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Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows.

Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep.

LPETTET/Getty Images

A common problem

Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening.

For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance.

In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol may result in tolerance to the sleep-enhancing effects of cannabis.

With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain.

“People are self-reporting that they’re using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn’t mean that it will hold up in research,” Dr. Sznitman said.

The study included 128 individuals (mean age, 61±6 years; 51% females) with chronic neuropathic pain: 66 were medical cannabis users and 62 were not.

Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance.

In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use.
 

Frequent use, more sleep problems?

On average, medical cannabis users were 3 years younger than their nonusing counterparts (mean age, 60±6 vs. 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable.

Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%).

Results showed that, of the total sample, 24.1% reported always waking up early and not falling back to sleep, 20.2% reported always having difficulty falling asleep, and 27.2% reported always waking up during the night.

After adjusting for patient age, sex, pain level, and use of sleep medications and antidepressants, medical cannabis use was associated with fewer problems with waking up at night, compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep, Dr. Sznitman and associates reported.

The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems, they said.

Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep.

Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis also maybsuffer pain or other comorbidities, which, in turn, may be linked to more sleep problems.

Either way, Dr. Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep.

“If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients,” she said.
 

Early days

Commenting on the findings in an interview, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research.

“I think the results make sense with respect to the data I’ve collected and from what I’ve seen,” said Dr. Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.

“We typically only want to use sleep medications for short periods of time,” he continued. “When you think about recommended prescribing practices for any hypnotic medication, it’s usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep,” Dr. Vandrey said.

Nevertheless, he urged caution when interpreting the results.

“I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep,” he said. “But we need more detailed evaluations, as the trial wasn’t testing a defined product, specific dose, or dose regimen.

“In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems.”

Dr. Sznitman agreed that the research is still in its very early stages.

“We’re still far from saying we have the evidence to support the use of medical cannabis for sleep,” she said. “For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting.”

The study was funded by the University of Haifa and Rambam Hospital in Israel, and by the Evelyn Lipper Foundation. Dr. Sznitman and Dr. Vandrey have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.
 

Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows.

Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep.

LPETTET/Getty Images

A common problem

Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening.

For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance.

In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol may result in tolerance to the sleep-enhancing effects of cannabis.

With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain.

“People are self-reporting that they’re using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn’t mean that it will hold up in research,” Dr. Sznitman said.

The study included 128 individuals (mean age, 61±6 years; 51% females) with chronic neuropathic pain: 66 were medical cannabis users and 62 were not.

Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance.

In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use.
 

Frequent use, more sleep problems?

On average, medical cannabis users were 3 years younger than their nonusing counterparts (mean age, 60±6 vs. 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable.

Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%).

Results showed that, of the total sample, 24.1% reported always waking up early and not falling back to sleep, 20.2% reported always having difficulty falling asleep, and 27.2% reported always waking up during the night.

After adjusting for patient age, sex, pain level, and use of sleep medications and antidepressants, medical cannabis use was associated with fewer problems with waking up at night, compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep, Dr. Sznitman and associates reported.

The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems, they said.

Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep.

Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis also maybsuffer pain or other comorbidities, which, in turn, may be linked to more sleep problems.

Either way, Dr. Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep.

“If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients,” she said.
 

Early days

Commenting on the findings in an interview, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research.

“I think the results make sense with respect to the data I’ve collected and from what I’ve seen,” said Dr. Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.

“We typically only want to use sleep medications for short periods of time,” he continued. “When you think about recommended prescribing practices for any hypnotic medication, it’s usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep,” Dr. Vandrey said.

Nevertheless, he urged caution when interpreting the results.

“I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep,” he said. “But we need more detailed evaluations, as the trial wasn’t testing a defined product, specific dose, or dose regimen.

“In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems.”

Dr. Sznitman agreed that the research is still in its very early stages.

“We’re still far from saying we have the evidence to support the use of medical cannabis for sleep,” she said. “For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting.”

The study was funded by the University of Haifa and Rambam Hospital in Israel, and by the Evelyn Lipper Foundation. Dr. Sznitman and Dr. Vandrey have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.
 

Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows.

Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep.

LPETTET/Getty Images

A common problem

Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening.

For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance.

In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol may result in tolerance to the sleep-enhancing effects of cannabis.

With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain.

“People are self-reporting that they’re using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn’t mean that it will hold up in research,” Dr. Sznitman said.

The study included 128 individuals (mean age, 61±6 years; 51% females) with chronic neuropathic pain: 66 were medical cannabis users and 62 were not.

Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance.

In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use.
 

Frequent use, more sleep problems?

On average, medical cannabis users were 3 years younger than their nonusing counterparts (mean age, 60±6 vs. 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable.

Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%).

Results showed that, of the total sample, 24.1% reported always waking up early and not falling back to sleep, 20.2% reported always having difficulty falling asleep, and 27.2% reported always waking up during the night.

After adjusting for patient age, sex, pain level, and use of sleep medications and antidepressants, medical cannabis use was associated with fewer problems with waking up at night, compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep, Dr. Sznitman and associates reported.

The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems, they said.

Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep.

Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis also maybsuffer pain or other comorbidities, which, in turn, may be linked to more sleep problems.

Either way, Dr. Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep.

“If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients,” she said.
 

Early days

Commenting on the findings in an interview, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research.

“I think the results make sense with respect to the data I’ve collected and from what I’ve seen,” said Dr. Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.

“We typically only want to use sleep medications for short periods of time,” he continued. “When you think about recommended prescribing practices for any hypnotic medication, it’s usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep,” Dr. Vandrey said.

Nevertheless, he urged caution when interpreting the results.

“I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep,” he said. “But we need more detailed evaluations, as the trial wasn’t testing a defined product, specific dose, or dose regimen.

“In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems.”

Dr. Sznitman agreed that the research is still in its very early stages.

“We’re still far from saying we have the evidence to support the use of medical cannabis for sleep,” she said. “For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting.”

The study was funded by the University of Haifa and Rambam Hospital in Israel, and by the Evelyn Lipper Foundation. Dr. Sznitman and Dr. Vandrey have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.
 

As the Wuhan coronavirus story unfolds, the most important thing for clinicians in the United States to do is ask patients who appear to have the flu if they, or someone they have been in contact with, recently returned from China, according to infectious disease experts.

China News Service/CC BY 3.0

“We are asking that of everyone with fever and respiratory symptoms who comes to our clinics, hospital, or emergency room. It’s a powerful screening tool,” said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

In addition to fever, common signs of infection include cough, shortness of breath, and breathing difficulties. Some patients have had diarrhea, vomiting, and other gastrointestinal symptoms. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and death. The incubation period appears to be up to 2 weeks, according to the World Health Organization (WHO).

If patients exhibit symptoms and either they or a close contact has returned from China recently, take standard airborne precautions and send specimens – a serum sample, oral and nasal pharyngeal swabs, and lower respiratory tract specimens if available – to the local health department, which will forward them to the Centers for Disease Control and Prevention (CDC) for testing. Turnaround time is 24-48 hours.

Plan and rehearse

The first step to prepare is to use the CDC’s Interim Guidance for Healthcare Professionals to make a written plan specific to your practice to respond to a potential case. The plan must include notifying the local health department, the CDC liaison for testing, and tracking down patient contacts.

“It’s not good enough to just download CDC’s guidance; use it to make your own local plan and know what to do 24/7,” said Daniel Lucey, MD, an infectious disease expert at Georgetown University Medical Center, Washington, D.C.

“Know who is on call at the health department on weekends and nights,” he said. Know where the patient is going to be isolated; figure out what to do if there’s more than one, and tests come back positive. Have masks on hand, and rehearse the response. “Make a coronavirus team, and absolutely have the nurses involved,” as well as other providers who may come into contact with a case, he added.

Fatality rates

The focus right now is China. The outbreak has spread beyond Wuhan to other parts of the country, and there’s evidence of fourth-generation spread.

SARS: Lessons learned

In general, the world is much better equipped for coronavirus outbreaks than when SARS, in particular, emerged in 2003.

aotto@mdedge.com

This article was updated with new case numbers on 1/26/20.

As the Wuhan coronavirus story unfolds, the most important thing for clinicians in the United States to do is ask patients who appear to have the flu if they, or someone they have been in contact with, recently returned from China, according to infectious disease experts.

China News Service/CC BY 3.0

“We are asking that of everyone with fever and respiratory symptoms who comes to our clinics, hospital, or emergency room. It’s a powerful screening tool,” said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

In addition to fever, common signs of infection include cough, shortness of breath, and breathing difficulties. Some patients have had diarrhea, vomiting, and other gastrointestinal symptoms. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and death. The incubation period appears to be up to 2 weeks, according to the World Health Organization (WHO).

If patients exhibit symptoms and either they or a close contact has returned from China recently, take standard airborne precautions and send specimens – a serum sample, oral and nasal pharyngeal swabs, and lower respiratory tract specimens if available – to the local health department, which will forward them to the Centers for Disease Control and Prevention (CDC) for testing. Turnaround time is 24-48 hours.

Plan and rehearse

The first step to prepare is to use the CDC’s Interim Guidance for Healthcare Professionals to make a written plan specific to your practice to respond to a potential case. The plan must include notifying the local health department, the CDC liaison for testing, and tracking down patient contacts.

“It’s not good enough to just download CDC’s guidance; use it to make your own local plan and know what to do 24/7,” said Daniel Lucey, MD, an infectious disease expert at Georgetown University Medical Center, Washington, D.C.

“Know who is on call at the health department on weekends and nights,” he said. Know where the patient is going to be isolated; figure out what to do if there’s more than one, and tests come back positive. Have masks on hand, and rehearse the response. “Make a coronavirus team, and absolutely have the nurses involved,” as well as other providers who may come into contact with a case, he added.

Fatality rates

The focus right now is China. The outbreak has spread beyond Wuhan to other parts of the country, and there’s evidence of fourth-generation spread.

SARS: Lessons learned

In general, the world is much better equipped for coronavirus outbreaks than when SARS, in particular, emerged in 2003.

aotto@mdedge.com

This article was updated with new case numbers on 1/26/20.

As the Wuhan coronavirus story unfolds, the most important thing for clinicians in the United States to do is ask patients who appear to have the flu if they, or someone they have been in contact with, recently returned from China, according to infectious disease experts.

China News Service/CC BY 3.0

“We are asking that of everyone with fever and respiratory symptoms who comes to our clinics, hospital, or emergency room. It’s a powerful screening tool,” said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

In addition to fever, common signs of infection include cough, shortness of breath, and breathing difficulties. Some patients have had diarrhea, vomiting, and other gastrointestinal symptoms. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and death. The incubation period appears to be up to 2 weeks, according to the World Health Organization (WHO).

If patients exhibit symptoms and either they or a close contact has returned from China recently, take standard airborne precautions and send specimens – a serum sample, oral and nasal pharyngeal swabs, and lower respiratory tract specimens if available – to the local health department, which will forward them to the Centers for Disease Control and Prevention (CDC) for testing. Turnaround time is 24-48 hours.

Plan and rehearse

The first step to prepare is to use the CDC’s Interim Guidance for Healthcare Professionals to make a written plan specific to your practice to respond to a potential case. The plan must include notifying the local health department, the CDC liaison for testing, and tracking down patient contacts.

“It’s not good enough to just download CDC’s guidance; use it to make your own local plan and know what to do 24/7,” said Daniel Lucey, MD, an infectious disease expert at Georgetown University Medical Center, Washington, D.C.

“Know who is on call at the health department on weekends and nights,” he said. Know where the patient is going to be isolated; figure out what to do if there’s more than one, and tests come back positive. Have masks on hand, and rehearse the response. “Make a coronavirus team, and absolutely have the nurses involved,” as well as other providers who may come into contact with a case, he added.

Fatality rates

The focus right now is China. The outbreak has spread beyond Wuhan to other parts of the country, and there’s evidence of fourth-generation spread.

SARS: Lessons learned

In general, the world is much better equipped for coronavirus outbreaks than when SARS, in particular, emerged in 2003.

aotto@mdedge.com

This article was updated with new case numbers on 1/26/20.

The Food and Drug Administration has issued a warning that certain GE Healthcare Clinical Information Central Stations and Telemetry Servers have cybersecurity vulnerabilities that may introduce risk to monitored patients.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A security firm identified several vulnerabilities in the GE devices that allow attackers to remotely take control of the medical device, silence alarms, generate false alarms, and interfere with alarms of patient monitors connected to these devices, according to an “Urgent Medical Device Correction” letter issued by GE Healthcare in November 2019.

The affected devices are the ApexPro Telemetry Server and CARESCAPE Telemetry Server, the CARESCAPE Central Station (CSCS) version 1, and the CIC Pro Clinical Information Center Central Station version 1. These devices are used in health care facilities for displaying information, such as the patient’s physiological parameters, and for monitoring patient status from a central location in a facility.

No adverse events related to the vulnerabilities have been reported to the FDA. Health care facility staff should update their devices when GE Healthcare issues a software patch that addresses the vulnerability, separate the network connecting patient monitors using affected devices from the rest of the hospital, and use firewalls and other means to minimize the risk of remote or local network attacks.

“The FDA takes reports of cybersecurity vulnerabilities in medical devices seriously and will continue to work with GE Healthcare as the firm develops software patches to correct these vulnerabilities as soon as possible. The FDA will continue to assess new information concerning the vulnerabilities and will keep the public informed if significant new information becomes available,” the FDA said in the Safety Communication.

lfranki@mdedge.com

The Food and Drug Administration has issued a warning that certain GE Healthcare Clinical Information Central Stations and Telemetry Servers have cybersecurity vulnerabilities that may introduce risk to monitored patients.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A security firm identified several vulnerabilities in the GE devices that allow attackers to remotely take control of the medical device, silence alarms, generate false alarms, and interfere with alarms of patient monitors connected to these devices, according to an “Urgent Medical Device Correction” letter issued by GE Healthcare in November 2019.

The affected devices are the ApexPro Telemetry Server and CARESCAPE Telemetry Server, the CARESCAPE Central Station (CSCS) version 1, and the CIC Pro Clinical Information Center Central Station version 1. These devices are used in health care facilities for displaying information, such as the patient’s physiological parameters, and for monitoring patient status from a central location in a facility.

No adverse events related to the vulnerabilities have been reported to the FDA. Health care facility staff should update their devices when GE Healthcare issues a software patch that addresses the vulnerability, separate the network connecting patient monitors using affected devices from the rest of the hospital, and use firewalls and other means to minimize the risk of remote or local network attacks.

“The FDA takes reports of cybersecurity vulnerabilities in medical devices seriously and will continue to work with GE Healthcare as the firm develops software patches to correct these vulnerabilities as soon as possible. The FDA will continue to assess new information concerning the vulnerabilities and will keep the public informed if significant new information becomes available,” the FDA said in the Safety Communication.

lfranki@mdedge.com

The Food and Drug Administration has issued a warning that certain GE Healthcare Clinical Information Central Stations and Telemetry Servers have cybersecurity vulnerabilities that may introduce risk to monitored patients.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A security firm identified several vulnerabilities in the GE devices that allow attackers to remotely take control of the medical device, silence alarms, generate false alarms, and interfere with alarms of patient monitors connected to these devices, according to an “Urgent Medical Device Correction” letter issued by GE Healthcare in November 2019.

The affected devices are the ApexPro Telemetry Server and CARESCAPE Telemetry Server, the CARESCAPE Central Station (CSCS) version 1, and the CIC Pro Clinical Information Center Central Station version 1. These devices are used in health care facilities for displaying information, such as the patient’s physiological parameters, and for monitoring patient status from a central location in a facility.

No adverse events related to the vulnerabilities have been reported to the FDA. Health care facility staff should update their devices when GE Healthcare issues a software patch that addresses the vulnerability, separate the network connecting patient monitors using affected devices from the rest of the hospital, and use firewalls and other means to minimize the risk of remote or local network attacks.

“The FDA takes reports of cybersecurity vulnerabilities in medical devices seriously and will continue to work with GE Healthcare as the firm develops software patches to correct these vulnerabilities as soon as possible. The FDA will continue to assess new information concerning the vulnerabilities and will keep the public informed if significant new information becomes available,” the FDA said in the Safety Communication.

lfranki@mdedge.com

In 1982, I went to my first concert. It was Rush, on their “Signals” tour, and I loved it. In fact, I went back and saw them again about a year later. I bought a concert T-shirt at the first one. I still have it somewhere, though I am pretty sure it hasn’t fit me in years.

Weatherman90/Wikimedia Commons/CC BY 3.0

I loved their music before the concert, enjoyed it even more afterwards, and still do. Their albums are all on my computer and phone, and part of the daily soundtrack of my life when working at my desk, driving, and walking (I’m trying to fit back in the shirt).

On Jan. 7, 2020, Neil Peart, the trio’s remarkably gifted drummer, died of a neurologic disease.

According to the news, he had a glioblastoma multiforme, a tumor terrifying for its aggressiveness, difficulty of treatment, and lack of preventable risk factors.

The cost of neurologic disease is terrible. Glioblastoma multiforme, unfortunately, is far from rare, nor is it the only one. In recent times, entertainers afflicted with neurologic disease have included Neil Diamond, Linda Ronstadt, Peter Falk, Glen Campbell, Charlton Heston, Gene Siskel, Michael J. Fox, Stephen Hillenburg, Teri Garr, Annette Funicello, Robin Williams, Dudley Moore, and most recently Ozzy Osbourne.

That’s a pretty short list, too, far from all-encompassing. The majority of people with these disorders won’t be in the news. Their everyday struggles, stories, and losses are known only to family, friends, and the medical team doing its best to help.

Medical technology advances every year. In the 22 years since I began practicing, we’ve made remarkable strides in some areas – multiple sclerosis, for example. But our work in so many other areas is nowhere close. The increasing knowledge as to the mechanisms and causes of Alzheimer’s disease have, to date, failed to translate into treatment success.

That’s not to say we should give up. Far from it. Our species has gotten where we are by always wanting to get over the next hill. Initial failures will always outnumber successes. But when you’re a doctor dealing with the very real human cost of neurologic disease, that’s not much consolation. And it’s far less so for the patients and families affected who come to us for help.

We use terms like “burden” or “cost” to discuss the financial aspects of illness, but they often don’t seem adequate to describe the real effects. The emotional damages. The gifted musicians and loved family members lost. Family members struggling with the difficult role of being care givers.

Neurologic disease doesn’t discriminate against anyone, regardless of age, fame, or talent. I’ll stay here and do my best for all of them who come to me. I’m certainly not on the front line of research. That’s incredibly important, but I’ll leave it to others. My work is where the patients are every day.

Thank you for the music, Neil.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In 1982, I went to my first concert. It was Rush, on their “Signals” tour, and I loved it. In fact, I went back and saw them again about a year later. I bought a concert T-shirt at the first one. I still have it somewhere, though I am pretty sure it hasn’t fit me in years.

Weatherman90/Wikimedia Commons/CC BY 3.0

I loved their music before the concert, enjoyed it even more afterwards, and still do. Their albums are all on my computer and phone, and part of the daily soundtrack of my life when working at my desk, driving, and walking (I’m trying to fit back in the shirt).

On Jan. 7, 2020, Neil Peart, the trio’s remarkably gifted drummer, died of a neurologic disease.

According to the news, he had a glioblastoma multiforme, a tumor terrifying for its aggressiveness, difficulty of treatment, and lack of preventable risk factors.

The cost of neurologic disease is terrible. Glioblastoma multiforme, unfortunately, is far from rare, nor is it the only one. In recent times, entertainers afflicted with neurologic disease have included Neil Diamond, Linda Ronstadt, Peter Falk, Glen Campbell, Charlton Heston, Gene Siskel, Michael J. Fox, Stephen Hillenburg, Teri Garr, Annette Funicello, Robin Williams, Dudley Moore, and most recently Ozzy Osbourne.

That’s a pretty short list, too, far from all-encompassing. The majority of people with these disorders won’t be in the news. Their everyday struggles, stories, and losses are known only to family, friends, and the medical team doing its best to help.

Medical technology advances every year. In the 22 years since I began practicing, we’ve made remarkable strides in some areas – multiple sclerosis, for example. But our work in so many other areas is nowhere close. The increasing knowledge as to the mechanisms and causes of Alzheimer’s disease have, to date, failed to translate into treatment success.

That’s not to say we should give up. Far from it. Our species has gotten where we are by always wanting to get over the next hill. Initial failures will always outnumber successes. But when you’re a doctor dealing with the very real human cost of neurologic disease, that’s not much consolation. And it’s far less so for the patients and families affected who come to us for help.

We use terms like “burden” or “cost” to discuss the financial aspects of illness, but they often don’t seem adequate to describe the real effects. The emotional damages. The gifted musicians and loved family members lost. Family members struggling with the difficult role of being care givers.

Neurologic disease doesn’t discriminate against anyone, regardless of age, fame, or talent. I’ll stay here and do my best for all of them who come to me. I’m certainly not on the front line of research. That’s incredibly important, but I’ll leave it to others. My work is where the patients are every day.

Thank you for the music, Neil.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In 1982, I went to my first concert. It was Rush, on their “Signals” tour, and I loved it. In fact, I went back and saw them again about a year later. I bought a concert T-shirt at the first one. I still have it somewhere, though I am pretty sure it hasn’t fit me in years.

Weatherman90/Wikimedia Commons/CC BY 3.0

I loved their music before the concert, enjoyed it even more afterwards, and still do. Their albums are all on my computer and phone, and part of the daily soundtrack of my life when working at my desk, driving, and walking (I’m trying to fit back in the shirt).

On Jan. 7, 2020, Neil Peart, the trio’s remarkably gifted drummer, died of a neurologic disease.

According to the news, he had a glioblastoma multiforme, a tumor terrifying for its aggressiveness, difficulty of treatment, and lack of preventable risk factors.

The cost of neurologic disease is terrible. Glioblastoma multiforme, unfortunately, is far from rare, nor is it the only one. In recent times, entertainers afflicted with neurologic disease have included Neil Diamond, Linda Ronstadt, Peter Falk, Glen Campbell, Charlton Heston, Gene Siskel, Michael J. Fox, Stephen Hillenburg, Teri Garr, Annette Funicello, Robin Williams, Dudley Moore, and most recently Ozzy Osbourne.

That’s a pretty short list, too, far from all-encompassing. The majority of people with these disorders won’t be in the news. Their everyday struggles, stories, and losses are known only to family, friends, and the medical team doing its best to help.

Medical technology advances every year. In the 22 years since I began practicing, we’ve made remarkable strides in some areas – multiple sclerosis, for example. But our work in so many other areas is nowhere close. The increasing knowledge as to the mechanisms and causes of Alzheimer’s disease have, to date, failed to translate into treatment success.

That’s not to say we should give up. Far from it. Our species has gotten where we are by always wanting to get over the next hill. Initial failures will always outnumber successes. But when you’re a doctor dealing with the very real human cost of neurologic disease, that’s not much consolation. And it’s far less so for the patients and families affected who come to us for help.

We use terms like “burden” or “cost” to discuss the financial aspects of illness, but they often don’t seem adequate to describe the real effects. The emotional damages. The gifted musicians and loved family members lost. Family members struggling with the difficult role of being care givers.

Neurologic disease doesn’t discriminate against anyone, regardless of age, fame, or talent. I’ll stay here and do my best for all of them who come to me. I’m certainly not on the front line of research. That’s incredibly important, but I’ll leave it to others. My work is where the patients are every day.

Thank you for the music, Neil.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

LA JOLLA, CALIF. – Physicians and other medical professionals who routinely foster empathic connections with patients may be helping themselves steer clear of burnout.

That’s what iconic actor Alan Alda suggested during a media briefing at Scripps Research on Jan. 16, 2020.

Vidyard Video

“There’s a tremendous pressure on doctors now to have shorter and shorter visits with their patients,” said the 83-year-old Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016 for his work as a champion of science. “A lot of that time is taken up with recording on a computer, which can only put pressure on the doctor.”

Practicing empathy, he continued, “kind of opens people up to one another, which inspirits them.”

Mr. Alda appeared on the research campus to announce that Scripps Research will serve as the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at Stony Brook (N.Y.) University, a nonprofit organization that Mr. Alda helped found in 2009.

“This will be a center where people can come to get training in effective communication,” Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards, told an audience of scientists and medical professionals prior to the media briefing.

“It’s an experiential kind of training,” he explained. “We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that, when you get a diagnosis, your life is over,” said Mr. Alda, who played army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H.”

“Under the burden of that belief, some people won’t tell their family or workplace colleagues,” he said. “There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

dbrunk@mdedge.com

LA JOLLA, CALIF. – Physicians and other medical professionals who routinely foster empathic connections with patients may be helping themselves steer clear of burnout.

That’s what iconic actor Alan Alda suggested during a media briefing at Scripps Research on Jan. 16, 2020.

Vidyard Video

“There’s a tremendous pressure on doctors now to have shorter and shorter visits with their patients,” said the 83-year-old Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016 for his work as a champion of science. “A lot of that time is taken up with recording on a computer, which can only put pressure on the doctor.”

Practicing empathy, he continued, “kind of opens people up to one another, which inspirits them.”

Mr. Alda appeared on the research campus to announce that Scripps Research will serve as the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at Stony Brook (N.Y.) University, a nonprofit organization that Mr. Alda helped found in 2009.

“This will be a center where people can come to get training in effective communication,” Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards, told an audience of scientists and medical professionals prior to the media briefing.

“It’s an experiential kind of training,” he explained. “We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that, when you get a diagnosis, your life is over,” said Mr. Alda, who played army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H.”

“Under the burden of that belief, some people won’t tell their family or workplace colleagues,” he said. “There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

dbrunk@mdedge.com

LA JOLLA, CALIF. – Physicians and other medical professionals who routinely foster empathic connections with patients may be helping themselves steer clear of burnout.

That’s what iconic actor Alan Alda suggested during a media briefing at Scripps Research on Jan. 16, 2020.

Vidyard Video

“There’s a tremendous pressure on doctors now to have shorter and shorter visits with their patients,” said the 83-year-old Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016 for his work as a champion of science. “A lot of that time is taken up with recording on a computer, which can only put pressure on the doctor.”

Practicing empathy, he continued, “kind of opens people up to one another, which inspirits them.”

Mr. Alda appeared on the research campus to announce that Scripps Research will serve as the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at Stony Brook (N.Y.) University, a nonprofit organization that Mr. Alda helped found in 2009.

“This will be a center where people can come to get training in effective communication,” Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards, told an audience of scientists and medical professionals prior to the media briefing.

“It’s an experiential kind of training,” he explained. “We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that, when you get a diagnosis, your life is over,” said Mr. Alda, who played army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H.”

“Under the burden of that belief, some people won’t tell their family or workplace colleagues,” he said. “There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

dbrunk@mdedge.com

Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race, researchers reported Jan. 22 in Neurology.

“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
 

A subset of ERICH participants

To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.

Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.

The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).

The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.

“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”

Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
 

Vascular risks and oral anticoagulants

About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”

“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”

The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.

The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”

ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.

jremaly@mdedge.com

SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.

Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race, researchers reported Jan. 22 in Neurology.

“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
 

A subset of ERICH participants

To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.

Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.

The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).

The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.

“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”

Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
 

Vascular risks and oral anticoagulants

About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”

“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”

The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.

The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”

ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.

jremaly@mdedge.com

SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.

Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race, researchers reported Jan. 22 in Neurology.

“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
 

A subset of ERICH participants

To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.

Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.

The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).

The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.

“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”

Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
 

Vascular risks and oral anticoagulants

About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”

“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”

The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.

The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”

ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.

jremaly@mdedge.com

SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.

This column should arrive just in time. By now, you may have already failed some or all of your New Year’s resolutions. By this time in February, eighty percent of us will abort what we resolved to do this year. If this was you, it could be considered a catastrophic failure because not only is it a new year, it is a new decade. That’s right, the opportunity to fix the 10-year-imperfect you won’t come again until 2030!

marekuliasz/iStock/Getty Images

I’m among you. I intended to read fiction daily (starting with “The Great Gatsby,” not “Moby Dick” – I thought I would give myself a fighting chance, but alas ...), to workout at least 5 days every week (I tore my left triangular fibrocartilage complex, so there’s that), to write at least 500 words daily (I’m typing this one-handed: I’m lucky to get 500 letters a day). So I’m out.

If you resolved to do something this year, chances are it was to make a better you: a self-improvement goal such as losing weight, saving more money, or exercising more. According to a Marist Poll, these were the most popular resolutions for 2020. At the bottom of the most-likely-resolutions list were things like “worry less” or “be kinder to others.” These are important goals we’d agree, but we don’t deem them resolution-worthy. Why?

And why do we have New Year’s resolutions in the first place? When I looked into this further, I was surprised by some of the history I discovered.

As far back as the Babylonians, once a year, we’ve tried our best to get better. At the feast of Akitu, the Babylonian new year festival (about March on our modern calendar), people resolved to do a better job of paying debts and returning favors – spin had not been invented, and yoga hadn’t caught on in the Middle East yet. This fundamental desire to be a better human seems hardwired, and long before Bullet Journals we seem to have loved “fresh start” days on the calendar. Yet, we’re doomed to fail, over and over, at least for the last 5,000 or so attempts.

We know so much more now. Put your Nike Renue Fusion shoes next to your bed so you get up and run first thing. Set SMART goals. Sign up for automatic retirement contribution and for automatic, plant-based meal delivery from Blue Apron. (I’ve no conflict of interest in these products).

Good ideas all, but I’m suggesting a different approach: Resolve to do something else this year.

Rather than try the same things we’ve attempted, how about selecting something from the bottom of the Marist Poll list – such as resolving to be more humble. Admit when you don’t know something or don’t understand what’s being discussed. Recognize and acknowledge when you’ve screwed up. Or resolve to be more selfless. Add on someone else’s patient, an extra call without expecting a favor in return, or do what you can to help a curbside consult, even if there is no reward or even a small risk to you. Repay the debt you owe your friends, family, colleagues, staff, and patients.

These things are a little trickier to track, but you can find a way to keep yourself accountable. Add a box to your weekly planner that says “Be humble and kind” and check it off for the next 42 weeks. Good news, March 1 falls on a Sunday this year – let’s call it the feast of Akitu.

Happy New Year! And good luck!
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

This column should arrive just in time. By now, you may have already failed some or all of your New Year’s resolutions. By this time in February, eighty percent of us will abort what we resolved to do this year. If this was you, it could be considered a catastrophic failure because not only is it a new year, it is a new decade. That’s right, the opportunity to fix the 10-year-imperfect you won’t come again until 2030!

marekuliasz/iStock/Getty Images

I’m among you. I intended to read fiction daily (starting with “The Great Gatsby,” not “Moby Dick” – I thought I would give myself a fighting chance, but alas ...), to workout at least 5 days every week (I tore my left triangular fibrocartilage complex, so there’s that), to write at least 500 words daily (I’m typing this one-handed: I’m lucky to get 500 letters a day). So I’m out.

If you resolved to do something this year, chances are it was to make a better you: a self-improvement goal such as losing weight, saving more money, or exercising more. According to a Marist Poll, these were the most popular resolutions for 2020. At the bottom of the most-likely-resolutions list were things like “worry less” or “be kinder to others.” These are important goals we’d agree, but we don’t deem them resolution-worthy. Why?

And why do we have New Year’s resolutions in the first place? When I looked into this further, I was surprised by some of the history I discovered.

As far back as the Babylonians, once a year, we’ve tried our best to get better. At the feast of Akitu, the Babylonian new year festival (about March on our modern calendar), people resolved to do a better job of paying debts and returning favors – spin had not been invented, and yoga hadn’t caught on in the Middle East yet. This fundamental desire to be a better human seems hardwired, and long before Bullet Journals we seem to have loved “fresh start” days on the calendar. Yet, we’re doomed to fail, over and over, at least for the last 5,000 or so attempts.

We know so much more now. Put your Nike Renue Fusion shoes next to your bed so you get up and run first thing. Set SMART goals. Sign up for automatic retirement contribution and for automatic, plant-based meal delivery from Blue Apron. (I’ve no conflict of interest in these products).

Good ideas all, but I’m suggesting a different approach: Resolve to do something else this year.

Rather than try the same things we’ve attempted, how about selecting something from the bottom of the Marist Poll list – such as resolving to be more humble. Admit when you don’t know something or don’t understand what’s being discussed. Recognize and acknowledge when you’ve screwed up. Or resolve to be more selfless. Add on someone else’s patient, an extra call without expecting a favor in return, or do what you can to help a curbside consult, even if there is no reward or even a small risk to you. Repay the debt you owe your friends, family, colleagues, staff, and patients.

These things are a little trickier to track, but you can find a way to keep yourself accountable. Add a box to your weekly planner that says “Be humble and kind” and check it off for the next 42 weeks. Good news, March 1 falls on a Sunday this year – let’s call it the feast of Akitu.

Happy New Year! And good luck!
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

This column should arrive just in time. By now, you may have already failed some or all of your New Year’s resolutions. By this time in February, eighty percent of us will abort what we resolved to do this year. If this was you, it could be considered a catastrophic failure because not only is it a new year, it is a new decade. That’s right, the opportunity to fix the 10-year-imperfect you won’t come again until 2030!

marekuliasz/iStock/Getty Images

I’m among you. I intended to read fiction daily (starting with “The Great Gatsby,” not “Moby Dick” – I thought I would give myself a fighting chance, but alas ...), to workout at least 5 days every week (I tore my left triangular fibrocartilage complex, so there’s that), to write at least 500 words daily (I’m typing this one-handed: I’m lucky to get 500 letters a day). So I’m out.

If you resolved to do something this year, chances are it was to make a better you: a self-improvement goal such as losing weight, saving more money, or exercising more. According to a Marist Poll, these were the most popular resolutions for 2020. At the bottom of the most-likely-resolutions list were things like “worry less” or “be kinder to others.” These are important goals we’d agree, but we don’t deem them resolution-worthy. Why?

And why do we have New Year’s resolutions in the first place? When I looked into this further, I was surprised by some of the history I discovered.

As far back as the Babylonians, once a year, we’ve tried our best to get better. At the feast of Akitu, the Babylonian new year festival (about March on our modern calendar), people resolved to do a better job of paying debts and returning favors – spin had not been invented, and yoga hadn’t caught on in the Middle East yet. This fundamental desire to be a better human seems hardwired, and long before Bullet Journals we seem to have loved “fresh start” days on the calendar. Yet, we’re doomed to fail, over and over, at least for the last 5,000 or so attempts.

We know so much more now. Put your Nike Renue Fusion shoes next to your bed so you get up and run first thing. Set SMART goals. Sign up for automatic retirement contribution and for automatic, plant-based meal delivery from Blue Apron. (I’ve no conflict of interest in these products).

Good ideas all, but I’m suggesting a different approach: Resolve to do something else this year.

Rather than try the same things we’ve attempted, how about selecting something from the bottom of the Marist Poll list – such as resolving to be more humble. Admit when you don’t know something or don’t understand what’s being discussed. Recognize and acknowledge when you’ve screwed up. Or resolve to be more selfless. Add on someone else’s patient, an extra call without expecting a favor in return, or do what you can to help a curbside consult, even if there is no reward or even a small risk to you. Repay the debt you owe your friends, family, colleagues, staff, and patients.

These things are a little trickier to track, but you can find a way to keep yourself accountable. Add a box to your weekly planner that says “Be humble and kind” and check it off for the next 42 weeks. Good news, March 1 falls on a Sunday this year – let’s call it the feast of Akitu.

Happy New Year! And good luck!
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

The first case of the novel coronavirus, named 2019-nCoV, in the United States has been diagnosed in a traveler from China who came through Seattle-Tacoma International Airport on Jan 15, the Centers for Disease Control and Prevention announced today at a press briefing.

CDC/John Hierholzer, MD

The outbreak began at a animal and meat market in China and now has spread to at least three other countries, including Thailand, Japan and South Korea. While originally thought to be spreading from animal to person, it appears that limited person-to-person transmission is occurring, although it is currently unknown how easily this virus spreads between people.

More than 300 cases have been reported and six deaths have occurred. Fourteen health care workers have been infected.

Scott Lindquist, MD, MPH, Washington state epidemiologist, said at the briefing that the patient, a man who had been in Wuhan, arrived at Sea-Tac on Jan. 15, 2 days before airport screening had been initiated. He was symptom free at the time of his arrival and probably would not have been identified as infected with 2019-nCoV. The patient had been aware of the public health and news media coverage of 2019-nCoV and, after developing symptoms, contacted his health care provider on Jan. 19. The patient did not fly directly from Wuhan, but Dr. Lindquist said that he has been fully cooperative and has been helpful to authorities in tracing his route and contacts. The man is being treated at Providence Regional Medical Center, Everett, Wash.

The CDC obtained a specimen from the patient immediately and identified the 2019-nCoV within 24 hours.

Screening at airports is part of a multipart strategy to address this type of infection that includes public health information dissemination, patient education, as well as hospital preparation and training exercises. Currently, a strategy referred to as “funneling” is being implemented wherein travelers from China are rerouted and reticketed to one of the five airports conducting screening. At present, JFK in New York, San Francisco International, Los Angeles International, Hartsfield-Jackson Atlanta International Airport, and Chicago O’Hare International Airport are conducting inbound traveler screening.

The CDC is working in close cooperation with the Department of Homeland Security and the Federal Aviation Administration to coordinate travel screenings and reroutings. In addition, the CDC is working with the World Health Organization and the international global health community to share information about this outbreak. The CDC also has staff on site in Wuhan and is communicating with local health authorities. The CDC has activated its Emergency Operations Center to better provide ongoing support to the 2019-nCoV response. Currently, the focus is on tracing contacts and the means of transmission of this virus.

Updates on the outbreak will be posted on the CDC coronavirus website.
 

tborden@mdedge.com

CORRECTION: 1/21/2020: The name of the medical center where the 2019-nCoV patient is being treated was corrected.

The first case of the novel coronavirus, named 2019-nCoV, in the United States has been diagnosed in a traveler from China who came through Seattle-Tacoma International Airport on Jan 15, the Centers for Disease Control and Prevention announced today at a press briefing.

CDC/John Hierholzer, MD

The outbreak began at a animal and meat market in China and now has spread to at least three other countries, including Thailand, Japan and South Korea. While originally thought to be spreading from animal to person, it appears that limited person-to-person transmission is occurring, although it is currently unknown how easily this virus spreads between people.

More than 300 cases have been reported and six deaths have occurred. Fourteen health care workers have been infected.

Scott Lindquist, MD, MPH, Washington state epidemiologist, said at the briefing that the patient, a man who had been in Wuhan, arrived at Sea-Tac on Jan. 15, 2 days before airport screening had been initiated. He was symptom free at the time of his arrival and probably would not have been identified as infected with 2019-nCoV. The patient had been aware of the public health and news media coverage of 2019-nCoV and, after developing symptoms, contacted his health care provider on Jan. 19. The patient did not fly directly from Wuhan, but Dr. Lindquist said that he has been fully cooperative and has been helpful to authorities in tracing his route and contacts. The man is being treated at Providence Regional Medical Center, Everett, Wash.

The CDC obtained a specimen from the patient immediately and identified the 2019-nCoV within 24 hours.

Screening at airports is part of a multipart strategy to address this type of infection that includes public health information dissemination, patient education, as well as hospital preparation and training exercises. Currently, a strategy referred to as “funneling” is being implemented wherein travelers from China are rerouted and reticketed to one of the five airports conducting screening. At present, JFK in New York, San Francisco International, Los Angeles International, Hartsfield-Jackson Atlanta International Airport, and Chicago O’Hare International Airport are conducting inbound traveler screening.

The CDC is working in close cooperation with the Department of Homeland Security and the Federal Aviation Administration to coordinate travel screenings and reroutings. In addition, the CDC is working with the World Health Organization and the international global health community to share information about this outbreak. The CDC also has staff on site in Wuhan and is communicating with local health authorities. The CDC has activated its Emergency Operations Center to better provide ongoing support to the 2019-nCoV response. Currently, the focus is on tracing contacts and the means of transmission of this virus.

Updates on the outbreak will be posted on the CDC coronavirus website.
 

tborden@mdedge.com

CORRECTION: 1/21/2020: The name of the medical center where the 2019-nCoV patient is being treated was corrected.

The first case of the novel coronavirus, named 2019-nCoV, in the United States has been diagnosed in a traveler from China who came through Seattle-Tacoma International Airport on Jan 15, the Centers for Disease Control and Prevention announced today at a press briefing.

CDC/John Hierholzer, MD

The outbreak began at a animal and meat market in China and now has spread to at least three other countries, including Thailand, Japan and South Korea. While originally thought to be spreading from animal to person, it appears that limited person-to-person transmission is occurring, although it is currently unknown how easily this virus spreads between people.

More than 300 cases have been reported and six deaths have occurred. Fourteen health care workers have been infected.

Scott Lindquist, MD, MPH, Washington state epidemiologist, said at the briefing that the patient, a man who had been in Wuhan, arrived at Sea-Tac on Jan. 15, 2 days before airport screening had been initiated. He was symptom free at the time of his arrival and probably would not have been identified as infected with 2019-nCoV. The patient had been aware of the public health and news media coverage of 2019-nCoV and, after developing symptoms, contacted his health care provider on Jan. 19. The patient did not fly directly from Wuhan, but Dr. Lindquist said that he has been fully cooperative and has been helpful to authorities in tracing his route and contacts. The man is being treated at Providence Regional Medical Center, Everett, Wash.

The CDC obtained a specimen from the patient immediately and identified the 2019-nCoV within 24 hours.

Screening at airports is part of a multipart strategy to address this type of infection that includes public health information dissemination, patient education, as well as hospital preparation and training exercises. Currently, a strategy referred to as “funneling” is being implemented wherein travelers from China are rerouted and reticketed to one of the five airports conducting screening. At present, JFK in New York, San Francisco International, Los Angeles International, Hartsfield-Jackson Atlanta International Airport, and Chicago O’Hare International Airport are conducting inbound traveler screening.

The CDC is working in close cooperation with the Department of Homeland Security and the Federal Aviation Administration to coordinate travel screenings and reroutings. In addition, the CDC is working with the World Health Organization and the international global health community to share information about this outbreak. The CDC also has staff on site in Wuhan and is communicating with local health authorities. The CDC has activated its Emergency Operations Center to better provide ongoing support to the 2019-nCoV response. Currently, the focus is on tracing contacts and the means of transmission of this virus.

Updates on the outbreak will be posted on the CDC coronavirus website.
 

tborden@mdedge.com

CORRECTION: 1/21/2020: The name of the medical center where the 2019-nCoV patient is being treated was corrected.

During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?

On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.

The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.

Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.

A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.

In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.

“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.

Tramadol plus celecoxib gains some support

The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.

In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”

Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.

Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.

“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.

But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.

“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.

Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.

“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.

“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.

“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.

What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.

“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.

Two other opioids faced greater opposition

The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.

“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.

The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.

“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.

“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,

The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.

“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.

“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.

Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.

“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”

mzoler@mdedge.com

During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?

On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.

The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.

Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.

A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.

In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.

“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.

Tramadol plus celecoxib gains some support

The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.

In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”

Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.

Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.

“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.

But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.

“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.

Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.

“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.

“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.

“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.

What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.

“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.

Two other opioids faced greater opposition

The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.

“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.

The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.

“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.

“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,

The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.

“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.

“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.

Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.

“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”

mzoler@mdedge.com

During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?

On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.

The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.

Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.

A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.

In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.

“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.

Tramadol plus celecoxib gains some support

The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.

In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”

Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.

Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.

“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.

But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.

“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.

Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.

“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.

“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.

“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.

What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.

“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.

Two other opioids faced greater opposition

The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.

“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.

The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.

“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.

“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,

The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.

“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.

“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.

Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.

“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”

mzoler@mdedge.com