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Study Explores Link Between GERD and Poor Sleep Quality
The proportion of adults with GERD has increased, and GERD increases the likelihood of dissatisfaction with sleep.
ATLANTA—Chronic gastroesophageal reflux disease (GERD) is associated with various sleep disorders that might complicate the response to GERD treatment, according to an ongoing longitudinal analysis presented at the 143rd Annual Meeting of the American Neurological Association.
“We have little longitudinal information on GERD in the general population; the last published article on GERD incidence was 20 years ago,” said lead study author Maurice M. Ohayon, MD, DSc, PhD, Director of the Stanford Sleep Epidemiology Research Center in California. “As a sleep specialist, I am always interested to see how a specific medical condition may affect the sleep quality of the individuals with that condition. How we live our day has an impact on our night; it works together.”
Proton-Pump Inhibitors Are Common Treatments
To examine the long-term effects of GERD on sleep disturbances, Dr. Ohayon and his colleagues used US Census data to identify a random sample of adults in Arizona, California, Colorado, Idaho, New York, Oregon, Pennsylvania, and Texas. The researchers conducted two waves of phone interviews with the subjects three years apart, beginning in 2004. They limited their analysis to 10,930 subjects with a mean age of 43 who participated in both interviews.
Between Wave 1 and Wave 2 of phone interviews, the proportion of adults who reported having GERD rose from 10.6% to 12.4%. The prevalence of new GERD cases was 8.5% per year, while the incidence was 3.2% per year. Chronic GERD, defined as GERD present during both interview periods, was observed in 3.9% of the sample.
The researchers found that 77.3% of subjects with GERD were taking a treatment, mostly proton-pump inhibitors, to alleviate their symptoms. Those with chronic GERD were more likely to report being dissatisfied with their sleep during Wave 2 of the study, compared with Wave 1 (24.2% vs 13.5%). In addition, compared with their counterparts without GERD, those with chronic GERD were more likely to wake up at night (33.9% vs 28.3%) and to have nonrestorative sleep (15.6% vs 10.5%).
“Discomfort related to GERD may happen while you are sleeping,” said Dr. Ohayon. “It may wake you up and, if not, it may make you feel unrested when you wake up. We observed both of these symptoms in our GERD participants. Insomnia disorders were also rampant in the chronic GERD group (24.5%, compared with 14.4% in non-GERD participants). An insomnia disorder is more than just having difficulty falling asleep or waking up at night, it means that your daytime functioning is affected by the poor quality of your night.”
GERD May Promote Weight Gain
Other findings from the study were “rather alarming,” said Dr. Ohayon. For example, individuals with GERD, especially those with the chronic form, weighed much more than those with no GERD did. “Over a three-year period, the chronic GERD individuals gained one point in the BMI, which for a six-foot tall man translates into a weight gain of 30 pounds,” he said. “Of course, with that follows high blood pressure, high cholesterol, diabetes, chronic pain, and heart disease.”
He concluded that GERD has its main manifestations when affected individuals are sleeping on their backs. “The impact of GERD on the quality of sleep is major,” he said. “Sleepiness and fatigue during the day are the consequences impacting work, family, and quality of life.”
Dr. Ohayon acknowledged certain limitations of the study, including the fact that the diagnosis of GERD was based on self-report. The study was supported by an unrestricted grant from Takeda.
—Doug Brunk
The proportion of adults with GERD has increased, and GERD increases the likelihood of dissatisfaction with sleep.
The proportion of adults with GERD has increased, and GERD increases the likelihood of dissatisfaction with sleep.
ATLANTA—Chronic gastroesophageal reflux disease (GERD) is associated with various sleep disorders that might complicate the response to GERD treatment, according to an ongoing longitudinal analysis presented at the 143rd Annual Meeting of the American Neurological Association.
“We have little longitudinal information on GERD in the general population; the last published article on GERD incidence was 20 years ago,” said lead study author Maurice M. Ohayon, MD, DSc, PhD, Director of the Stanford Sleep Epidemiology Research Center in California. “As a sleep specialist, I am always interested to see how a specific medical condition may affect the sleep quality of the individuals with that condition. How we live our day has an impact on our night; it works together.”
Proton-Pump Inhibitors Are Common Treatments
To examine the long-term effects of GERD on sleep disturbances, Dr. Ohayon and his colleagues used US Census data to identify a random sample of adults in Arizona, California, Colorado, Idaho, New York, Oregon, Pennsylvania, and Texas. The researchers conducted two waves of phone interviews with the subjects three years apart, beginning in 2004. They limited their analysis to 10,930 subjects with a mean age of 43 who participated in both interviews.
Between Wave 1 and Wave 2 of phone interviews, the proportion of adults who reported having GERD rose from 10.6% to 12.4%. The prevalence of new GERD cases was 8.5% per year, while the incidence was 3.2% per year. Chronic GERD, defined as GERD present during both interview periods, was observed in 3.9% of the sample.
The researchers found that 77.3% of subjects with GERD were taking a treatment, mostly proton-pump inhibitors, to alleviate their symptoms. Those with chronic GERD were more likely to report being dissatisfied with their sleep during Wave 2 of the study, compared with Wave 1 (24.2% vs 13.5%). In addition, compared with their counterparts without GERD, those with chronic GERD were more likely to wake up at night (33.9% vs 28.3%) and to have nonrestorative sleep (15.6% vs 10.5%).
“Discomfort related to GERD may happen while you are sleeping,” said Dr. Ohayon. “It may wake you up and, if not, it may make you feel unrested when you wake up. We observed both of these symptoms in our GERD participants. Insomnia disorders were also rampant in the chronic GERD group (24.5%, compared with 14.4% in non-GERD participants). An insomnia disorder is more than just having difficulty falling asleep or waking up at night, it means that your daytime functioning is affected by the poor quality of your night.”
GERD May Promote Weight Gain
Other findings from the study were “rather alarming,” said Dr. Ohayon. For example, individuals with GERD, especially those with the chronic form, weighed much more than those with no GERD did. “Over a three-year period, the chronic GERD individuals gained one point in the BMI, which for a six-foot tall man translates into a weight gain of 30 pounds,” he said. “Of course, with that follows high blood pressure, high cholesterol, diabetes, chronic pain, and heart disease.”
He concluded that GERD has its main manifestations when affected individuals are sleeping on their backs. “The impact of GERD on the quality of sleep is major,” he said. “Sleepiness and fatigue during the day are the consequences impacting work, family, and quality of life.”
Dr. Ohayon acknowledged certain limitations of the study, including the fact that the diagnosis of GERD was based on self-report. The study was supported by an unrestricted grant from Takeda.
—Doug Brunk
ATLANTA—Chronic gastroesophageal reflux disease (GERD) is associated with various sleep disorders that might complicate the response to GERD treatment, according to an ongoing longitudinal analysis presented at the 143rd Annual Meeting of the American Neurological Association.
“We have little longitudinal information on GERD in the general population; the last published article on GERD incidence was 20 years ago,” said lead study author Maurice M. Ohayon, MD, DSc, PhD, Director of the Stanford Sleep Epidemiology Research Center in California. “As a sleep specialist, I am always interested to see how a specific medical condition may affect the sleep quality of the individuals with that condition. How we live our day has an impact on our night; it works together.”
Proton-Pump Inhibitors Are Common Treatments
To examine the long-term effects of GERD on sleep disturbances, Dr. Ohayon and his colleagues used US Census data to identify a random sample of adults in Arizona, California, Colorado, Idaho, New York, Oregon, Pennsylvania, and Texas. The researchers conducted two waves of phone interviews with the subjects three years apart, beginning in 2004. They limited their analysis to 10,930 subjects with a mean age of 43 who participated in both interviews.
Between Wave 1 and Wave 2 of phone interviews, the proportion of adults who reported having GERD rose from 10.6% to 12.4%. The prevalence of new GERD cases was 8.5% per year, while the incidence was 3.2% per year. Chronic GERD, defined as GERD present during both interview periods, was observed in 3.9% of the sample.
The researchers found that 77.3% of subjects with GERD were taking a treatment, mostly proton-pump inhibitors, to alleviate their symptoms. Those with chronic GERD were more likely to report being dissatisfied with their sleep during Wave 2 of the study, compared with Wave 1 (24.2% vs 13.5%). In addition, compared with their counterparts without GERD, those with chronic GERD were more likely to wake up at night (33.9% vs 28.3%) and to have nonrestorative sleep (15.6% vs 10.5%).
“Discomfort related to GERD may happen while you are sleeping,” said Dr. Ohayon. “It may wake you up and, if not, it may make you feel unrested when you wake up. We observed both of these symptoms in our GERD participants. Insomnia disorders were also rampant in the chronic GERD group (24.5%, compared with 14.4% in non-GERD participants). An insomnia disorder is more than just having difficulty falling asleep or waking up at night, it means that your daytime functioning is affected by the poor quality of your night.”
GERD May Promote Weight Gain
Other findings from the study were “rather alarming,” said Dr. Ohayon. For example, individuals with GERD, especially those with the chronic form, weighed much more than those with no GERD did. “Over a three-year period, the chronic GERD individuals gained one point in the BMI, which for a six-foot tall man translates into a weight gain of 30 pounds,” he said. “Of course, with that follows high blood pressure, high cholesterol, diabetes, chronic pain, and heart disease.”
He concluded that GERD has its main manifestations when affected individuals are sleeping on their backs. “The impact of GERD on the quality of sleep is major,” he said. “Sleepiness and fatigue during the day are the consequences impacting work, family, and quality of life.”
Dr. Ohayon acknowledged certain limitations of the study, including the fact that the diagnosis of GERD was based on self-report. The study was supported by an unrestricted grant from Takeda.
—Doug Brunk
To Escalate or Not to Escalate MS Therapy After Relapses?
Switching from a moderately effective treatment to a highly effective treatment can improve outcomes.
BERLIN—Relapse-induced escalation to a highly effective disease-modifying therapy (DMT) is associated with a reduced risk of relapses, according to comprehensive nationwide data from Danish patients with multiple sclerosis (MS). Escalation is associated with a statistically nonsignificant trend toward reduced time to first one-point worsening of Expanded Disability Status Scale (EDSS) score over the short-to-medium term. “Escalation of therapy to a highly effective DMT when patients experience relapses on a moderately effective DMT is recommended to improve control of relapse activity,” said Thor Ameri Chalmer, MD, a doctoral student at Rigshospitalet in Copenhagen, and colleagues at ECTRIMS 2018. 
Patients with relapsing-remitting MS who have relapses often switch to a new DMT. Treatment guidelines recommend switching to a highly effective DMT when a patient experiences clinical disease breakthrough. Nevertheless, patients may switch between moderately effective DMTs because of breakthrough disease or adverse effects. Dr. Chalmer and colleagues compared treatment effectiveness between highly effective DMTs and moderately effective DMTs in patients with relapsing-remitting MS who switch therapy because of relapse activity.
In this registry-based cohort study, the investigators retrieved data from the Danish MS Registry on all adults with relapsing-remitting MS. Eligible participants had an EDSS score below 6, experienced a relapse while treated with a moderately effective DMT, and consequently switched to a highly effective DMT or another moderately effective DMT. The groups were compared from treatment initiation until outcome or censoring. Censoring was defined as postbaseline switch between highly effective DMT and moderately effective DMT, cessation of therapy, relocation, or death, whichever occurred first. The primary outcomes were annualized relapse rate (ARR), relapse rate ratio, time to first relapse, and time to first one-point confirmed EDSS worsening. Dr. Chalmer and colleagues used propensity score matching to balance groups, a Cox proportional hazards model to obtain hazard ratios (HR) when modeling time to first relapse and time to first worsening, and negative binomial regression to obtain ARR and relapse rate ratios.
The matched cohort included 814 patients (407 in each group). The median follow-up time was 3.2 years. The group of patients who switched to a highly effective DMT had a 39% lower hazard rate of reaching first relapse (HR, 0.61). ARRs were 0.21 for patients who switched to a highly effective DMT and 0.34 for patients who switched to a moderately effective DMT. Relapse rate ratio for highly effective DMT compared with moderately effective DMT was 0.62. The group who switched to a highly effective DMT had 13% lower hazard rate of one-point EDSS worsening (HR, 0.87).
Switching from a moderately effective treatment to a highly effective treatment can improve outcomes.
Switching from a moderately effective treatment to a highly effective treatment can improve outcomes.
BERLIN—Relapse-induced escalation to a highly effective disease-modifying therapy (DMT) is associated with a reduced risk of relapses, according to comprehensive nationwide data from Danish patients with multiple sclerosis (MS). Escalation is associated with a statistically nonsignificant trend toward reduced time to first one-point worsening of Expanded Disability Status Scale (EDSS) score over the short-to-medium term. “Escalation of therapy to a highly effective DMT when patients experience relapses on a moderately effective DMT is recommended to improve control of relapse activity,” said Thor Ameri Chalmer, MD, a doctoral student at Rigshospitalet in Copenhagen, and colleagues at ECTRIMS 2018.
Patients with relapsing-remitting MS who have relapses often switch to a new DMT. Treatment guidelines recommend switching to a highly effective DMT when a patient experiences clinical disease breakthrough. Nevertheless, patients may switch between moderately effective DMTs because of breakthrough disease or adverse effects. Dr. Chalmer and colleagues compared treatment effectiveness between highly effective DMTs and moderately effective DMTs in patients with relapsing-remitting MS who switch therapy because of relapse activity.
In this registry-based cohort study, the investigators retrieved data from the Danish MS Registry on all adults with relapsing-remitting MS. Eligible participants had an EDSS score below 6, experienced a relapse while treated with a moderately effective DMT, and consequently switched to a highly effective DMT or another moderately effective DMT. The groups were compared from treatment initiation until outcome or censoring. Censoring was defined as postbaseline switch between highly effective DMT and moderately effective DMT, cessation of therapy, relocation, or death, whichever occurred first. The primary outcomes were annualized relapse rate (ARR), relapse rate ratio, time to first relapse, and time to first one-point confirmed EDSS worsening. Dr. Chalmer and colleagues used propensity score matching to balance groups, a Cox proportional hazards model to obtain hazard ratios (HR) when modeling time to first relapse and time to first worsening, and negative binomial regression to obtain ARR and relapse rate ratios.
The matched cohort included 814 patients (407 in each group). The median follow-up time was 3.2 years. The group of patients who switched to a highly effective DMT had a 39% lower hazard rate of reaching first relapse (HR, 0.61). ARRs were 0.21 for patients who switched to a highly effective DMT and 0.34 for patients who switched to a moderately effective DMT. Relapse rate ratio for highly effective DMT compared with moderately effective DMT was 0.62. The group who switched to a highly effective DMT had 13% lower hazard rate of one-point EDSS worsening (HR, 0.87).
BERLIN—Relapse-induced escalation to a highly effective disease-modifying therapy (DMT) is associated with a reduced risk of relapses, according to comprehensive nationwide data from Danish patients with multiple sclerosis (MS). Escalation is associated with a statistically nonsignificant trend toward reduced time to first one-point worsening of Expanded Disability Status Scale (EDSS) score over the short-to-medium term. “Escalation of therapy to a highly effective DMT when patients experience relapses on a moderately effective DMT is recommended to improve control of relapse activity,” said Thor Ameri Chalmer, MD, a doctoral student at Rigshospitalet in Copenhagen, and colleagues at ECTRIMS 2018.
Patients with relapsing-remitting MS who have relapses often switch to a new DMT. Treatment guidelines recommend switching to a highly effective DMT when a patient experiences clinical disease breakthrough. Nevertheless, patients may switch between moderately effective DMTs because of breakthrough disease or adverse effects. Dr. Chalmer and colleagues compared treatment effectiveness between highly effective DMTs and moderately effective DMTs in patients with relapsing-remitting MS who switch therapy because of relapse activity.
In this registry-based cohort study, the investigators retrieved data from the Danish MS Registry on all adults with relapsing-remitting MS. Eligible participants had an EDSS score below 6, experienced a relapse while treated with a moderately effective DMT, and consequently switched to a highly effective DMT or another moderately effective DMT. The groups were compared from treatment initiation until outcome or censoring. Censoring was defined as postbaseline switch between highly effective DMT and moderately effective DMT, cessation of therapy, relocation, or death, whichever occurred first. The primary outcomes were annualized relapse rate (ARR), relapse rate ratio, time to first relapse, and time to first one-point confirmed EDSS worsening. Dr. Chalmer and colleagues used propensity score matching to balance groups, a Cox proportional hazards model to obtain hazard ratios (HR) when modeling time to first relapse and time to first worsening, and negative binomial regression to obtain ARR and relapse rate ratios.
The matched cohort included 814 patients (407 in each group). The median follow-up time was 3.2 years. The group of patients who switched to a highly effective DMT had a 39% lower hazard rate of reaching first relapse (HR, 0.61). ARRs were 0.21 for patients who switched to a highly effective DMT and 0.34 for patients who switched to a moderately effective DMT. Relapse rate ratio for highly effective DMT compared with moderately effective DMT was 0.62. The group who switched to a highly effective DMT had 13% lower hazard rate of one-point EDSS worsening (HR, 0.87).
Migraine Elevates the Risk of Perioperative Stroke
Migraineurs are more likely to have an ischemic stroke in the 30 days after surgery, compared with patients without a history of migraine.
ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scienti
“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.
Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”
The Migraine–Stroke Connection
Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.
Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.
Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.
Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.
Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.
A Retrospective Cohort Study
Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.
The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).
The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.
Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.
In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.
Prediction Models
In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.
Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.
Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”
—Jake Remaly
Suggested Reading
Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.
Migraineurs are more likely to have an ischemic stroke in the 30 days after surgery, compared with patients without a history of migraine.
Migraineurs are more likely to have an ischemic stroke in the 30 days after surgery, compared with patients without a history of migraine.
ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scienti
“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.
Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”
The Migraine–Stroke Connection
Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.
Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.
Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.
Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.
Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.
A Retrospective Cohort Study
Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.
The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).
The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.
Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.
In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.
Prediction Models
In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.
Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.
Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”
—Jake Remaly
Suggested Reading
Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.
ASHEVILLE, NC—The 30 days after surgery are a period of exceptionally high risk for ischemic stroke, and the risk is greater for patients with migraine, compared with patients without migraine, according to a lecture at the Eighth Annual Scienti
“When we send individuals with migraine to surgery who do not have classical risk factors [for stroke], they may, in fact, still be at risk for stroke during the perioperative period,” said Timothy T. Houle, PhD, Associate Professor of Anesthesia at Massachusetts General Hospital and Harvard Medical School in Boston.
Dr. Houle described a hospital-based registry study that he and his colleagues published in BMJ. They found that the rate of ischemic stroke within 30 days of surgery was about 240 strokes per 100,000 patients without migraine, whereas among migraineurs, the rate was 430 strokes per 100,000 patients. Among patients with migraine without aura, the rate was 390 strokes per 100,000 patients, and among patients with migraine with aura, the rate was 630 strokes per 100,000 patients. “If you have migraine with aura, your risk of having a stroke is appreciably elevated and not trivial,” Dr. Houle said. “This is something to take seriously.”
The Migraine–Stroke Connection
Researchers consistently have found that migraine is associated with an increased risk of ischemic stroke in the general population, but the relationship has been challenging to study.
Possible mechanisms underlying the relationship between migraine and stroke include comorbidities (eg, higher BMI and increased cardiovascular risk factors) and medication use. In addition, research suggests that cortical spreading depression might make migraineurs’ brains more susceptible to stroke, Dr. Houle said. Patent foramen ovale, arterial dissection, coagulation dysfunction, endothelial dysfunction, or a genotype that increases the risk of migraine and stroke are other potential pathways.
Spector et al conducted a meta-analysis of 21 studies and concluded that migraine appears to be independently associated with a twofold increased risk of ischemic stroke. A meta-analysis by Schürks et al found that the relative risk of stroke was about 1.73 for patients with migraine and 2.16 for patients with migraine with aura. Migraine without aura was associated with a relative risk of 1.23, but this result was not statistically significant.
Dr. Houle and colleagues hypothesized that focusing on the perioperative period, when stroke is more prevalent, “could yield unique insights into the migraine–stroke connection,” he said.
Ischemic stroke in the perioperative period occurs at a rate of about 100 strokes per 100,000 individuals for the lowest-risk surgeries. After major cardiac and vascular surgery, the risk may be between 600 and 7,400 strokes per 100,000 individuals. “We have … a risk period that is intensely elevated for patients about to receive surgical insult,” Dr. Houle said. The increased risk may result from the indication for the surgery, as well as factors related to surgery itself, such as surgical stress, inflammatory responses, and intraoperative hypotension.
A Retrospective Cohort Study
Based on the increased risk of stroke in the general population, the investigators hypothesized that individuals with migraine also would have an elevated risk of stroke in the 30 days after surgery. They analyzed data from 124,558 patients (mean age, 52.6; 54.5% women) who underwent surgery between 2007 and 2014 at Massachusetts General Hospital and two satellite campuses. They included patients who had surgery under general anesthesia with mechanical ventilation and were successfully extubated. They used ICD-9 codes to identify patients with migraine. The primary outcome was ischemic stroke within 30 days. They identified strokes using ICD-9 codes and confirmed strokes by reviewing brain scans and medical records.
The investigators adjusted for confounders, including sex, age, BMI, emergent versus nonemergent surgery, prescriptions of antiplatelet drugs or beta blockers within four weeks before surgery, minutes of intraoperative hypotension, diabetes, hypertension, atrial fibrillation, Charleston Comorbidity Index, and work relative value units (ie, a surrogate for surgical complexity).
The cohort included 10,179 individuals with migraine (8.2%). Of the patients with migraine, 12.6% had migraine with aura.
Patients with migraine generally were younger, had higher BMI, and were more likely to be women. They were less likely to have diabetes or hypertension and to be taking antiplatelet drugs or beta blockers. Patients with migraine “were a little healthier” than the patients without migraine, Dr. Houle said.
In all, 771 patients had perioperative stroke, of whom 89 (11.5%) had migraine. About 0.6% of patients without migraine had perioperative stroke versus 0.9% of patients with migraine. The unadjusted odds ratio for stroke among migraineurs was 1.47, and the adjusted odds ratio was 1.75. “Individuals in this sample who had any migraine were at greater risk for stroke during the period after surgery, just like in the regular population,” said Dr. Houle. Although migraine without aura was not a statistically significant risk factor for stroke in the general population, it was after surgery.
Prediction Models
In one sensitivity analysis, the researchers determined each patient’s stroke risk based on known risk factors excluding migraine, such as age and cardiovascular disorders, and grouped patients by low, intermediate, and high levels of risk. Among patients in the low-risk group, the relative risk of stroke for patients with migraine versus patients without migraine was 3.5-fold higher. “These are people you would not have identified as having risk,” said Dr. Houle.
Future studies should try to identify the mechanisms involved in this relationship and assess interventions to mitigate the risk of stroke in patients with migraine who undergo surgery, Dr. Houle said.
Dr. Houle and colleagues have created a stroke prediction model that includes migraine and will “give surgeons a risk model to predict the risk of stroke for their patients,” he said. The model will “realize the risks that we uncovered in this study.”
—Jake Remaly
Suggested Reading
Schürks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-624.
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017;356:i6635.
Home-Based Therapy May Benefit Young Children With Motor Stereotypies
Teaching parents to deliver behavioral therapy via an instructional DVD may be an effective treatment approach for patients 5 and older.
CHICAGO—Home-based, parent-administered behavioral therapy supplemented by telephone contact with a therapist is effective in reducing complex motor stereotypies in children as young as 5, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. “We recommend this combined approach for children ages 5 and older,” said Harvey S. Singer, MD, Professor of Neurology at Johns Hopkins School of Medicine in Baltimore, and colleagues.
Rhythmic Movements
Motor stereotypies are repetitive, rhythmic, fixed movements that last for seconds or minutes, stop with distraction, and are thought to arise from alterations within habitual motor pathways in the brain. Complex motor stereotypies typically involve the upper extremities (eg, hand flapping and finger wiggling) and begin in early childhood. Pharmacologic therapy has not been effective, but behavioral therapy has benefited patients, Dr. Singer and colleagues said. In one study of 54 children ages 7 to 14, home-based, parent-administered behavioral therapy using an instructional DVD significantly reduced stereotypies versus baseline.
To evaluate the effectiveness of a home-based, parent-provided therapy accompanied by scheduled telephone calls with a therapist in patients ages 5 to 7 with primary complex motor stereotypies, Dr. Singer and colleagues conducted a study with 38 children (24 boys; mean age, 6).
Patients had confirmed complex motor stereotypies with onset before age 3. Patients reported no premonitory urge and had temporary suspension of movement by an external stimulus or distraction. The researchers did not exclude patients due to inattentiveness, hyperactivity, impulsivity, or obsessive-compulsive behaviors. They did exclude patients with autism spectrum disorder, evidence of intellectual disability, seizures or a known neurologic disorder, or motor or vocal tics. Primary outcome measures included the Stereotypy Severity Scale (SSS) Motor and Impairment scores and the Stereotypy Linear Analog Scale (SLAS). Secondary outcomes included Patient Global Impression of Improvement (PGI-I).
Behavioral Therapy
The investigators sent participants a 44-minute instructional DVD about complex motor stereotypies with instructions provided by a behavioral psychologist. Parents were instructed to implement awareness training in the first week and to collect data and reinforce suppression starting in Week 2. Awareness training aims to make the child aware of his or her movements by using videos showing the activity and by the practice of voluntarily starting and stopping the movement.
Fourteen of the 38 participants were lost to follow-up (ie, they completed no post-DVD receipt assessments). The intent-to-treat group included 24 participants (15 boys) who completed at least one phone call with the study psychologist after receiving the DVD. There was no difference in stereotypy severity among those who were lost to follow-up and those in the intent-to-treat group. Those lost to follow-up had higher scores on ADHD ratings, however, which “suggests those with greater ADHD symptomatology at baseline were more likely to drop out,” the researchers said.
Compared with baseline measures, participants in the intent-to-treat group had significant reductions in SSS Motor and SSS Impairment scores at the last available assessment, and outcome measures progressively improved during the study. On the PGI-I, 56.5% of participants were very much or much improved, 30% were improved, and 13% reported no change.
All primary outcome measures significantly decreased. SSS Motor scores decreased by 23% as measured by telephone and 30% as measured online, SSS Impairment scores decreased by 31% measured by telephone and 32% measured online, and SLAS decreased by 54% as measured online. “The similarity between beneficial outcomes on the SSS Motor and SSS Impairment scales suggest a positive impact on both the movements themselves and their functional impact,” Dr. Singer and colleagues said.
Teaching parents to deliver behavioral therapy via an instructional DVD may be an effective treatment approach for patients 5 and older.
Teaching parents to deliver behavioral therapy via an instructional DVD may be an effective treatment approach for patients 5 and older.
CHICAGO—Home-based, parent-administered behavioral therapy supplemented by telephone contact with a therapist is effective in reducing complex motor stereotypies in children as young as 5, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. “We recommend this combined approach for children ages 5 and older,” said Harvey S. Singer, MD, Professor of Neurology at Johns Hopkins School of Medicine in Baltimore, and colleagues.
Rhythmic Movements
Motor stereotypies are repetitive, rhythmic, fixed movements that last for seconds or minutes, stop with distraction, and are thought to arise from alterations within habitual motor pathways in the brain. Complex motor stereotypies typically involve the upper extremities (eg, hand flapping and finger wiggling) and begin in early childhood. Pharmacologic therapy has not been effective, but behavioral therapy has benefited patients, Dr. Singer and colleagues said. In one study of 54 children ages 7 to 14, home-based, parent-administered behavioral therapy using an instructional DVD significantly reduced stereotypies versus baseline.
To evaluate the effectiveness of a home-based, parent-provided therapy accompanied by scheduled telephone calls with a therapist in patients ages 5 to 7 with primary complex motor stereotypies, Dr. Singer and colleagues conducted a study with 38 children (24 boys; mean age, 6).
Patients had confirmed complex motor stereotypies with onset before age 3. Patients reported no premonitory urge and had temporary suspension of movement by an external stimulus or distraction. The researchers did not exclude patients due to inattentiveness, hyperactivity, impulsivity, or obsessive-compulsive behaviors. They did exclude patients with autism spectrum disorder, evidence of intellectual disability, seizures or a known neurologic disorder, or motor or vocal tics. Primary outcome measures included the Stereotypy Severity Scale (SSS) Motor and Impairment scores and the Stereotypy Linear Analog Scale (SLAS). Secondary outcomes included Patient Global Impression of Improvement (PGI-I).
Behavioral Therapy
The investigators sent participants a 44-minute instructional DVD about complex motor stereotypies with instructions provided by a behavioral psychologist. Parents were instructed to implement awareness training in the first week and to collect data and reinforce suppression starting in Week 2. Awareness training aims to make the child aware of his or her movements by using videos showing the activity and by the practice of voluntarily starting and stopping the movement.
Fourteen of the 38 participants were lost to follow-up (ie, they completed no post-DVD receipt assessments). The intent-to-treat group included 24 participants (15 boys) who completed at least one phone call with the study psychologist after receiving the DVD. There was no difference in stereotypy severity among those who were lost to follow-up and those in the intent-to-treat group. Those lost to follow-up had higher scores on ADHD ratings, however, which “suggests those with greater ADHD symptomatology at baseline were more likely to drop out,” the researchers said.
Compared with baseline measures, participants in the intent-to-treat group had significant reductions in SSS Motor and SSS Impairment scores at the last available assessment, and outcome measures progressively improved during the study. On the PGI-I, 56.5% of participants were very much or much improved, 30% were improved, and 13% reported no change.
All primary outcome measures significantly decreased. SSS Motor scores decreased by 23% as measured by telephone and 30% as measured online, SSS Impairment scores decreased by 31% measured by telephone and 32% measured online, and SLAS decreased by 54% as measured online. “The similarity between beneficial outcomes on the SSS Motor and SSS Impairment scales suggest a positive impact on both the movements themselves and their functional impact,” Dr. Singer and colleagues said.
CHICAGO—Home-based, parent-administered behavioral therapy supplemented by telephone contact with a therapist is effective in reducing complex motor stereotypies in children as young as 5, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. “We recommend this combined approach for children ages 5 and older,” said Harvey S. Singer, MD, Professor of Neurology at Johns Hopkins School of Medicine in Baltimore, and colleagues.
Rhythmic Movements
Motor stereotypies are repetitive, rhythmic, fixed movements that last for seconds or minutes, stop with distraction, and are thought to arise from alterations within habitual motor pathways in the brain. Complex motor stereotypies typically involve the upper extremities (eg, hand flapping and finger wiggling) and begin in early childhood. Pharmacologic therapy has not been effective, but behavioral therapy has benefited patients, Dr. Singer and colleagues said. In one study of 54 children ages 7 to 14, home-based, parent-administered behavioral therapy using an instructional DVD significantly reduced stereotypies versus baseline.
To evaluate the effectiveness of a home-based, parent-provided therapy accompanied by scheduled telephone calls with a therapist in patients ages 5 to 7 with primary complex motor stereotypies, Dr. Singer and colleagues conducted a study with 38 children (24 boys; mean age, 6).
Patients had confirmed complex motor stereotypies with onset before age 3. Patients reported no premonitory urge and had temporary suspension of movement by an external stimulus or distraction. The researchers did not exclude patients due to inattentiveness, hyperactivity, impulsivity, or obsessive-compulsive behaviors. They did exclude patients with autism spectrum disorder, evidence of intellectual disability, seizures or a known neurologic disorder, or motor or vocal tics. Primary outcome measures included the Stereotypy Severity Scale (SSS) Motor and Impairment scores and the Stereotypy Linear Analog Scale (SLAS). Secondary outcomes included Patient Global Impression of Improvement (PGI-I).
Behavioral Therapy
The investigators sent participants a 44-minute instructional DVD about complex motor stereotypies with instructions provided by a behavioral psychologist. Parents were instructed to implement awareness training in the first week and to collect data and reinforce suppression starting in Week 2. Awareness training aims to make the child aware of his or her movements by using videos showing the activity and by the practice of voluntarily starting and stopping the movement.
Fourteen of the 38 participants were lost to follow-up (ie, they completed no post-DVD receipt assessments). The intent-to-treat group included 24 participants (15 boys) who completed at least one phone call with the study psychologist after receiving the DVD. There was no difference in stereotypy severity among those who were lost to follow-up and those in the intent-to-treat group. Those lost to follow-up had higher scores on ADHD ratings, however, which “suggests those with greater ADHD symptomatology at baseline were more likely to drop out,” the researchers said.
Compared with baseline measures, participants in the intent-to-treat group had significant reductions in SSS Motor and SSS Impairment scores at the last available assessment, and outcome measures progressively improved during the study. On the PGI-I, 56.5% of participants were very much or much improved, 30% were improved, and 13% reported no change.
All primary outcome measures significantly decreased. SSS Motor scores decreased by 23% as measured by telephone and 30% as measured online, SSS Impairment scores decreased by 31% measured by telephone and 32% measured online, and SLAS decreased by 54% as measured online. “The similarity between beneficial outcomes on the SSS Motor and SSS Impairment scales suggest a positive impact on both the movements themselves and their functional impact,” Dr. Singer and colleagues said.
Which Treatments Are Effective Against Intractable Cluster Headache?
Current and emerging therapies may reduce the social, economic, and psychiatric burden of this painful disorder.
ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.
Making the Diagnosis
The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.
Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.
The European Headache Federation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.
Reasons for Intractability
One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”
Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.
Established and Emerging Acute Treatments
The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.
Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.
In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.
In 2017, the FDA cleared gammaCore, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.
In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.
Preventive Treatment Is Essential
“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.
Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.
Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.
Other Treatments May Be Effective
The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.
Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.
Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.
Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.
—Erik Greb
Suggested Reading
Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.
Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.
Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.
Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.
Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
Current and emerging therapies may reduce the social, economic, and psychiatric burden of this painful disorder.
Current and emerging therapies may reduce the social, economic, and psychiatric burden of this painful disorder.
ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.
Making the Diagnosis
The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.
Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.
The European Headache Federation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.
Reasons for Intractability
One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”
Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.
Established and Emerging Acute Treatments
The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.
Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.
In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.
In 2017, the FDA cleared gammaCore, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.
In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.
Preventive Treatment Is Essential
“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.
Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.
Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.
Other Treatments May Be Effective
The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.
Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.
Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.
Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.
—Erik Greb
Suggested Reading
Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.
Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.
Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.
Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.
Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
ASHEVILLE, NC—Patients with intractable cluster headache present an urgent challenge to neurologists. The disorder is associated with “the worst pain you can experience,” and most patients have suicidal ideation, said Todd Rozen, MD, a neurologist at Mayo Clinic in Jacksonville, Florida. To help these patients, it is necessary to confirm the diagnosis, conduct proper evaluations for secondary mimics, and choose the most appropriate and effective treatments, he said at the Eighth Annual Scientific Meeting of the Southern Headache Society.
Making the Diagnosis
The current diagnostic criteria for cluster headache include severe unilateral orbital, supraorbital, or temporal pain that lasts for 15 minutes to 180 minutes when untreated. Patients may have conjunctival injection, lacrimation, rhinorrhea, or a sense of restlessness. Most patients have between one and three attacks per day, and the average attack lasts from 60 minutes to 75 minutes, said Dr. Rozen. Migrainous features such as photophobia, phonophobia, and nausea are common in cluster headache, but should not affect the diagnosis. If the duration and frequency of attacks are consistent with cluster headache, then that is the correct diagnosis, said Dr. Rozen.
Like migraine, cluster headache may be episodic or chronic. Episodic cluster headache is more likely to remit than chronic cluster headache, but the former may transition to the latter.
The European Headache Federation has defined treatment-refractory cluster headache as cluster headache that fails to respond to more than three typical preventive medicines. Regardless of whether the disorder is episodic or chronic for a given patient, it may become intractable, said Dr. Rozen.
Reasons for Intractability
One potential reason for intractability is an incorrect diagnosis. Cluster headache is a trigeminal autonomic cephalalgia (TAC), and a person with a diagnosis of intractable cluster headache may in fact have a different TAC. The TACs form a spectrum, and a patient’s disorder may change from cluster headache to paroxysmal hemicrania, for example, said Dr. Rozen. “Always think of [attack] duration and frequency to make your diagnosis.”
Another potential reason for intractability is that the headache is secondary to a lesion. The secondary headache disorders often mimic the primary headache disorders, but do not respond to typical medications. The three most common causes of secondary cluster headache are secretory pituitary tumors, carotid dissections, and cavernous sinus lesions. “Every cluster patient … deserves a brain MRI with or without the pituitary cuts, an MR angiogram (both head and neck with dissection protocol), and pituitary hormones,” said Dr. Rozen.
Established and Emerging Acute Treatments
The most common acute treatments for cluster headache are sumatriptan injection or nasal spray and high-flow oxygen. Most patients respond to these treatments, but for those who do not, neurologists may consider options such as dihydroergotamine (DHE) injection, ergotamines, intranasal lidocaine, olanzapine, chlorpromazine suppository, and indomethacin suppository. Data from the US Cluster Headache Survey, however, indicate that less than 45% of patients respond to these treatments.
Most patients with cluster headache do not respond to oral acute medications because they have slow onsets of action. An exception is zolmitriptan, which is administered in a 10-mg dose, as opposed to the traditional 5-mg oral dose. Another acute nonmedicinal therapy is a suboccipital nerve block, which often terminates a headache within a minute, said Dr. Rozen.
In addition, new acute treatments for cluster headache have emerged. One is the delivery of oxygen by demand valve, which provides oxygen according to the user’s respiration rate and tidal volume. Unlike previous delivery methods, which deliver a small amount of ambient air, the demand valve delivers 100% pure oxygen. The demand valve also allows hyperventilation, which may be crucial for effective treatment, said Dr. Rozen. Several studies have suggested that demand-valve oxygen may be more effective than the typically prescribed continuous-flow oxygen administered through a nonrebreather face mask.
In 2017, the FDA cleared gammaCore, a noninvasive vagus nerve stimulation (VNS) device, for the acute treatment of episodic cluster headache. Patients can use the device to deliver two-minute doses of stimulation through a conductive gel applied to the neck. The treatment may be considered for patients who have not responded to other acute medications, said Dr. Rozen.
In a study by Schoenen and colleagues, 67% of patients with chronic cluster headache who were treated with on-demand sphenopalatine ganglion stimulation achieved pain relief. In comparison, 7% of patients who received sham treatment achieved pain relief. Sphenopalatine ganglion stimulation is not approved in the United States, however.
Preventive Treatment Is Essential
“It is absolutely key to treat cluster headaches with preventives unless [the patients] have two- to three-week cycles [of attacks],” said Dr. Rozen. Verapamil, lithium, valproic acid, daily corticosteroids, topiramate, melatonin, and methylergonovine can be used for the prevention of cluster headache attacks. Daily corticosteroids are appropriate if the patient’s cycles last for two to three weeks, said Dr. Rozen. Topiramate appears to be more effective in women with cluster headache than men.
Until a patient has failed to respond to all of these preventive treatments, it may be inappropriate to describe his or her disorder as refractory, said Dr. Rozen. If a patient partially responds to one preventive therapy, another can be added. Combination therapy for cluster headache is common, and as many as three medications can be administered concomitantly, said Dr. Rozen. Unlike for other headache disorders, doses for cluster headache can be raised to high levels.
Data from the US Cluster Headache Survey, though, show that less than half of patients respond to preventive treatments. In addition, more than 70% of respondents had never received any preventive treatment, “which is quite scary for such a horrible disorder,” said Dr. Rozen.
Other Treatments May Be Effective
The literature provides a small amount of evidence to support additional treatments for cluster headache. Three studies have indicated a benefit of daily treatment with triptans, particularly frovatriptan, said Dr. Rozen. Data also support transdermal clonidine, indomethacin, and intranasal civamide. “Gabapentin is a wonderful add-on therapy. It is not good as a primary therapy,” said Dr. Rozen. Neurologists also may choose baclofen or mycophenolate mofetil.
Reports indicate that sodium oxybate can alleviate episodic and chronic cluster headache, especially if the patient has multiple nocturnal headaches, said Dr. Rozen. Three trials have examined hyperbaric oxygen, and a placebo-controlled trial found a benefit of warfarin. Rozen, and later Nobre et al, reported that clomiphene was effective and could change the pattern of cluster headache attacks.
Between 40% and 50% of patients respond to a single suboccipital nerve block as preventive therapy. Dr. Rozen has reported on high-volume suboccipital nerve blocks that administer 9 cm3 of 1% lidocaine and a small amount of corticosteroid. This treatment has “an excellent preventive effect in chronic refractory cluster headache,” he added. “Most of these patients have failed eight to 10 preventive [treatments]…. If you fail block one, you will most likely not respond to blocks.” Many patients who respond to this block could respond well to greater occipital nerve stimulation, but it is not easy to get insurance coverage for this treatment, said Dr. Rozen.
Finally, a new class of medications may be approved for cluster headache prevention. The monoclonal calcitonin gene-related peptide antibodies, which have been approved for migraine prevention, appear to be effective for episodic cluster headache in clinical trials. These treatments may not show efficacy for chronic cluster headache, however.
—Erik Greb
Suggested Reading
Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-2457.
Nobre ME, Peres MFP, Moreira PF Filho, Leal AJ. Clomiphene treatment may be effective in refractory episodic and chronic cluster headache. Arq Neuropsiquiatr. 2017;75(9):620-624.
Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52(1):99-113.
Rozen TD, Fishman RS. Demand valve oxygen: a promising new oxygen delivery system for the acute treatment of cluster headache. Pain Med. 2013;14(4):455-459.
Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-830.
Study confirms advice to halt methotrexate when giving flu vaccine to RA patients
CHICAGO – Discontinuing methotrexate for 2 weeks in patients with RA starting the day they receive the seasonal influenza vaccine significantly improves the vaccine’s immunogenicity without aggravating disease activity, Kevin L. Winthrop, MD, reported at the annual meeting of the American College of Rheumatology.
“I think this is potentially clinically practice changing because now there are two studies showing the same thing,” said Dr. Winthrop, a professor of public health and preventive medicine at Oregon Health & Science University, Portland.
Based upon these prospective randomized studies, which he conducted together with investigators at Seoul National University in South Korea, initiating a 2-week halt of methotrexate on the day the influenza vaccine is given to patients with RA is now his routine practice, and he recommends other physicians do the same.
The first prospective, randomized trial included 199 RA patients on stable doses of methotrexate who were assigned to one of four groups in conjunction with seasonal influenza vaccination. One group continued their methotrexate as usual, the second stopped the drug for 1 month prior to vaccination and then restarted it at the time of vaccination, the third group halted methotrexate for 2 weeks before and 2 weeks after vaccination, and the fourth suspended methotrexate for 4 weeks starting on the day they got their flu shot. Everyone received trivalent influenza vaccine containing H1N1, H3N2, and B/Yamagata.
The lowest rate of satisfactory vaccine response as defined by at least a 300% titer increase 1 month after vaccination occurred in the group that continued their methotrexate as usual. The group that halted the drug for 2 weeks before and 2 weeks after influenza vaccination had a 51% satisfactory vaccine response against all three antigens, compared with a 31.5% rate in the methotrexate-as-usual group. RA flare rates ranged from 21% to 39% across the four study arms, differences that weren’t statistically significant (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).
Next Dr. Winthrop and his colleagues conducted a confirmatory prospective, multicenter, randomized trial in which they sought to nail down the optimal duration and timing of methotrexate discontinuation. A total of 320 RA patients on stable doses of methotrexate were assigned to halt the drug for 2 weeks starting at the time they received a quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains, or to continue their methotrexate throughout.
A satisfactory vaccine response was achieved in 75.5% of the group that discontinued the drug, significantly better than the 54.5% rate in the methotrexate continuers. The absolute difference in seroprotection was greater in patients who halted their methotrexate for 2 weeks after vaccination for all four antigens: an absolute 11% difference for H1N1, 16% for H3N2, 12% for B/Yamagata, and 15% for B/Victoria (Ann Rheum Dis. 2018 Jun;77[6]:898-904).
“It does seem to be a nice strategy. The percentage of people who flared their RA during their 2 weeks off methotrexate was very low, so there seems to be a good reason to do this,” according to Dr. Winthrop.
Some rheumatologists he has spoken with initially balked at the plausibility of the results.
“I had the same thought about these studies: It doesn’t make sense to me in terms of how methotrexate works, and why we would see this effect acutely by stopping methotrexate for just 2 weeks?” he said.
But then a coinvestigator drilled down deeper into the data and came up with the explanation: The benefit in terms of enhanced flu vaccine immunogenicity through temporary withholding of methotrexate was confined to the subgroup of RA patients with high baseline levels of B-cell activation factor (BAFF). In contrast, withholding methotrexate didn’t affect the vaccine response in patients with low or normal baseline BAFF (Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214025).
“I don’t know how to check anyone’s BAFF levels. I don’t think there’s a commercial test out there. But this does help explain why we saw this observation. So I think I would still hold everyone’s methotrexate for 2 weeks. That’s how I approach it. And they may get benefit from it, and they may not,” he said.
Dr. Winthrop reported having no financial conflicts regarding the study, which was funded by GC Pharma.
CHICAGO – Discontinuing methotrexate for 2 weeks in patients with RA starting the day they receive the seasonal influenza vaccine significantly improves the vaccine’s immunogenicity without aggravating disease activity, Kevin L. Winthrop, MD, reported at the annual meeting of the American College of Rheumatology.
“I think this is potentially clinically practice changing because now there are two studies showing the same thing,” said Dr. Winthrop, a professor of public health and preventive medicine at Oregon Health & Science University, Portland.
Based upon these prospective randomized studies, which he conducted together with investigators at Seoul National University in South Korea, initiating a 2-week halt of methotrexate on the day the influenza vaccine is given to patients with RA is now his routine practice, and he recommends other physicians do the same.
The first prospective, randomized trial included 199 RA patients on stable doses of methotrexate who were assigned to one of four groups in conjunction with seasonal influenza vaccination. One group continued their methotrexate as usual, the second stopped the drug for 1 month prior to vaccination and then restarted it at the time of vaccination, the third group halted methotrexate for 2 weeks before and 2 weeks after vaccination, and the fourth suspended methotrexate for 4 weeks starting on the day they got their flu shot. Everyone received trivalent influenza vaccine containing H1N1, H3N2, and B/Yamagata.
The lowest rate of satisfactory vaccine response as defined by at least a 300% titer increase 1 month after vaccination occurred in the group that continued their methotrexate as usual. The group that halted the drug for 2 weeks before and 2 weeks after influenza vaccination had a 51% satisfactory vaccine response against all three antigens, compared with a 31.5% rate in the methotrexate-as-usual group. RA flare rates ranged from 21% to 39% across the four study arms, differences that weren’t statistically significant (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).
Next Dr. Winthrop and his colleagues conducted a confirmatory prospective, multicenter, randomized trial in which they sought to nail down the optimal duration and timing of methotrexate discontinuation. A total of 320 RA patients on stable doses of methotrexate were assigned to halt the drug for 2 weeks starting at the time they received a quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains, or to continue their methotrexate throughout.
A satisfactory vaccine response was achieved in 75.5% of the group that discontinued the drug, significantly better than the 54.5% rate in the methotrexate continuers. The absolute difference in seroprotection was greater in patients who halted their methotrexate for 2 weeks after vaccination for all four antigens: an absolute 11% difference for H1N1, 16% for H3N2, 12% for B/Yamagata, and 15% for B/Victoria (Ann Rheum Dis. 2018 Jun;77[6]:898-904).
“It does seem to be a nice strategy. The percentage of people who flared their RA during their 2 weeks off methotrexate was very low, so there seems to be a good reason to do this,” according to Dr. Winthrop.
Some rheumatologists he has spoken with initially balked at the plausibility of the results.
“I had the same thought about these studies: It doesn’t make sense to me in terms of how methotrexate works, and why we would see this effect acutely by stopping methotrexate for just 2 weeks?” he said.
But then a coinvestigator drilled down deeper into the data and came up with the explanation: The benefit in terms of enhanced flu vaccine immunogenicity through temporary withholding of methotrexate was confined to the subgroup of RA patients with high baseline levels of B-cell activation factor (BAFF). In contrast, withholding methotrexate didn’t affect the vaccine response in patients with low or normal baseline BAFF (Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214025).
“I don’t know how to check anyone’s BAFF levels. I don’t think there’s a commercial test out there. But this does help explain why we saw this observation. So I think I would still hold everyone’s methotrexate for 2 weeks. That’s how I approach it. And they may get benefit from it, and they may not,” he said.
Dr. Winthrop reported having no financial conflicts regarding the study, which was funded by GC Pharma.
CHICAGO – Discontinuing methotrexate for 2 weeks in patients with RA starting the day they receive the seasonal influenza vaccine significantly improves the vaccine’s immunogenicity without aggravating disease activity, Kevin L. Winthrop, MD, reported at the annual meeting of the American College of Rheumatology.
“I think this is potentially clinically practice changing because now there are two studies showing the same thing,” said Dr. Winthrop, a professor of public health and preventive medicine at Oregon Health & Science University, Portland.
Based upon these prospective randomized studies, which he conducted together with investigators at Seoul National University in South Korea, initiating a 2-week halt of methotrexate on the day the influenza vaccine is given to patients with RA is now his routine practice, and he recommends other physicians do the same.
The first prospective, randomized trial included 199 RA patients on stable doses of methotrexate who were assigned to one of four groups in conjunction with seasonal influenza vaccination. One group continued their methotrexate as usual, the second stopped the drug for 1 month prior to vaccination and then restarted it at the time of vaccination, the third group halted methotrexate for 2 weeks before and 2 weeks after vaccination, and the fourth suspended methotrexate for 4 weeks starting on the day they got their flu shot. Everyone received trivalent influenza vaccine containing H1N1, H3N2, and B/Yamagata.
The lowest rate of satisfactory vaccine response as defined by at least a 300% titer increase 1 month after vaccination occurred in the group that continued their methotrexate as usual. The group that halted the drug for 2 weeks before and 2 weeks after influenza vaccination had a 51% satisfactory vaccine response against all three antigens, compared with a 31.5% rate in the methotrexate-as-usual group. RA flare rates ranged from 21% to 39% across the four study arms, differences that weren’t statistically significant (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).
Next Dr. Winthrop and his colleagues conducted a confirmatory prospective, multicenter, randomized trial in which they sought to nail down the optimal duration and timing of methotrexate discontinuation. A total of 320 RA patients on stable doses of methotrexate were assigned to halt the drug for 2 weeks starting at the time they received a quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains, or to continue their methotrexate throughout.
A satisfactory vaccine response was achieved in 75.5% of the group that discontinued the drug, significantly better than the 54.5% rate in the methotrexate continuers. The absolute difference in seroprotection was greater in patients who halted their methotrexate for 2 weeks after vaccination for all four antigens: an absolute 11% difference for H1N1, 16% for H3N2, 12% for B/Yamagata, and 15% for B/Victoria (Ann Rheum Dis. 2018 Jun;77[6]:898-904).
“It does seem to be a nice strategy. The percentage of people who flared their RA during their 2 weeks off methotrexate was very low, so there seems to be a good reason to do this,” according to Dr. Winthrop.
Some rheumatologists he has spoken with initially balked at the plausibility of the results.
“I had the same thought about these studies: It doesn’t make sense to me in terms of how methotrexate works, and why we would see this effect acutely by stopping methotrexate for just 2 weeks?” he said.
But then a coinvestigator drilled down deeper into the data and came up with the explanation: The benefit in terms of enhanced flu vaccine immunogenicity through temporary withholding of methotrexate was confined to the subgroup of RA patients with high baseline levels of B-cell activation factor (BAFF). In contrast, withholding methotrexate didn’t affect the vaccine response in patients with low or normal baseline BAFF (Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214025).
“I don’t know how to check anyone’s BAFF levels. I don’t think there’s a commercial test out there. But this does help explain why we saw this observation. So I think I would still hold everyone’s methotrexate for 2 weeks. That’s how I approach it. And they may get benefit from it, and they may not,” he said.
Dr. Winthrop reported having no financial conflicts regarding the study, which was funded by GC Pharma.
REPORTING FROM THE ACR ANNUAL MEETING
FDA approves elotuzumab with pom/dex in refractory myeloma
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
The who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Elotuzumab is already approved in combination with lenalidomide and dexamethasone to treat adult myeloma patients who have received one to three prior therapies.
The FDA’s latest approval of elotuzumab is based on results from ELOQUENT-3. This phase 2 trial enrolled multiple myeloma patients who had refractory or relapsed disease and had received both lenalidomide and a proteasome inhibitor.
In the trial, patients were randomized to receive elotuzumab plus pomalidomide and dexamethasone (EPd, n = 60) or pomalidomide and dexamethasone (Pd, n = 57) in 28-day cycles until disease progression or unacceptable toxicity.
The overall response rate was 53.3% in the EPd arm and 26.3% in the Pd arm (P = .0029); the rate of complete response or stringent complete response was 8.3% and 1.8%, respectively.
Median progression-free survival was 10.25 months with EPd and 4.67 months with Pd (P = .0078).
Serious adverse events occurred in 22% of patients in the EPd arm and 15% in the Pd arm. The most frequent serious adverse events were pneumonia and respiratory tract infection.
Additional results from ELOQUENT-3 can be found in the full prescribing information for elotuzumab, which is available on the Empliciti website.
Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
BNP levels and mortality in patients with and without heart failure
Clinical question: Does B-type natriuretic peptide (BNP) have prognostic value outside of heart failure (HF) patients?
Background: BNP levels are influenced by both cardiac and extracardiac stimuli and thus might have prognostic value outside of the traditional use to guide therapy for HF patients.
Study design: Retrospective cohort study of the Vanderbilt electronic health record.
Setting: Vanderbilt University Medical Center, Nashville, Tenn.
Synopsis: The study evaluated 30,487 patients with at least two BNP values for 2002-2015. Within this cohort, 62% of patients did not have a HF diagnosis. Risk of death was elevated in all patients regardless of HF status as BNP values rose. An increase from the 25th to 75th percentile in BNP value was associated with an increased risk of death in non-HF patients (hazard ratio, 2.08; 95% confidence interval, 1.99-2.2). Additionally, in a multivariate analysis BNP was the strongest predictor of death, compared with traditional risk factors in both HF and non-HF patients. The main limitation to this study was the use of ICD codes for diagnosis of HF.
Bottom line: BNP has predictive value for risk of death in non-HF patients; as BNP levels rise, regardless of HF status, so does risk of death.
Citation: York MK et al. B-type natriuretic peptide levels and mortality in patients with and without heart failure. J Am Coll Cardiol. 2018 May 15;71(19):2079-88.
Dr. Abramowicz is an assistant professor in the division of hospital medicine, University of Colorado, Denver.
Clinical question: Does B-type natriuretic peptide (BNP) have prognostic value outside of heart failure (HF) patients?
Background: BNP levels are influenced by both cardiac and extracardiac stimuli and thus might have prognostic value outside of the traditional use to guide therapy for HF patients.
Study design: Retrospective cohort study of the Vanderbilt electronic health record.
Setting: Vanderbilt University Medical Center, Nashville, Tenn.
Synopsis: The study evaluated 30,487 patients with at least two BNP values for 2002-2015. Within this cohort, 62% of patients did not have a HF diagnosis. Risk of death was elevated in all patients regardless of HF status as BNP values rose. An increase from the 25th to 75th percentile in BNP value was associated with an increased risk of death in non-HF patients (hazard ratio, 2.08; 95% confidence interval, 1.99-2.2). Additionally, in a multivariate analysis BNP was the strongest predictor of death, compared with traditional risk factors in both HF and non-HF patients. The main limitation to this study was the use of ICD codes for diagnosis of HF.
Bottom line: BNP has predictive value for risk of death in non-HF patients; as BNP levels rise, regardless of HF status, so does risk of death.
Citation: York MK et al. B-type natriuretic peptide levels and mortality in patients with and without heart failure. J Am Coll Cardiol. 2018 May 15;71(19):2079-88.
Dr. Abramowicz is an assistant professor in the division of hospital medicine, University of Colorado, Denver.
Clinical question: Does B-type natriuretic peptide (BNP) have prognostic value outside of heart failure (HF) patients?
Background: BNP levels are influenced by both cardiac and extracardiac stimuli and thus might have prognostic value outside of the traditional use to guide therapy for HF patients.
Study design: Retrospective cohort study of the Vanderbilt electronic health record.
Setting: Vanderbilt University Medical Center, Nashville, Tenn.
Synopsis: The study evaluated 30,487 patients with at least two BNP values for 2002-2015. Within this cohort, 62% of patients did not have a HF diagnosis. Risk of death was elevated in all patients regardless of HF status as BNP values rose. An increase from the 25th to 75th percentile in BNP value was associated with an increased risk of death in non-HF patients (hazard ratio, 2.08; 95% confidence interval, 1.99-2.2). Additionally, in a multivariate analysis BNP was the strongest predictor of death, compared with traditional risk factors in both HF and non-HF patients. The main limitation to this study was the use of ICD codes for diagnosis of HF.
Bottom line: BNP has predictive value for risk of death in non-HF patients; as BNP levels rise, regardless of HF status, so does risk of death.
Citation: York MK et al. B-type natriuretic peptide levels and mortality in patients with and without heart failure. J Am Coll Cardiol. 2018 May 15;71(19):2079-88.
Dr. Abramowicz is an assistant professor in the division of hospital medicine, University of Colorado, Denver.
A Method to His Madness
ANSWER
The correct interpretation includes sinus tachycardia with biatrial enlargement and ST- and T-wave abnormalities consistent with inferolateral ischemia.
Sinus tachycardia is evident from an atrial rate > 100 beats/min, with a consistent PR interval for each P and R wave.
Criteria for right atrial enlargement include tall P waves in leads II, III, and aVF, and for left atrial enlargement, P waves in lead I ≥ 110 ms with terminal negativity of the P wave in lead V1 ≥ 1 mm2. When both criteria are met, the diagnosis is biatrial enlargement.
The presence of ST elevation in lead V4 and T-wave inversions in leads V5 and V6 and limb leads II, III, and aVF suggest inferolateral ischemia.
ANSWER
The correct interpretation includes sinus tachycardia with biatrial enlargement and ST- and T-wave abnormalities consistent with inferolateral ischemia.
Sinus tachycardia is evident from an atrial rate > 100 beats/min, with a consistent PR interval for each P and R wave.
Criteria for right atrial enlargement include tall P waves in leads II, III, and aVF, and for left atrial enlargement, P waves in lead I ≥ 110 ms with terminal negativity of the P wave in lead V1 ≥ 1 mm2. When both criteria are met, the diagnosis is biatrial enlargement.
The presence of ST elevation in lead V4 and T-wave inversions in leads V5 and V6 and limb leads II, III, and aVF suggest inferolateral ischemia.
ANSWER
The correct interpretation includes sinus tachycardia with biatrial enlargement and ST- and T-wave abnormalities consistent with inferolateral ischemia.
Sinus tachycardia is evident from an atrial rate > 100 beats/min, with a consistent PR interval for each P and R wave.
Criteria for right atrial enlargement include tall P waves in leads II, III, and aVF, and for left atrial enlargement, P waves in lead I ≥ 110 ms with terminal negativity of the P wave in lead V1 ≥ 1 mm2. When both criteria are met, the diagnosis is biatrial enlargement.
The presence of ST elevation in lead V4 and T-wave inversions in leads V5 and V6 and limb leads II, III, and aVF suggest inferolateral ischemia.
A 34-year-old man with a history of malignant hypertension is brought to the emergency department via ACLS ambulance with substernal chest pain and a field blood pressure of 228/136 mm Hg. According to the paramedics, the patient’s symptoms include dyspnea, emotional lability, agitation, and violent behavior requiring physical restraints.
The patient is known at your institution (and many others in the area) for his frequent admissions and poor compliance with medications. Today, the patient’s agitation and paranoia prevent you from obtaining a clear history of the present illness. You do learn that he recently started working in a meth lab, where he has had free access to illicit substances.
His toxicology screen is positive for methamphetamines, cocaine, and phencyclidine. Additional lab tests indicate elevated serial troponin levels, diagnostic of non-ST-segment elevation myocardial infarction (NSTEMI), and an elevated B-type natriuretic peptide level, compatible with congestive
A review of his electronic medical record reveals allergies to sulfa and erythromycin. His medication list includes carvedilol (6.25 mg bid), furosemide (40 mg/d), and lisinopril (20 mg bid), with multiple references to noncompliance. You also note that he has had several skin and soft-tissue infections requiring both oral and IV antibiotic therapy.
The patient’s vital signs on arrival include a blood pressure of 210/140 mm Hg; pulse, 110 beats/min; respiratory rate, 20 breaths/min-1; and temperature, 38.2°C. His weight is 147 lb and his height, 69 in.
Physical exam reveals a man who appears agitated, restless, and psychotic. His skin is remarkable for multiple excoriated lesions on both upper and lower extremities. Recent needle tracks are present in both antecubital fossae.
The HEENT exam is remarkable for enlarged pupils and exophthalmos. Punctate lesions are seen on the nasal septum, and the teeth are in poor repair with multiple caries. The neck is supple, with a palpable thyroid and no evidence of jugular venous distention.
Pulmonary sounds reveal coarse rhonchi in both bases, with no evidence of wheezing. The cardiac exam reveals tachycardia with a regular rate and no extra heart sounds or murmurs. Peripheral pulses are strong and equal bilaterally. The abdominal exam is remarkable for diffuse tenderness to palpation without focal pain, as well as a firm liver edge 2 cm below the right costal margin. The neurologic exam is remarkable for agitation, paranoia, and psychosis. There are no focal cranial nerve defects.
Workup—including chest and abdominal CT, echocardiogram, and ECG—is ordered. The ECG reveals a ventricular rate of 105 beats/min; PR interval, 170 ms; QRS duration, 96 ms; QT/QTc interval, 362/478 ms; P axis, 54°; R axis, 81°; and T axis, –59°. What is your interpretation?
Needle aspiration comes first for most breast abscesses
BOSTON – When surgeon Wendy R. Greene, MD, FACS, director of acute and critical care surgery at Emory University, Atlanta, asked a room of about 300 general surgeons at the annual clinical congress of the American College of Surgeons how many use needle aspiration first for breast abscesses, and how many use a scalpel, it was about a 50-50 split.
This divided response is why Dr. Greene addressed in her presentation the right approach to the problem of breast abscesses. In short, “for run-of-the-mill abscesses less than 5 cm, don’t get out the scalpel; get out the needle first,” she said.
New mothers over age 30 years are most at risk, especially if they are past 40 weeks’ gestation.
There certainly are indications for the scalpel first. If the skin overlaying the abscess is dead, shiny, sloughing off, or leaking pus, or if the abscess is larger than 5 cm on ultrasound, a small stab incision is in order, and it should be made at the maximum point of fluctuation, after numbing the surrounding tissue. Put a wipe in place to catch the pus, debride as necessary, and “irrigate, irrigate, irrigate,” Dr. Greene said.
She uses suction to make sure all the pus is out, then injects a lidocaine into the cavity for pain control and lets it rest a few minutes before another round of suction.
Septic, deteriorating patients, and the immunocompromised, need a larger incision and drainage, with IV antibiotics in the hospital, but even in those cases, “avoid placing percutaneous drains; there’s rarely a role for them in modern management of breast abscesses.” Women will have poorer results and poorer cosmesis, Dr. Greene said.
Aggressive drainage isn’t necessary most of the time, and it can destroy healthy tissue and leave new mothers with breastfeeding problems and milk fistulas. There’s also a risk for scarring, deformity, and loss of the ability to lactate.
An 18-21 gauge needle with local anesthetic is usually enough. The lesion should be obvious on ultrasound, and it’s useful to guide the needle and ensure the cavity collapses on aspiration.
Dr. Greene said it also is important to culture milk in new mothers, and culture her infant’s nose and mouth, because cracked skin on the breast can let germs from nursing into the milk ducts.
Women are sent home after aspiration with antibiotics for 7-10 days, ones that are safe for nursing infants. They might be back with another abscess in a few weeks, so it’s important to be patient and ready for ongoing treatment.
The ultimate worry with recurrent cases is that a breast mass is blocking a milk duct, so mammography is often in order for repeat patients, especially with a family history of breast cancer. Wait until the acute infection has died down; a mammograph can be too painful otherwise, Dr. Greene said.
In the meantime, let infants nurse. They “are a great way to help drain the breast,” she said.
Dr. Greene had no relevant disclosures.
BOSTON – When surgeon Wendy R. Greene, MD, FACS, director of acute and critical care surgery at Emory University, Atlanta, asked a room of about 300 general surgeons at the annual clinical congress of the American College of Surgeons how many use needle aspiration first for breast abscesses, and how many use a scalpel, it was about a 50-50 split.
This divided response is why Dr. Greene addressed in her presentation the right approach to the problem of breast abscesses. In short, “for run-of-the-mill abscesses less than 5 cm, don’t get out the scalpel; get out the needle first,” she said.
New mothers over age 30 years are most at risk, especially if they are past 40 weeks’ gestation.
There certainly are indications for the scalpel first. If the skin overlaying the abscess is dead, shiny, sloughing off, or leaking pus, or if the abscess is larger than 5 cm on ultrasound, a small stab incision is in order, and it should be made at the maximum point of fluctuation, after numbing the surrounding tissue. Put a wipe in place to catch the pus, debride as necessary, and “irrigate, irrigate, irrigate,” Dr. Greene said.
She uses suction to make sure all the pus is out, then injects a lidocaine into the cavity for pain control and lets it rest a few minutes before another round of suction.
Septic, deteriorating patients, and the immunocompromised, need a larger incision and drainage, with IV antibiotics in the hospital, but even in those cases, “avoid placing percutaneous drains; there’s rarely a role for them in modern management of breast abscesses.” Women will have poorer results and poorer cosmesis, Dr. Greene said.
Aggressive drainage isn’t necessary most of the time, and it can destroy healthy tissue and leave new mothers with breastfeeding problems and milk fistulas. There’s also a risk for scarring, deformity, and loss of the ability to lactate.
An 18-21 gauge needle with local anesthetic is usually enough. The lesion should be obvious on ultrasound, and it’s useful to guide the needle and ensure the cavity collapses on aspiration.
Dr. Greene said it also is important to culture milk in new mothers, and culture her infant’s nose and mouth, because cracked skin on the breast can let germs from nursing into the milk ducts.
Women are sent home after aspiration with antibiotics for 7-10 days, ones that are safe for nursing infants. They might be back with another abscess in a few weeks, so it’s important to be patient and ready for ongoing treatment.
The ultimate worry with recurrent cases is that a breast mass is blocking a milk duct, so mammography is often in order for repeat patients, especially with a family history of breast cancer. Wait until the acute infection has died down; a mammograph can be too painful otherwise, Dr. Greene said.
In the meantime, let infants nurse. They “are a great way to help drain the breast,” she said.
Dr. Greene had no relevant disclosures.
BOSTON – When surgeon Wendy R. Greene, MD, FACS, director of acute and critical care surgery at Emory University, Atlanta, asked a room of about 300 general surgeons at the annual clinical congress of the American College of Surgeons how many use needle aspiration first for breast abscesses, and how many use a scalpel, it was about a 50-50 split.
This divided response is why Dr. Greene addressed in her presentation the right approach to the problem of breast abscesses. In short, “for run-of-the-mill abscesses less than 5 cm, don’t get out the scalpel; get out the needle first,” she said.
New mothers over age 30 years are most at risk, especially if they are past 40 weeks’ gestation.
There certainly are indications for the scalpel first. If the skin overlaying the abscess is dead, shiny, sloughing off, or leaking pus, or if the abscess is larger than 5 cm on ultrasound, a small stab incision is in order, and it should be made at the maximum point of fluctuation, after numbing the surrounding tissue. Put a wipe in place to catch the pus, debride as necessary, and “irrigate, irrigate, irrigate,” Dr. Greene said.
She uses suction to make sure all the pus is out, then injects a lidocaine into the cavity for pain control and lets it rest a few minutes before another round of suction.
Septic, deteriorating patients, and the immunocompromised, need a larger incision and drainage, with IV antibiotics in the hospital, but even in those cases, “avoid placing percutaneous drains; there’s rarely a role for them in modern management of breast abscesses.” Women will have poorer results and poorer cosmesis, Dr. Greene said.
Aggressive drainage isn’t necessary most of the time, and it can destroy healthy tissue and leave new mothers with breastfeeding problems and milk fistulas. There’s also a risk for scarring, deformity, and loss of the ability to lactate.
An 18-21 gauge needle with local anesthetic is usually enough. The lesion should be obvious on ultrasound, and it’s useful to guide the needle and ensure the cavity collapses on aspiration.
Dr. Greene said it also is important to culture milk in new mothers, and culture her infant’s nose and mouth, because cracked skin on the breast can let germs from nursing into the milk ducts.
Women are sent home after aspiration with antibiotics for 7-10 days, ones that are safe for nursing infants. They might be back with another abscess in a few weeks, so it’s important to be patient and ready for ongoing treatment.
The ultimate worry with recurrent cases is that a breast mass is blocking a milk duct, so mammography is often in order for repeat patients, especially with a family history of breast cancer. Wait until the acute infection has died down; a mammograph can be too painful otherwise, Dr. Greene said.
In the meantime, let infants nurse. They “are a great way to help drain the breast,” she said.
Dr. Greene had no relevant disclosures.
EXPERT ANALYSIS FROM THE ACS CLINICAL CONGRESS