-fib and have a much lower threshold for treatment.”

Isolation can be another contributing factor to the stroke gender gap, she said. “Women are often living alone – they’ve outlived their spouses; they don’t live near their children; they may not have access to rapid care.”

These factors, she said, may even contribute to the smaller presence of women in clinical trials.

Dr. McCullough discussed these issues and more in a video interview at the meeting.

BOSTON – Texas neurologist Louise McCullough, MD, PhD, is determined to help women live longer by urging neurologists to focus on the unique risks and needs involved.

Dr. McCullough, chief of neurology at Memorial Hermann Hospital in Houston, told a plenary audience at the annual meeting of the American Academy of Neurology that both biological and social factors contribute to conditions, such as atrial fibrillation, that are more dangerous in females than in males.

For example, women are less likely than men to be taking blood thinners, she said, possibly because doctors assume they’re frail even when they’ll confirm – if only someone asks – that they haven’t fallen.

At the same time, she said, women with atrial fibrillation are twice as likely as their male counterparts to suffer a stroke. “You need to screen older women for a-fib and have a much lower threshold for treatment.”

Isolation can be another contributing factor to the stroke gender gap, she said. “Women are often living alone – they’ve outlived their spouses; they don’t live near their children; they may not have access to rapid care.”

These factors, she said, may even contribute to the smaller presence of women in clinical trials.

Dr. McCullough discussed these issues and more in a video interview at the meeting.

Dating during residency is a job unto itself – one that I didn’t expect to balance alongside my long and frequently odd hours of work. To make matters worse, I happen to be in a field where the examination is almost entirely through conversation, involving probing questions, where maintaining calm and strength is important in the face of patient stories that often tear at my heart. Then, on a date (first or otherwise) I spend more time listening to another person’s stories while trying hard not to interpret the information through the perspective of my profession. To orient my older readers, I primarily date using the Internet and dating applications. There, my profile names me as “Resident.” This title is unassuming and unintimidating. Resident of what, potential suitors wonder, while examining carefully curated pictures of travel to exotic places and of me smiling happily with friends. I swipe right and left, matching with people, chatting digitally at first, and, if there is mutual interest, arranging to meet in person.

I get a different reaction every time I tell a date I’m a psychiatrist. It seems each man has his own expectations of what it means to date a psychiatrist. This column is a shout-out to all the physicians, and especially psychiatrists, who have been single while practicing, required to pretend our work is just like everyone else’s. Because the truth is, our work is different. How can one really describe the goings-on at a psychiatric hospital to a potential partner? Or deal with fatigue that accompanies listening to emotional suffering while at work and then needing the energy to commiserate with the person across the table?

Dr. Posada is a second-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.

Dating during residency is a job unto itself – one that I didn’t expect to balance alongside my long and frequently odd hours of work. To make matters worse, I happen to be in a field where the examination is almost entirely through conversation, involving probing questions, where maintaining calm and strength is important in the face of patient stories that often tear at my heart. Then, on a date (first or otherwise) I spend more time listening to another person’s stories while trying hard not to interpret the information through the perspective of my profession. To orient my older readers, I primarily date using the Internet and dating applications. There, my profile names me as “Resident.” This title is unassuming and unintimidating. Resident of what, potential suitors wonder, while examining carefully curated pictures of travel to exotic places and of me smiling happily with friends. I swipe right and left, matching with people, chatting digitally at first, and, if there is mutual interest, arranging to meet in person.

I get a different reaction every time I tell a date I’m a psychiatrist. It seems each man has his own expectations of what it means to date a psychiatrist. This column is a shout-out to all the physicians, and especially psychiatrists, who have been single while practicing, required to pretend our work is just like everyone else’s. Because the truth is, our work is different. How can one really describe the goings-on at a psychiatric hospital to a potential partner? Or deal with fatigue that accompanies listening to emotional suffering while at work and then needing the energy to commiserate with the person across the table?

Dr. Posada is a second-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.

Dating during residency is a job unto itself – one that I didn’t expect to balance alongside my long and frequently odd hours of work. To make matters worse, I happen to be in a field where the examination is almost entirely through conversation, involving probing questions, where maintaining calm and strength is important in the face of patient stories that often tear at my heart. Then, on a date (first or otherwise) I spend more time listening to another person’s stories while trying hard not to interpret the information through the perspective of my profession. To orient my older readers, I primarily date using the Internet and dating applications. There, my profile names me as “Resident.” This title is unassuming and unintimidating. Resident of what, potential suitors wonder, while examining carefully curated pictures of travel to exotic places and of me smiling happily with friends. I swipe right and left, matching with people, chatting digitally at first, and, if there is mutual interest, arranging to meet in person.

I get a different reaction every time I tell a date I’m a psychiatrist. It seems each man has his own expectations of what it means to date a psychiatrist. This column is a shout-out to all the physicians, and especially psychiatrists, who have been single while practicing, required to pretend our work is just like everyone else’s. Because the truth is, our work is different. How can one really describe the goings-on at a psychiatric hospital to a potential partner? Or deal with fatigue that accompanies listening to emotional suffering while at work and then needing the energy to commiserate with the person across the table?

Dr. Posada is a second-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, health disparities, and psychosomatic medicine.