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

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

Emerging technologies: Worth the cost?

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

Cost will drive innovation

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

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

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

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

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

–Heidi Splete contributed to this article.

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

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

Emerging technologies: Worth the cost?

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

Cost will drive innovation

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

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

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

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

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

–Heidi Splete contributed to this article.

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

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

Emerging technologies: Worth the cost?

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

Cost will drive innovation

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

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

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

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

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

–Heidi Splete contributed to this article.

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

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

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

Patients May Overuse Medication for Years

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

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

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

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

Start With Patient Education

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

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

Do Preventive Therapies Work?

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

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

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

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

Detoxification

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

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

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

One Center’s Experience

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

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

—Jake Remaly

Suggested Reading

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

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

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

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

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

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

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

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

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

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

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

Patients May Overuse Medication for Years

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

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

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

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

Start With Patient Education

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

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

Do Preventive Therapies Work?

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

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

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

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

Detoxification

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

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

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

One Center’s Experience

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

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

—Jake Remaly

Suggested Reading

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

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

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

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

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

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

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

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

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

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

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

Patients May Overuse Medication for Years

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

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

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

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

Start With Patient Education

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

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

Do Preventive Therapies Work?

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

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

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

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

Detoxification

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

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

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

One Center’s Experience

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

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

—Jake Remaly

Suggested Reading

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

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

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

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

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

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

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

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

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

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

[email protected]

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

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

[email protected]

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

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

[email protected]

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

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

[email protected]

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

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

[email protected]

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

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

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

—Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

—Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

OJAI, CA—Soldiers with posttraumatic headaches are “complicated patients,” said Alan G. Finkel, MD, Director of the Carolina Headache Institute in Chapel Hill, North Carolina. No drugs are approved for the treatment of posttraumatic complications, and persistent posttraumatic headaches may interfere with return to military service.

Characteristics of posttraumatic headaches—such as whether they are continuous, nummular, or holocephalic—may provide prognostic clues and suggest possible therapies, Dr. Finkel said at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific. In addition, neurologists can address sleep, mood, and concussion symptoms when managing patients with posttraumatic headache.

Occupational Outcomes

Posttraumatic headaches most commonly are classified as migraine. Other classifications include tension-type headache and trigeminal autonomic cephalalgia. A patient may report multiple types of headache. Dr. Finkel and his research colleagues hypothesized that among patients with posttraumatic headache, the headache diagnosis may not be sufficient to predict occupational outcomes and that other headache characteristics might be more important.

To assess associations between headache characteristics and the outcome of leaving military service for medical reasons, Dr. Finkel and colleagues analyzed data from a retrospective cohort study. The cohort included 95 patients who were referred for headache evaluation at the Brain Injury Center at Womack Army Medical Center, Fort Bragg, North Carolina, between August 2008 and December 2009. The study was published online ahead of print February 27 in Headache.

About 14% of the patients had a history of headache, and about 40% had a prior history of concussion. The most common injury cited was blast injury (53.7%).

People were able to report as many as three headaches (ie, one continuous and two noncontinuous). The 95 patients reported 166 headaches. About 75% of the patients reported a continuous headache. Approximately 72% of patients reported a headache of a migraine type. The most clinically important headache was migraine for 61% of patients, tension-type headache for 4%, and trigeminal autonomic cephalalgias, including hemicrania continua, for 24%.

“The presence of a continuous headache was very likely to predict leaving service, and the headache diagnosis or the presence of a migraine diagnosis did not,” Dr. Finkel said.

Patients with continuous headache were approximately four times more likely to leave military service, compared with patients without continuous headache. Prior history of regular headache also appeared to predict the probability of discharge. Among patients with prior history of headache, continuous holocephalic headache, as well as the tendency to medicate and stay active with the most clinically important headache (as opposed to lying down or continuing activities without medication), also increased the likelihood of severance.

The study’s limitations included its retrospective design, the possibility of recall bias, and the lack of controls, Dr. Finkel noted.

Assessment Tools

When evaluating patients, instruments such as the Neurobehavioral Symptom Inventory and concussion checklists can be useful. “Get some tested baselines that you can then compare longitudinally,” he said.

The Balance Error Scoring System and the King–Devick test can assess concussion symptoms. “While you are making an assessment for persistent posttraumatic headache, make some comments in your chart about … whether or not they have concussive symptoms,” Dr. Finkel said. Neurologists also can assess problems with emotions and mood, which may be treatable. A combination of dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of emotional incontinence, which is associated with traumatic brain injury. Dr. Finkel uses the Pain Catastrophizing Scale and Posttraumatic Stress Disorder (PTSD) Checklist to evaluate pain-related anxiety. Neurologists also can ask patients about sleep, which may play an important role in patients’ recovery.

Treatment Options

In a clinic-based sample of 100 soldiers with chronic posttraumatic headache after mild head trauma, topiramate appeared to be an effective prophylactic.

Investigators plan to conduct a placebo-controlled trial of prazosin in patients with chronic postconcussive headache. Prazosin, an alpha one antagonist, may be prescribed to improve sleep and reduce nightmares. It may be a treatment option if a patient with chronic headache is hypervigilant and has insomnia, said Dr. Finkel. When prescribing prazosin, it is important to tell patients about the risk of fainting on the first night after taking the drug.

Defense Recommendation

The Department of Defense in February 2016 published a clinical recommendation for the primary care management of headache following concussion or mild traumatic brain injury. The recommendation describes red flags, establishes four categories into which symptoms might fall (ie, migraine, tension-type, cervicogenic, and neuropathic), and provides treatment guidance for each headache category.

If therapy alleviates holocephalic headaches, but focal pain persists, neurologists can try injecting onabotulinum toxin to treat the focal pain, Dr. Finkel said. In a case series of 64 patients with concussion-related headaches who were treated with onabotulinum toxin, 64% reported feeling better. The presence of PTSD did not appear to affect treatment outcomes, Dr. Finkel said.

Exercise and Expectation

Cardinal symptoms of concussion, including headache and PTSD, can improve with exercise, Dr. Finkel said. Evaluating patients on a treadmill can determine whether postconcussive symptoms recur at elevated heart rates. Patients can progressively increase the intensity of exercise until they are ready to resume activity.

When posttraumatic headache persists, neurologists should consider patients’ expectations. Research suggests that the language used to convey a diagnosis (eg, mild head injury, mild traumatic brain injury, or concussion) can affect what symptoms people anticipate. And patients’ perceptions of the illness may play a role in the persistence of postconcussion symptoms. Telling patients that they have a traumatic brain injury or expressing uncertainty about the diagnosis or prognosis is doing them a disservice, he said. “Tell them they are going to get better,” Dr. Finkel said.

—Jake Remaly

Suggested Reading

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932-944.

Finkel AG, Ivins BJ, Yerry JA, et al. Which matters more? A retrospective cohort study of headache characteristics and diagnosis type in soldiers with mTBI/concussion. Headache. 2017 Feb 27 [Epub ahead of print].

Finkel AG, Yerry JA, Klaric JS, et al. Headache in military service members with a history of mild traumatic brain injury: A cohort study of diagnosis and classification. Cephalalgia. 2016 May 20 [Epub ahead of print].

Whittaker R, Kemp S, House A. Illness perceptions and outcome in mild head injury: a longitudinal study. J Neurol Neurosurg Psychiatry. 2007;78(6):644-646.

Yerry JA, Kuehn D, Finkel AG. Onabotulinum toxin A for the treatment of headache in service members with a history of mild traumatic brain injury: a cohort study. Headache. 2015;55(3):395-406.

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

—Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

—Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.

HOUSTON—Although dual antiplatelet therapy provides a greater reduction in the risk of recurrent stroke than does antiplatelet monotherapy, adding a third agent may not increase the benefit, according to research presented at the International Stroke Conference 2017. Administering three antiplatelet agents does, however, increase the risk of bleeding, compared with dual antiplatelet therapy.

In 2012 and 2013, literature reviews suggested that the risk of recurrent stroke was reduced among patients who received two antiplatelet agents, compared with patients who received a single antiplatelet agent. These analyses prompted the question of whether triple antiplatelet therapy would provide a further risk reduction.

To examine this question, Philip Bath, MD, Chair of the Division of Clinical Neuroscience at the University of Nottingham, United Kingdom, and colleagues designed the Triple Antiplatelets for Reducing Dependency After Ischemic Stroke (TARDIS) trial. The researchers randomized patients with acute ischemic stroke or transient ischemic attack (TIA) to intensive therapy (ie, triple antiplatelet therapy) or standard of care (ie, dual antiplatelet therapy) for one month. After 30 days, all patients received standard of care. The study’s primary outcome was recurrent stroke or TIA at 90 days. Eligible patients entered the study within 48 hours of their index event, and patients with any level of stroke severity were accepted.

The investigators administered aspirin, clopidogrel, and dipyridamole to participants at standard doses. At the beginning of the trial, UK guidelines recommended the combination of aspirin and dipyridamole as first-line treatment for prevention of recurrent stroke. In 2010, the National Institute for Health and Care Excellence changed the guideline to recommend clopidogrel alone as first-line treatment. Dr. Bath and colleagues changed the treatment given to their standard-of-care group accordingly.

The researchers intended to enroll 4,100 participants, but ended the trial early on the recommendation of the data-monitoring committee. In all, 3,096 patients were enrolled. Their average age was 69. Approximately 63% of the population was male. The average time of stroke or TIA onset was 29 hours before enrollment. About one-third of patients had been taking antiplatelet therapy at baseline.

Dr. Bath and colleagues found no difference in the rate of recurrent stroke or TIA between treatment groups. Subgroup analysis found that people with an NIH Stroke Scale (NIHSS) score of 3 or lower at baseline tended to benefit from intensive therapy. Standard of care, however, tended to be superior for patients with an NIHSS score greater than 3. In addition, intensive therapy tended to be superior to the combination of aspirin and dipyridamole, but inferior to clopidogrel. Intensive therapy also was associated with significantly more bleeding and more severe bleeding.

—Erik Greb

Suggested Reading

Geeganage CM, Diener HC, Algra A, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012;43(4):1058-1066.

TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). Int J Stroke. 2015;10(7):1159-1165.

Wong KS, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013;128(15):1656-1666.

A vaccine against respiratory syncytial virus (RSV) is entering a phase 1 safety and tolerability trial. The vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is badly needed, according to Anthony Fauci, MD, director of NIAID. Although common and causing usually mild symptoms RSV infection also can lead to severe lower respiratory tract diseases, such as pneumonia and bronchiolitis in infants, children, the elderly, and immune-compromised patients. Globally, RSV infections cause upwards of 250,000 deaths each year. “RSV is underappreciated as a major cause of illness and death,” Fauci said.  

The vaccine (DS-Cav1) will fill a void. Currently no vaccine is available to prevent RSV infection, and no drug is available to treat it. The monoclonal antibody palivizumab is approved for preventing lower respiratory tract disease caused by RSV in high-risk children, but is not approved for use in the general population.

The study, VRC 317, will enroll healthy adults aged 18 to 50. Participants will be assigned randomly to receive 2 injections 12 weeks apart with the investigational vaccine or the investigational vaccine with alum, a compound commonly added to vaccines to enhance the immune response.

Participants also will be randomly assigned to receive 1 of 3 doses (50, 150, or 500 μg) at both time points. To start, 5 people will receive the 50-µg dose. If they experience no serious adverse reactions attributable to the vaccine the other participants will be vaccinated with the higher doses.

The participants will return for 12 clinic visits over 44 weeks  when researchers will conduct physical exams, collect blood samples, and test mucous samples to measure the immune response.

DS-Cav1 is the result of “years of research” at the Vaccine Research Center, the NIH says. Traditionally a vaccine is derived from a weakened or inactivated whole virus. By contrast, DS-Cav1 is a single, structurally engineered protein from the surface of RSV. Co-lead investigator Barney Graham, MD, PhD, deputy VRC director, says, “This work represents how new biological insights from basic research can lead to candidate vaccines for diseases of public health importance.”

A vaccine against respiratory syncytial virus (RSV) is entering a phase 1 safety and tolerability trial. The vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is badly needed, according to Anthony Fauci, MD, director of NIAID. Although common and causing usually mild symptoms RSV infection also can lead to severe lower respiratory tract diseases, such as pneumonia and bronchiolitis in infants, children, the elderly, and immune-compromised patients. Globally, RSV infections cause upwards of 250,000 deaths each year. “RSV is underappreciated as a major cause of illness and death,” Fauci said.  

The vaccine (DS-Cav1) will fill a void. Currently no vaccine is available to prevent RSV infection, and no drug is available to treat it. The monoclonal antibody palivizumab is approved for preventing lower respiratory tract disease caused by RSV in high-risk children, but is not approved for use in the general population.

The study, VRC 317, will enroll healthy adults aged 18 to 50. Participants will be assigned randomly to receive 2 injections 12 weeks apart with the investigational vaccine or the investigational vaccine with alum, a compound commonly added to vaccines to enhance the immune response.

Participants also will be randomly assigned to receive 1 of 3 doses (50, 150, or 500 μg) at both time points. To start, 5 people will receive the 50-µg dose. If they experience no serious adverse reactions attributable to the vaccine the other participants will be vaccinated with the higher doses.

The participants will return for 12 clinic visits over 44 weeks  when researchers will conduct physical exams, collect blood samples, and test mucous samples to measure the immune response.

DS-Cav1 is the result of “years of research” at the Vaccine Research Center, the NIH says. Traditionally a vaccine is derived from a weakened or inactivated whole virus. By contrast, DS-Cav1 is a single, structurally engineered protein from the surface of RSV. Co-lead investigator Barney Graham, MD, PhD, deputy VRC director, says, “This work represents how new biological insights from basic research can lead to candidate vaccines for diseases of public health importance.”

A vaccine against respiratory syncytial virus (RSV) is entering a phase 1 safety and tolerability trial. The vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is badly needed, according to Anthony Fauci, MD, director of NIAID. Although common and causing usually mild symptoms RSV infection also can lead to severe lower respiratory tract diseases, such as pneumonia and bronchiolitis in infants, children, the elderly, and immune-compromised patients. Globally, RSV infections cause upwards of 250,000 deaths each year. “RSV is underappreciated as a major cause of illness and death,” Fauci said.  

The vaccine (DS-Cav1) will fill a void. Currently no vaccine is available to prevent RSV infection, and no drug is available to treat it. The monoclonal antibody palivizumab is approved for preventing lower respiratory tract disease caused by RSV in high-risk children, but is not approved for use in the general population.

The study, VRC 317, will enroll healthy adults aged 18 to 50. Participants will be assigned randomly to receive 2 injections 12 weeks apart with the investigational vaccine or the investigational vaccine with alum, a compound commonly added to vaccines to enhance the immune response.

Participants also will be randomly assigned to receive 1 of 3 doses (50, 150, or 500 μg) at both time points. To start, 5 people will receive the 50-µg dose. If they experience no serious adverse reactions attributable to the vaccine the other participants will be vaccinated with the higher doses.

The participants will return for 12 clinic visits over 44 weeks  when researchers will conduct physical exams, collect blood samples, and test mucous samples to measure the immune response.

DS-Cav1 is the result of “years of research” at the Vaccine Research Center, the NIH says. Traditionally a vaccine is derived from a weakened or inactivated whole virus. By contrast, DS-Cav1 is a single, structurally engineered protein from the surface of RSV. Co-lead investigator Barney Graham, MD, PhD, deputy VRC director, says, “This work represents how new biological insights from basic research can lead to candidate vaccines for diseases of public health importance.”

Image by Spencer Phillips

Whole-exome sequencing (WES) may routinely miss genetic variations associated with leukemia and other diseases, according to research published in Scientific Reports.

The study revealed 832 genes that have low coverage across multiple WES platforms.

These genes are associated with leukemia, psoriasis, heart failure, and other diseases, and they may be missed by researchers using WES to study these diseases.

“Although it was known that coverage—the average number of times a given piece of DNA is read during sequencing—could be uneven in whole-exome sequencing, our new methods are the first to really quantify this,” said study author Santhosh Girirajan, MBBS, PhD, of The Pennsylvania State University, University Park.

“Adequate coverage—often as many as 70 or more reads for each piece of DNA—increases our confidence that the sequence is accurate, and, without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease.”

“In our study, we found 832 genes that have systematically low coverage across 3 different sequencing platforms, meaning that these genes would be missed in disease studies.”

The researchers said low-coverage regions may result from limited precision in WES technologies due to certain genomic features.

Highly repetitive stretches of DNA can prevent the sequencer from reading the DNA properly. The study showed that at least 60% of low-coverage genes occur near DNA repeats.

“One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes,” Dr Girirajan said. “Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome.”

“However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.”

Image by Spencer Phillips

Whole-exome sequencing (WES) may routinely miss genetic variations associated with leukemia and other diseases, according to research published in Scientific Reports.

The study revealed 832 genes that have low coverage across multiple WES platforms.

These genes are associated with leukemia, psoriasis, heart failure, and other diseases, and they may be missed by researchers using WES to study these diseases.

“Although it was known that coverage—the average number of times a given piece of DNA is read during sequencing—could be uneven in whole-exome sequencing, our new methods are the first to really quantify this,” said study author Santhosh Girirajan, MBBS, PhD, of The Pennsylvania State University, University Park.

“Adequate coverage—often as many as 70 or more reads for each piece of DNA—increases our confidence that the sequence is accurate, and, without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease.”

“In our study, we found 832 genes that have systematically low coverage across 3 different sequencing platforms, meaning that these genes would be missed in disease studies.”

The researchers said low-coverage regions may result from limited precision in WES technologies due to certain genomic features.

Highly repetitive stretches of DNA can prevent the sequencer from reading the DNA properly. The study showed that at least 60% of low-coverage genes occur near DNA repeats.

“One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes,” Dr Girirajan said. “Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome.”

“However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.”

Image by Spencer Phillips

Whole-exome sequencing (WES) may routinely miss genetic variations associated with leukemia and other diseases, according to research published in Scientific Reports.

The study revealed 832 genes that have low coverage across multiple WES platforms.

These genes are associated with leukemia, psoriasis, heart failure, and other diseases, and they may be missed by researchers using WES to study these diseases.

“Although it was known that coverage—the average number of times a given piece of DNA is read during sequencing—could be uneven in whole-exome sequencing, our new methods are the first to really quantify this,” said study author Santhosh Girirajan, MBBS, PhD, of The Pennsylvania State University, University Park.

“Adequate coverage—often as many as 70 or more reads for each piece of DNA—increases our confidence that the sequence is accurate, and, without it, it is nearly impossible to make confident predictions about the relationship between a mutation in a gene and a disease.”

“In our study, we found 832 genes that have systematically low coverage across 3 different sequencing platforms, meaning that these genes would be missed in disease studies.”

The researchers said low-coverage regions may result from limited precision in WES technologies due to certain genomic features.

Highly repetitive stretches of DNA can prevent the sequencer from reading the DNA properly. The study showed that at least 60% of low-coverage genes occur near DNA repeats.

“One solution to this problem is for researchers to use whole-genome sequencing, which examines all base pairs of DNA instead of just the regions that contain genes,” Dr Girirajan said. “Our study found that whole-genome data had significantly fewer low-coverage genes than whole-exome data, and its coverage is more uniformly distributed across all parts of the genome.”

“However, the costs of whole-exome sequencing are still significantly lower than whole-genome sequencing. Until the costs of whole-genome sequencing is no longer a barrier, human genetics researchers should be aware of these limitations in whole-exome sequencing technologies.”