Another use for the intense pulsed-light device, pulsed-dye laser, and potassium titanyl phosphate laser in clinical practice is for treating patients who have dry eye, even if you are not an ophthalmologist, suggests R. Rox Anderson, MD.

“I’ve been doing this in my practice for a number of years and it’s quite gratifying,” Dr. Anderson, a dermatologist who directs the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “You treat the periorbital skin, mostly under the eye, just as if you were treating telangiectasia rosacea. The meibomian glands under the upper eyelid that cause this disease are sebaceous glands, and most of the people with dry eye have rosacea.”

In a retrospective noncomparative, interventional case series, 78 patients with severe dry eye syndrome were treated with intense pulsed-light therapy and gland expression at a single outpatient clinic over 30 months. Physician-judged improvement in dry eye tear breakup time was found for 87% of patients with an average of seven treatment visits and four maintenance visits, while 93% of patients reported posttreatment satisfaction with the degree of dry eye syndrome symptoms. More information about the approach were published in Investigative Ophthalmology & Visual Science and Current Opinion in Ophthalmology.

“What’s gratifying here is that most patients will get about 2 months of relief after a single treatment,” Dr. Anderson said. “They are very happy – some of the happiest patients in my practice. Many ophthalmologists don’t have the technology, so I think you can do this depending on your local referral system.”

Light-based approaches are also making promising inroads in cancer treatment. A recent study led by Martin Purschke, PhD, at the Wellman Center evaluated the use of a novel radio-phototherapy approach for killing cancer cells. The center of solid tissue tumors that are treated with radiotherapy is hypoxic, Dr. Anderson explained, “and oxygen is typically located around the perimeter of the tumor. After a radiation therapy treatment, you kill only the outer portion of it, and then the remaining cells grow back, and you end up with the same tumor. This is why you have to do radiation therapy over and over again. In contrast, if you add scintillating nanoparticles, which are particles with a very high C number atoms in them that pick up the x-ray photon and then emit many UV photons from one x-ray photon, they are very efficient at converting x-ray energy to UV energy.” The x-ray, he added, “generates UV light, and the UV light kills the tumor. We’re hoping that we can make a dent in radiotherapy this way.”

Dr. Anderson predicted that fiber lasers, which are highly advanced for industrial applications, will play an increasing role in dermatology and in other areas of medicine. “There are not a new kid on the block anymore but fiber lasers are relatively new to medicine,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “We are seeing incredible capabilities with fiber lasers: essentially any wavelength, any power, any pulse duration you want. The lasers are efficient, small, rugged, and their lifetime exceeds your lifetime. They are likely to displace many of our old lasers in dermatology. I don’t know when, but I know it will happen.”

He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Another use for the intense pulsed-light device, pulsed-dye laser, and potassium titanyl phosphate laser in clinical practice is for treating patients who have dry eye, even if you are not an ophthalmologist, suggests R. Rox Anderson, MD.

“I’ve been doing this in my practice for a number of years and it’s quite gratifying,” Dr. Anderson, a dermatologist who directs the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “You treat the periorbital skin, mostly under the eye, just as if you were treating telangiectasia rosacea. The meibomian glands under the upper eyelid that cause this disease are sebaceous glands, and most of the people with dry eye have rosacea.”

In a retrospective noncomparative, interventional case series, 78 patients with severe dry eye syndrome were treated with intense pulsed-light therapy and gland expression at a single outpatient clinic over 30 months. Physician-judged improvement in dry eye tear breakup time was found for 87% of patients with an average of seven treatment visits and four maintenance visits, while 93% of patients reported posttreatment satisfaction with the degree of dry eye syndrome symptoms. More information about the approach were published in Investigative Ophthalmology & Visual Science and Current Opinion in Ophthalmology.

“What’s gratifying here is that most patients will get about 2 months of relief after a single treatment,” Dr. Anderson said. “They are very happy – some of the happiest patients in my practice. Many ophthalmologists don’t have the technology, so I think you can do this depending on your local referral system.”

Light-based approaches are also making promising inroads in cancer treatment. A recent study led by Martin Purschke, PhD, at the Wellman Center evaluated the use of a novel radio-phototherapy approach for killing cancer cells. The center of solid tissue tumors that are treated with radiotherapy is hypoxic, Dr. Anderson explained, “and oxygen is typically located around the perimeter of the tumor. After a radiation therapy treatment, you kill only the outer portion of it, and then the remaining cells grow back, and you end up with the same tumor. This is why you have to do radiation therapy over and over again. In contrast, if you add scintillating nanoparticles, which are particles with a very high C number atoms in them that pick up the x-ray photon and then emit many UV photons from one x-ray photon, they are very efficient at converting x-ray energy to UV energy.” The x-ray, he added, “generates UV light, and the UV light kills the tumor. We’re hoping that we can make a dent in radiotherapy this way.”

Dr. Anderson predicted that fiber lasers, which are highly advanced for industrial applications, will play an increasing role in dermatology and in other areas of medicine. “There are not a new kid on the block anymore but fiber lasers are relatively new to medicine,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “We are seeing incredible capabilities with fiber lasers: essentially any wavelength, any power, any pulse duration you want. The lasers are efficient, small, rugged, and their lifetime exceeds your lifetime. They are likely to displace many of our old lasers in dermatology. I don’t know when, but I know it will happen.”

He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Another use for the intense pulsed-light device, pulsed-dye laser, and potassium titanyl phosphate laser in clinical practice is for treating patients who have dry eye, even if you are not an ophthalmologist, suggests R. Rox Anderson, MD.

“I’ve been doing this in my practice for a number of years and it’s quite gratifying,” Dr. Anderson, a dermatologist who directs the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “You treat the periorbital skin, mostly under the eye, just as if you were treating telangiectasia rosacea. The meibomian glands under the upper eyelid that cause this disease are sebaceous glands, and most of the people with dry eye have rosacea.”

In a retrospective noncomparative, interventional case series, 78 patients with severe dry eye syndrome were treated with intense pulsed-light therapy and gland expression at a single outpatient clinic over 30 months. Physician-judged improvement in dry eye tear breakup time was found for 87% of patients with an average of seven treatment visits and four maintenance visits, while 93% of patients reported posttreatment satisfaction with the degree of dry eye syndrome symptoms. More information about the approach were published in Investigative Ophthalmology & Visual Science and Current Opinion in Ophthalmology.

“What’s gratifying here is that most patients will get about 2 months of relief after a single treatment,” Dr. Anderson said. “They are very happy – some of the happiest patients in my practice. Many ophthalmologists don’t have the technology, so I think you can do this depending on your local referral system.”

Light-based approaches are also making promising inroads in cancer treatment. A recent study led by Martin Purschke, PhD, at the Wellman Center evaluated the use of a novel radio-phototherapy approach for killing cancer cells. The center of solid tissue tumors that are treated with radiotherapy is hypoxic, Dr. Anderson explained, “and oxygen is typically located around the perimeter of the tumor. After a radiation therapy treatment, you kill only the outer portion of it, and then the remaining cells grow back, and you end up with the same tumor. This is why you have to do radiation therapy over and over again. In contrast, if you add scintillating nanoparticles, which are particles with a very high C number atoms in them that pick up the x-ray photon and then emit many UV photons from one x-ray photon, they are very efficient at converting x-ray energy to UV energy.” The x-ray, he added, “generates UV light, and the UV light kills the tumor. We’re hoping that we can make a dent in radiotherapy this way.”

Dr. Anderson predicted that fiber lasers, which are highly advanced for industrial applications, will play an increasing role in dermatology and in other areas of medicine. “There are not a new kid on the block anymore but fiber lasers are relatively new to medicine,” he said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “We are seeing incredible capabilities with fiber lasers: essentially any wavelength, any power, any pulse duration you want. The lasers are efficient, small, rugged, and their lifetime exceeds your lifetime. They are likely to displace many of our old lasers in dermatology. I don’t know when, but I know it will happen.”

He reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

Medication overuse headache presents difficult challenges for both patients and physicians. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.

These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.

The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.

Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
 

Is medication overuse really the culprit?

Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.

Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.

He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.

Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.

Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.

“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.

A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.

He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”

To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.

He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
 

Medication overuse is to blame

Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.

Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.

She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.

Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.

Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.

These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.

Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.

Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
 

Common ground

Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.

In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.

In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.

“I absolutely agree with that,” responded Dr. Nye.

Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.

Medication overuse headache presents difficult challenges for both patients and physicians. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.

These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.

The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.

Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
 

Is medication overuse really the culprit?

Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.

Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.

He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.

Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.

Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.

“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.

A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.

He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”

To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.

He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
 

Medication overuse is to blame

Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.

Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.

She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.

Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.

Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.

These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.

Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.

Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
 

Common ground

Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.

In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.

In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.

“I absolutely agree with that,” responded Dr. Nye.

Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.

Medication overuse headache presents difficult challenges for both patients and physicians. Physicians worry about episodic migraine converting to chronic daily headache, but this worry can also lead to under-treatment and even stigmatization of patients who aggressively treat their symptoms.

These concerns and others were a topic of a debate at the Headache Cooperative of New England’s 20th Annual HCNE Boston Fall Headache Symposium, which was conducted virtually.

The International Classification of Headache-3 (ICHD-3) defines medication overuse headache as a headache that occurs on 15 or more days per month in a patient with pre-existing primary headache, and that develops because of regular overuse of acute or symptomatic headache medication. The ICHD-3 also says that headache usually resolves when overuse is stopped, though not always.

Paul Rizzoli, MD, took issue with that definition. “If you have a lot of headaches and you take medication for them, then you likely have medication overuse headache. They say the most common cause of symptoms suggestive of chronic migraine is medication overuse. That’s like saying, if you have a rash on your arm, then it is an allergic sun exposure rash. No need to characterize the rash,” said Dr. Rizzoli, who is clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, during the session.
 

Is medication overuse really the culprit?

Dr. Rizzoli began by emphasizing that taking a lot of medication is always a concern. “Significant hepatic and renal and GI toxicities can result from taking and overusing medication of all sorts. What (I am) questioning is whether or not this rather strange, arbitrary, fluidly-defined concept of abortive migraine medicine overuse is truly responsible for causing all of the ills of which it is accused – and just as importantly, if the proposed solution for it, which is to just stop the overused medication and all will be better – if that solution is the right or wrong advice to give to a patient,” he said.

Much of Dr. Rizzoli’s criticism rested on the definition of medication overuse syndrome. He believes that many concerns about medication overuse can be traced to the use of opiates or barbiturate-containing medications, which have known propensities to lead to headaches. Other cases are less well defined, and “it’s not quite clear what the pathophysiology of the condition is – whether or not it’s the same as rebound or withdrawal headache, or if it is the same as a pronociceptive effect of analgesics, also called medicine-induced headache. Both are well documented and accepted, and the idea of opioid-induced analgesia tolerance is well documented and has several plausible mechanisms attributed to it,” said Dr. Rizzoli.

He said that changes in structural imaging in the brain suggest there at least two subgroups of patients that are both labeled as having medication overuse headache, one from medication overuse and one from progression of migraine disease. “Based on physiology, medication overuse headache cannot be clearly seen as a unitary condition,” he said.

Dr. Rizzoli cited other research on triptans, opioids, and barbiturates that showed an overall conversion from episodic migraine to chronic migraine, with the lowest frequency occurring in patients taking acetaminophen, aspirin, and caffeine (2%), followed by NSAIDs (4%), triptans (4%), opioids (5%), and barbiturates (6%). A total of 52 patients who became chronic were taking triptans, on average 7 days per month. The 1,370 triptan-using patients who remained episodic took triptans on average 5 days per month. “Does this seem like a huge difference between these two groups? The transformation rate in just this triptan subgroup was about 3%-4%, suggesting that, compared with the overall transformation rate of 3%, use of triptans did not exert much force overall on the baseline rate,” he said. Similar patterns were visible with use of other classes of drugs.

Meanwhile, the higher rates of conversion seen with opioids and barbiturates suggests an effect from these drugs. “Perhaps this data suggests the previously known effect is at play here and argues against the need for a separate diagnosis of medication overuse headache,” Dr. Rizzoli said.

“The evidence that simple analgesics can cause medication overuse headache is especially weak, and the evidence that NSAIDs do is conflicting, with some evidence suggesting they’re protective at some doses.” Other population studies suggested most patients with daily headache do not overuse medications, and studies in India, where analgesics are rarely used, still showed a similar rate of conversion to daily headache. Other studies failed to show evidence that withdrawal of overused medication leads to improvement. “Studies of populations after aggressive management of medicine overuse headache indicate that, for the majority of the headaches, for the most part did not clear after treatment, except maybe for a short time,” said Dr. Rizzoli.

A systematic review of 18 population studies showed the prevalence of medical overuse headache ranged from 11% to 68%. “That indicates substantial uncertainty about the magnitude of the problem,” said Dr. Rizzoli.

He also noted potential harms to patients. Many patients come in experience between 10 and 20 headaches per month. “To see them out of medical overuse would have us advising not to treat half of their headaches monthly in order to avoid this evil. Many patients who have read or heard about this condition are themselves restricting treatment so as to avoid medication overuse headache. The harms of such undertreatment have not been fully investigated.”

To get at the issue, he recommended adapting the traditional number-needed-to-treat calculation. “You could calculate a number needed to overtreat. If medication use is assumed to be the sole cause of headache chronification, the calculations could suggest you would need to restrict therapy for about 4 people for each person you protect from going chronic. That’s a lot of undertreatment,” said Dr. Rizzoli.

He summed up by saying that some patients may have a progressive disorder with structure and physiological changes in the brain that result in chronic pain, and such patients should be identified and studied. In others with frequent headache, high medication use may simply be associated with the condition becoming chronic, but not causative. “These diagnostic groups may be mixed and may be difficult to untangle,” said Dr. Rizzoli.
 

Medication overuse is to blame

Dr. Rizzoli’s debate lecture was followed by Barbara Nye, MD, who argued that concerns over medication overuse headache are valid. She noted a more unifying definition in ICHD-3, which requires regular medication overuse for at least 3 months, along with primary headache disorder.

Dr. Nye, who is codirector of the Headache Clinic at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., related her experience that medication overuse headache often occurs more quickly than the 3-month time frame contained in ICHD-3, especially in patients who were given pain medications after undergoing surgery. She echoed Dr. Rizzoli’s concerns about opiates and barbiturates. “Medicine overuse headache should be something we focus on, and we should be warning providers both in neurology and primary care about the frequent use of opiate and butalbital-containing medications, and frequent over-the-counter medicine use in high-frequency headache disorders,” Dr. Nye said during her talk.

She cited research showing risk factors for conversion from episodic to chronic daily headache. As well as medication overuse, these include White race, lower education status, previous marriage, obesity, diabetes, arthritis, top-quartile caffeine use, stressful life events, and higher headache frequency.

Risks vary by medication class. Opiates and narcotics used more than 2 or 3 times per week are of particular concern, as are short-acting over-the-counter medicines used more than three times per week or 10-15 days per month. She agreed that NSAIDs may have a protective effect, but only at much lower doses and when used about five (or fewer) times per month. One study showed a possible protection effect of NSAIDs, though when used more than 10 days/month, they were associated with medication overuse headache.

Fioricet and Fiorinal, used more than 1 day/week, have an early and robust medicine overuse effect. “Limiting that use is very important,” said Dr. Nye. Other medicines and doses of concern include Tramadol/Ultram used at a higher than 50 mg/day dose, which has a metabolite that causes headache, and triptans used more than 10 days/month.

These concerns came about after analysis of large trials in patients with other conditions who also suffer from episodic migraines. A study of patients with irritable bowel syndrome and migraine showed a risk of conversion with opioid treatment. Another study of patients with arthritis and episodic migraine showed an association between conversion and NSAIDs alone, NSAIDs combined with Tylenol, and NSAIDs combined with opioids.

Risks of medication overuse also included collateral damage to the gastrointestinal and kidney systems, development of dependence, exacerbation of depression, and opioid-induced hyperalgesia, according to Dr. Nye. The overused medication may also interfere with the use of preventive medication. Those concerns drive the conventional wisdom of weaning patients off the overused medication, Dr. Nye said.

Dr. Nye discussed some of the observations of structural changes in the brain found in episodic migraine and chronic migraine associated with medication overuse. Functional MRI showed changes in grey matter, both as a result of medication overuse headache and further changes after medication withdrawal. “A lot of neuroplasticity and neuroadaptation occurs, and these effects seem to be sustained anywhere from 4-6 months after (medicine) discontinuation,” said Dr. Nye.
 

Common ground

Dr. Nye emphasized the need to be aware of the dangers of medication overuse headache, but noted that clinicians should address the problem to ensure that patients are empowered, potentially providing preventive medications and encouraging more effective use of daily abortive medications.

In response, Dr. Rizzoli suggested that the two agreed on many issues. For her part, Dr. Nye agreed that medication overuse headache is a muddy concept that needs more research to understand the relationship between opiate use and chronic migraine, “but I do think there have been some good studies of fMRI evaluating the difference between those with medication overuse headache and seeing how they convert back to a different underlying network (following medication withdrawal). I do agree that there is probably a subpopulation that is not affected by medication overuse headache,” Dr. Nye said.

In the end, both expressed concerns for the patient. “I share Barbara’s concern that we need to be mindful and protect our patients from medication use, but on the other hand I think we also need to protect our patients from the complications of having a diagnosis of medical overuse and the stigmatization that goes with that. That particular issue goes both ways,” said Dr. Rizzoli.

“I absolutely agree with that,” responded Dr. Nye.

Dr. Nye is on the advisory boards for Biohaven, Upsher Smith, and Impel. She is a trial site principal investigator for Allergan, Amgen, and Satsuma. Dr. Rizzoli has been a consultant for Nestle and served on the scientific advisory or data safety monitoring board for Biohaven and Xoc Pharma. He has also received research support from Allergan.

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

“We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too,” said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Dr. Taddei and colleagues Silvia Vilarinho, MD, PhD; Simona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.
 

Cirrhosis and portal hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

“This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease,” Dr. Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

“While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology,” Dr. Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy “is of no utility,” (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).
 

Alcohol

The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

“They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship,” Dr. Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

“Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD,” she said (Abstract #7).
 

Transplantation

The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were “identical, and excellent.” In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm (P­ < .001).

“Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms,” Dr. Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new “safety net” policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.
 

Autoimmune & cholestatic diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

“The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus,” Dr. Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that “Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations.”

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

“Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant,” Dr. Taddei said (Abstract #97).
 

Drug-induced liver injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

“High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge,” Dr. Taddei said (Abstract # 116).
 

Neoplasia

The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).

COVID-19

Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Dr. Taddei reported having no disclosures.

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

“We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too,” said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Dr. Taddei and colleagues Silvia Vilarinho, MD, PhD; Simona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.
 

Cirrhosis and portal hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

“This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease,” Dr. Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

“While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology,” Dr. Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy “is of no utility,” (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).
 

Alcohol

The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

“They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship,” Dr. Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

“Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD,” she said (Abstract #7).
 

Transplantation

The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were “identical, and excellent.” In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm (P­ < .001).

“Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms,” Dr. Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new “safety net” policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.
 

Autoimmune & cholestatic diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

“The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus,” Dr. Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that “Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations.”

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

“Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant,” Dr. Taddei said (Abstract #97).
 

Drug-induced liver injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

“High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge,” Dr. Taddei said (Abstract # 116).
 

Neoplasia

The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).

COVID-19

Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Dr. Taddei reported having no disclosures.

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

“We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too,” said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Dr. Taddei and colleagues Silvia Vilarinho, MD, PhD; Simona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.
 

Cirrhosis and portal hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

“This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease,” Dr. Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

“While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology,” Dr. Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy “is of no utility,” (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).
 

Alcohol

The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

“They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship,” Dr. Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

“Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD,” she said (Abstract #7).
 

Transplantation

The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were “identical, and excellent.” In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm (P­ < .001).

“Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms,” Dr. Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new “safety net” policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.
 

Autoimmune & cholestatic diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

“The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus,” Dr. Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that “Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations.”

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

“Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant,” Dr. Taddei said (Abstract #97).
 

Drug-induced liver injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

“High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge,” Dr. Taddei said (Abstract # 116).
 

Neoplasia

The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).

COVID-19

Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Dr. Taddei reported having no disclosures.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

Migraine aura sometimes accompanies or precedes migraine pain, but the phenomenon is difficult to treat and poorly understood. However, some evidence points to potential neurological mechanisms, and migraine aura is associated with cardiovascular disease risk.

“We now have an accumulating body of evidence that supports cortical spreading depression (CSD) as the underlying pathophysiological event of migraine aura,” Andrea Harriott, MD, PhD, said at the Stowe Headache Symposium sponsored by the Headache Cooperative of New England, which was conducted virtually. Dr. Harriott is assistant professor of neurology at Massachusetts General Hospital in Boston.

Somewhere between 20% and 40% of patients with migraine experience aura. It is most often visual, though it can also include sensory, aphasic, and motor symptoms. Visual aura usually begins as a flickering zigzag pattern in the central visual field that moves slowly toward the periphery and often leaves a scotoma. Typical duration is 15-30 minutes. Aura symptoms are more common in females.

Research in the 1940s conducted by the Brazilian researcher Aristides de Azevedo Pacheco Leão, PhD, then at Harvard Medical School, Boston, showed evidence of CSD in rabbits after electrical or mechanical stimulation. He observed a wave of vasodilation and increased blood flow over the cortex that spread over nearly the entire dorsolateral cortex within 3-6 minutes.

In the 1940s and 1950s, researchers sketched on paper the visual disturbance over 10 minutes, tracking the expanding spectrum across the visual field, from the center toward the periphery. The resulting scotoma advanced across the visual cortex at a rate very similar to that of the cortical spreading observed by Dr. Leão, “potentially linking this electrical event that was described with the aura event of migraine,” said Dr. Harriott. Those researchers hypothesized that the aura was produced by a strong excitation phase, followed by a wave of total inhibition.

More recent functional magnetic resonance imaging studies have also shown that CSD-like disturbances occur when patients experience migraine aura. In one study, researchers observed an initial increase and then a decrease in the blood oxygenation level dependent (BOLD) signal, which spread slowly across the visual cortex and correlated with the aura event. “This study was really important in confirming that a CSD-like phenomenon was likely the underlying perturbation that produced the visual aura of migraine,” said Dr. Harriott.

Despite the evidence that CSD causes migraine aura, its connection to migraine pain hasn’t been firmly established. But Dr. Harriott presented some evidence linking the two. Migraine aura is usually followed by pain, and aura precedes migraine attacks 78%-93% of the time. Cephalic allodynia occurs in migraine about 70% to 80% of the time, and migraine with aura is more often associated with severe cutaneous allodynia than is migraine without aura. Finally, migraine patients with comorbidities have more severe disability, and more frequent cutaneous allodynia and aura than does the general migraine population (40% vs. 29%).

All of that suggests that activation of trigeminal nociceptors is involved with migraine aura, according to Dr. Harriott. Preclinical studies have also suggested links between CSD and activation of trigeminal nociceptors, with both immunohistochemical and electrophysiological lines of evidence. “These data suggest that spreading depression actually activates trigeminal nociceptors that we know are involved in signal pain in the head and neck, and that we know are involved in cephalic allodynia as well,” Dr. Harriott said.

The evidence impressed Allan Purdy, MD, professor of medicine at Dalhousie University, Halifax, N.S., who was the discussant for the presentation. “It’s an excellent case that CSD is a remarkably good correlate for aura,” he said during the session.

Along with potential impacts on migraine pain, aura is also associated with cardiovascular risk. “This is really important to know about in our clinical population,” said Dr. Harriott.

Meta-analyses of case control and cohort studies have shown associations between migraine aura and vascular disorders such as ischemic stroke. One meta-analysis showed about a twofold increased risk associated with migraine compared with the nonmigraine population. This difference was driven by migraine with aura (relative risk [RR], 2.25; 95% confidence interval [CI], 1.53-3.33) rather than migraine without aura (RR, 1.24; 95% CI, 0.86-1.79). Migraine generally is associated with greater risk of myocardial infarction (adjusted hazard ratio, 1.33; 95% CI, 1.08-1.64), and that association may be stronger in the aura phenotype.

There doesn’t appear to be evidence that traditional risk factors for heart disease – such as hypertension, diabetes, or high cholesterol – play a role in the association between aura and heart disease. One possibility is that variables like platelet activation, hypercoagulable state, or genetic susceptibility could be responsible.

The risks associated with migraine aura should be noted, but with a caveat, according to Dr. Purdy. “Even though the relative risk is high, the absolute risk is still relatively low, and patients with migraine with aura, who smoke or are female and over 45, those are the cases where the worry comes in.”

Dr. Harriott and Dr. Purdy have nothing to disclose.

The US Food and Drug Administration (FDA) has expanded the indication for the antiviral baloxavir marboxil (Xofluza) to include postexposure prophylaxis of uncomplicated influenza in people aged 12 years and older.

“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” Debra Birnkrant, MD, director, Division of Antiviral Products, FDA Center for Drug Evaluation and Research, said in a press release.

In addition, Xofluza, which was previously available only in tablet form, is also now available as granules for mixing in water, the FDA said.

The agency first approved baloxavir marboxil in 2018 for the treatment of acute uncomplicated influenza in people aged 12 years or older who have been symptomatic for no more than 48 hours.

A year later, the FDA expanded the indication to include people at high risk of developing influenza-related complications, such as those with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity, as well as adults aged 65 years or older.

The safety and efficacy of Xofluza for influenza postexposure prophylaxis is supported by a randomized, double-blind, controlled trial involving 607 people aged 12 years and older. After exposure to a person with influenza in their household, they received a single dose of Xofluza or placebo.

The primary endpoint was the proportion of individuals who became infected with influenza and presented with fever and at least one respiratory symptom from day 1 to day 10.

Of the 303 people who received Xofluza, 1% of individuals met these criteria, compared with 13% of those who received placebo.

The most common adverse effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

Hypersensitivity, including anaphylaxis, can occur in patients taking Xofluza. The antiviral is contraindicated in people with a known hypersensitivity reaction to Xofluza.

Xofluza should not be coadministered with dairy products, calcium-fortified beverages, laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminium, or zinc.

Full prescribing information is available online.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the antiviral baloxavir marboxil (Xofluza) to include postexposure prophylaxis of uncomplicated influenza in people aged 12 years and older.

“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” Debra Birnkrant, MD, director, Division of Antiviral Products, FDA Center for Drug Evaluation and Research, said in a press release.

In addition, Xofluza, which was previously available only in tablet form, is also now available as granules for mixing in water, the FDA said.

The agency first approved baloxavir marboxil in 2018 for the treatment of acute uncomplicated influenza in people aged 12 years or older who have been symptomatic for no more than 48 hours.

A year later, the FDA expanded the indication to include people at high risk of developing influenza-related complications, such as those with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity, as well as adults aged 65 years or older.

The safety and efficacy of Xofluza for influenza postexposure prophylaxis is supported by a randomized, double-blind, controlled trial involving 607 people aged 12 years and older. After exposure to a person with influenza in their household, they received a single dose of Xofluza or placebo.

The primary endpoint was the proportion of individuals who became infected with influenza and presented with fever and at least one respiratory symptom from day 1 to day 10.

Of the 303 people who received Xofluza, 1% of individuals met these criteria, compared with 13% of those who received placebo.

The most common adverse effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

Hypersensitivity, including anaphylaxis, can occur in patients taking Xofluza. The antiviral is contraindicated in people with a known hypersensitivity reaction to Xofluza.

Xofluza should not be coadministered with dairy products, calcium-fortified beverages, laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminium, or zinc.

Full prescribing information is available online.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the indication for the antiviral baloxavir marboxil (Xofluza) to include postexposure prophylaxis of uncomplicated influenza in people aged 12 years and older.

“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” Debra Birnkrant, MD, director, Division of Antiviral Products, FDA Center for Drug Evaluation and Research, said in a press release.

In addition, Xofluza, which was previously available only in tablet form, is also now available as granules for mixing in water, the FDA said.

The agency first approved baloxavir marboxil in 2018 for the treatment of acute uncomplicated influenza in people aged 12 years or older who have been symptomatic for no more than 48 hours.

A year later, the FDA expanded the indication to include people at high risk of developing influenza-related complications, such as those with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity, as well as adults aged 65 years or older.

The safety and efficacy of Xofluza for influenza postexposure prophylaxis is supported by a randomized, double-blind, controlled trial involving 607 people aged 12 years and older. After exposure to a person with influenza in their household, they received a single dose of Xofluza or placebo.

The primary endpoint was the proportion of individuals who became infected with influenza and presented with fever and at least one respiratory symptom from day 1 to day 10.

Of the 303 people who received Xofluza, 1% of individuals met these criteria, compared with 13% of those who received placebo.

The most common adverse effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

Hypersensitivity, including anaphylaxis, can occur in patients taking Xofluza. The antiviral is contraindicated in people with a known hypersensitivity reaction to Xofluza.

Xofluza should not be coadministered with dairy products, calcium-fortified beverages, laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminium, or zinc.

Full prescribing information is available online.

This article first appeared on Medscape.com.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

A limited number of high-quality studies demonstrate the efficacy of microneedling, but it’s a good alternative to lasers, especially for darker skin types, according to Catherine M. DiGiorgio, MD, MS.

During a virtual course on laser and aesthetic skin therapy, Dr. DiGiorgio, a laser and cosmetic dermatologist at the Boston Center for Facial Rejuvenation, provided a state-of-the-art update on microneedling, a procedure in which microneedles are rolled over the skin to create epidermal and dermal microwounds.

“The depths are adjustable and it’s purely mechanical: no energy is being delivered with these treatments,” she said. “The hypothesized mechanism of action is that microneedling creates microwounds which initiate wound healing to stimulate new collagen production. This breaks apart compact collagen in the superficial dermis while stimulating new collagen and elastin,” she explained, adding that it is also hypothesized that this “stimulates growth factors that directly impact collagen and elastin synthesis.”

Conditions that have been reported to be treatable with microneedling in the medical literature include scars – especially acne scars – as well as rhytides, skin laxity, striae, melasma, and enlarged pores. Microneedling can also be used for transdermal drug delivery, although it’s far inferior to microinjection of medications. Contraindications are similar to those with laser surgery, including active infection of the area, history of keloids, inflammatory acne, and immunosuppression; and it should not be performed on the same day as neuromodulator treatment, to avoid diffusion of the neuromodulator. Herpes simplex virus prophylaxis is also indicated prior to microneedling treatment.

Many devices are available for use, including fixed, manual needle rollers and electric-powered pens with single-use sterile cartridges. The devices vary by needle length, quantity, diameter, configuration, and material of which the microneedles are made of. The needle length is not reliable for penetration depth, especially when greater than 1 mm. Treatment guidelines vary based on the area being treated.

“You put tension on the skin and apply the device perpendicularly,” Dr. DiGiorgio said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “It should be performed in quadrants, and I prefer to treat in cosmetic units. The endpoint is pinpoint bleeding versus deep purpura. Ice water–soaked sterile gauze can be applied after treatment and skin care can be resumed in 5-7 days.”

In an effort to compare the efficacy and safety of the 2940-nm Er:YAG laser and microneedling for the treatment of atrophic acne scars, researchers in Egypt performed a randomized, split-face study in 30 patients. Study participants were evaluated by two blinded physicians at baseline and at 3 months follow-up. Both modalities showed a significant improvement in acne scars, but those treated with the Er:YAG laser showed a statistically significant greater improvement (70% vs. 30%, respectively; P < .001). Histology revealed a significantly higher increase in the mean quantity of collagen fibers in the Er:YAG-treated patients, compared with those who underwent microneedling, but patients in the microneedling group experienced less erythema and edema. Pain scores were significantly higher in the microneedling group compared with the Er:YAG group.

In a more recent study, researchers performed a systematic review of 37 articles in the medical literature related to microneedling. They found that the procedure provides good results when used on its own, and is preferred by patients because of its minimal downtime and side effects. However, they concluded that, while microneedling is a safe and effective option, methodological shortcomings and further research is required to establish it as an evidence-based therapeutic option.

“There are a limited number of high-quality studies demonstrating the efficacy of microneedling,” Dr. DiGiorgio said. “It is a safe procedure, which could complement laser treatments, so you could perform it between expensive and high-downtime lasers. It is an option for patients who seek measurable results with little to no downtime, and it’s also an option for clinicians who do not use laser-resurfacing devices. Basically, further research is needed to establish microneedling as an evidence-based therapeutic option. Laser continues to remain the gold standard for treatment.”

Another treatment option is fractional microneedling with radiofrequency (RF). These are microneedles which deliver energy in the form of RF at the tip of the needle, which denatures collagen and creates thermal coagulative injury zones at temperatures greater than 65° C. The microneedles can be insulated or noninsulated. “Insulated tips are safer for darker skin types because the epidermis is protected from the heat damage,” Dr. DiGiorgio said.

These treatments are used for the improvement of rhytides and scars and for skin tightening. “The treatments are painful and require topical anesthesia,” she said. “Erythema can range from about 24 hours to 4 days depending on the device being used. Usually monthly treatments are recommended.”

A study by investigators in South Korea and China set out to analyze histometric changes of this approach in pigs. They treated the pigs with a fractional microneedle delivery system at various depths, conduction times, and energies, and performed punch biopsies immediately after treatment, 4 days post treatment, and at 2 weeks post treatment. They noted that depth and conduction time affected the height, width, and volume of the columns of coagulation, but that the energy only affected the level of tissue destruction. “They also noted that RF-induced coagulated columns had a mixed cellular infiltrate, neovascularization, granular tissue formation with fibroblasts, and neocollagenesis and elastogenesis in the dermis,” Dr. DiGiorgio said.

In another study, researchers in Thailand performed a study in two women who were going to undergo abdominoplasty. Participants received six treatments prior to abdominoplasty with biopsies at different time intervals following microneedling with radiofrequency. The researchers tested five energy levels and five test areas; no collagen denaturization was observed with microneedling alone.

“This supports the idea that heat is required to stimulate neocollagenesis, and needles alone do not denature collagen,” Dr. DiGiorgio said. “They also found that neocollagenesis and neoelastogenesis occurred at optimal heating levels.”

In a separate study, researchers from Denmark used a number of different imaging modalities to evaluate the impact of microneedle fractional RF-induced micropores. When they used reflectance confocal microscopy, they observed that the micropores showed a concentric shape. “They contained hyper-reflective granules, and the coagulated tissue was seen from the epidermis to the dermal-epidermal junction,” Dr. DiGiorgio said. “This was not seen in the low energy microneedle RF. On optical coherence tomography, they noted that high-energy needle RF showed deeper, more easily identifiable micropores versus low-energy microneedle RF.” On histology the researchers noted that tissue coagulation reached a depth of 1,500 mcm with high-energy microneedle RF, but low-energy microneedle RF only showed visible damage to the epidermis. “This also supports the idea that microneedles alone without energy do not reach the deeper layers of the dermis,” she said.

Dr. DiGiorgio concluded her presentation by discussing promising results from a split-face study of fractional microneedling RF for the treatment of rosacea. For the 12-week randomized study, researchers from South Korea performed two sessions 4 weeks apart, with no treatment to the control side. Erythema decreased 13.6% and results were maintained for about 2 months after treatment. The researchers also measured inflammatory markers and noticed decreased dermal inflammation and mast cell counts and decreased markers related to angiogenesis, inflammation, innate immunity, and neuronal cation channels. “This could be a promising treatment for inflammatory rosacea in the future,” Dr. DiGiorgio said.

She disclosed that she is a consultant for Allergan Aesthetics.

[email protected]

A limited number of high-quality studies demonstrate the efficacy of microneedling, but it’s a good alternative to lasers, especially for darker skin types, according to Catherine M. DiGiorgio, MD, MS.

During a virtual course on laser and aesthetic skin therapy, Dr. DiGiorgio, a laser and cosmetic dermatologist at the Boston Center for Facial Rejuvenation, provided a state-of-the-art update on microneedling, a procedure in which microneedles are rolled over the skin to create epidermal and dermal microwounds.

“The depths are adjustable and it’s purely mechanical: no energy is being delivered with these treatments,” she said. “The hypothesized mechanism of action is that microneedling creates microwounds which initiate wound healing to stimulate new collagen production. This breaks apart compact collagen in the superficial dermis while stimulating new collagen and elastin,” she explained, adding that it is also hypothesized that this “stimulates growth factors that directly impact collagen and elastin synthesis.”

Conditions that have been reported to be treatable with microneedling in the medical literature include scars – especially acne scars – as well as rhytides, skin laxity, striae, melasma, and enlarged pores. Microneedling can also be used for transdermal drug delivery, although it’s far inferior to microinjection of medications. Contraindications are similar to those with laser surgery, including active infection of the area, history of keloids, inflammatory acne, and immunosuppression; and it should not be performed on the same day as neuromodulator treatment, to avoid diffusion of the neuromodulator. Herpes simplex virus prophylaxis is also indicated prior to microneedling treatment.

Many devices are available for use, including fixed, manual needle rollers and electric-powered pens with single-use sterile cartridges. The devices vary by needle length, quantity, diameter, configuration, and material of which the microneedles are made of. The needle length is not reliable for penetration depth, especially when greater than 1 mm. Treatment guidelines vary based on the area being treated.

“You put tension on the skin and apply the device perpendicularly,” Dr. DiGiorgio said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “It should be performed in quadrants, and I prefer to treat in cosmetic units. The endpoint is pinpoint bleeding versus deep purpura. Ice water–soaked sterile gauze can be applied after treatment and skin care can be resumed in 5-7 days.”

In an effort to compare the efficacy and safety of the 2940-nm Er:YAG laser and microneedling for the treatment of atrophic acne scars, researchers in Egypt performed a randomized, split-face study in 30 patients. Study participants were evaluated by two blinded physicians at baseline and at 3 months follow-up. Both modalities showed a significant improvement in acne scars, but those treated with the Er:YAG laser showed a statistically significant greater improvement (70% vs. 30%, respectively; P < .001). Histology revealed a significantly higher increase in the mean quantity of collagen fibers in the Er:YAG-treated patients, compared with those who underwent microneedling, but patients in the microneedling group experienced less erythema and edema. Pain scores were significantly higher in the microneedling group compared with the Er:YAG group.

In a more recent study, researchers performed a systematic review of 37 articles in the medical literature related to microneedling. They found that the procedure provides good results when used on its own, and is preferred by patients because of its minimal downtime and side effects. However, they concluded that, while microneedling is a safe and effective option, methodological shortcomings and further research is required to establish it as an evidence-based therapeutic option.

“There are a limited number of high-quality studies demonstrating the efficacy of microneedling,” Dr. DiGiorgio said. “It is a safe procedure, which could complement laser treatments, so you could perform it between expensive and high-downtime lasers. It is an option for patients who seek measurable results with little to no downtime, and it’s also an option for clinicians who do not use laser-resurfacing devices. Basically, further research is needed to establish microneedling as an evidence-based therapeutic option. Laser continues to remain the gold standard for treatment.”

Another treatment option is fractional microneedling with radiofrequency (RF). These are microneedles which deliver energy in the form of RF at the tip of the needle, which denatures collagen and creates thermal coagulative injury zones at temperatures greater than 65° C. The microneedles can be insulated or noninsulated. “Insulated tips are safer for darker skin types because the epidermis is protected from the heat damage,” Dr. DiGiorgio said.

These treatments are used for the improvement of rhytides and scars and for skin tightening. “The treatments are painful and require topical anesthesia,” she said. “Erythema can range from about 24 hours to 4 days depending on the device being used. Usually monthly treatments are recommended.”

A study by investigators in South Korea and China set out to analyze histometric changes of this approach in pigs. They treated the pigs with a fractional microneedle delivery system at various depths, conduction times, and energies, and performed punch biopsies immediately after treatment, 4 days post treatment, and at 2 weeks post treatment. They noted that depth and conduction time affected the height, width, and volume of the columns of coagulation, but that the energy only affected the level of tissue destruction. “They also noted that RF-induced coagulated columns had a mixed cellular infiltrate, neovascularization, granular tissue formation with fibroblasts, and neocollagenesis and elastogenesis in the dermis,” Dr. DiGiorgio said.

In another study, researchers in Thailand performed a study in two women who were going to undergo abdominoplasty. Participants received six treatments prior to abdominoplasty with biopsies at different time intervals following microneedling with radiofrequency. The researchers tested five energy levels and five test areas; no collagen denaturization was observed with microneedling alone.

“This supports the idea that heat is required to stimulate neocollagenesis, and needles alone do not denature collagen,” Dr. DiGiorgio said. “They also found that neocollagenesis and neoelastogenesis occurred at optimal heating levels.”

In a separate study, researchers from Denmark used a number of different imaging modalities to evaluate the impact of microneedle fractional RF-induced micropores. When they used reflectance confocal microscopy, they observed that the micropores showed a concentric shape. “They contained hyper-reflective granules, and the coagulated tissue was seen from the epidermis to the dermal-epidermal junction,” Dr. DiGiorgio said. “This was not seen in the low energy microneedle RF. On optical coherence tomography, they noted that high-energy needle RF showed deeper, more easily identifiable micropores versus low-energy microneedle RF.” On histology the researchers noted that tissue coagulation reached a depth of 1,500 mcm with high-energy microneedle RF, but low-energy microneedle RF only showed visible damage to the epidermis. “This also supports the idea that microneedles alone without energy do not reach the deeper layers of the dermis,” she said.

Dr. DiGiorgio concluded her presentation by discussing promising results from a split-face study of fractional microneedling RF for the treatment of rosacea. For the 12-week randomized study, researchers from South Korea performed two sessions 4 weeks apart, with no treatment to the control side. Erythema decreased 13.6% and results were maintained for about 2 months after treatment. The researchers also measured inflammatory markers and noticed decreased dermal inflammation and mast cell counts and decreased markers related to angiogenesis, inflammation, innate immunity, and neuronal cation channels. “This could be a promising treatment for inflammatory rosacea in the future,” Dr. DiGiorgio said.

She disclosed that she is a consultant for Allergan Aesthetics.

[email protected]

A limited number of high-quality studies demonstrate the efficacy of microneedling, but it’s a good alternative to lasers, especially for darker skin types, according to Catherine M. DiGiorgio, MD, MS.

During a virtual course on laser and aesthetic skin therapy, Dr. DiGiorgio, a laser and cosmetic dermatologist at the Boston Center for Facial Rejuvenation, provided a state-of-the-art update on microneedling, a procedure in which microneedles are rolled over the skin to create epidermal and dermal microwounds.

“The depths are adjustable and it’s purely mechanical: no energy is being delivered with these treatments,” she said. “The hypothesized mechanism of action is that microneedling creates microwounds which initiate wound healing to stimulate new collagen production. This breaks apart compact collagen in the superficial dermis while stimulating new collagen and elastin,” she explained, adding that it is also hypothesized that this “stimulates growth factors that directly impact collagen and elastin synthesis.”

Conditions that have been reported to be treatable with microneedling in the medical literature include scars – especially acne scars – as well as rhytides, skin laxity, striae, melasma, and enlarged pores. Microneedling can also be used for transdermal drug delivery, although it’s far inferior to microinjection of medications. Contraindications are similar to those with laser surgery, including active infection of the area, history of keloids, inflammatory acne, and immunosuppression; and it should not be performed on the same day as neuromodulator treatment, to avoid diffusion of the neuromodulator. Herpes simplex virus prophylaxis is also indicated prior to microneedling treatment.

Many devices are available for use, including fixed, manual needle rollers and electric-powered pens with single-use sterile cartridges. The devices vary by needle length, quantity, diameter, configuration, and material of which the microneedles are made of. The needle length is not reliable for penetration depth, especially when greater than 1 mm. Treatment guidelines vary based on the area being treated.

“You put tension on the skin and apply the device perpendicularly,” Dr. DiGiorgio said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “It should be performed in quadrants, and I prefer to treat in cosmetic units. The endpoint is pinpoint bleeding versus deep purpura. Ice water–soaked sterile gauze can be applied after treatment and skin care can be resumed in 5-7 days.”

In an effort to compare the efficacy and safety of the 2940-nm Er:YAG laser and microneedling for the treatment of atrophic acne scars, researchers in Egypt performed a randomized, split-face study in 30 patients. Study participants were evaluated by two blinded physicians at baseline and at 3 months follow-up. Both modalities showed a significant improvement in acne scars, but those treated with the Er:YAG laser showed a statistically significant greater improvement (70% vs. 30%, respectively; P < .001). Histology revealed a significantly higher increase in the mean quantity of collagen fibers in the Er:YAG-treated patients, compared with those who underwent microneedling, but patients in the microneedling group experienced less erythema and edema. Pain scores were significantly higher in the microneedling group compared with the Er:YAG group.

In a more recent study, researchers performed a systematic review of 37 articles in the medical literature related to microneedling. They found that the procedure provides good results when used on its own, and is preferred by patients because of its minimal downtime and side effects. However, they concluded that, while microneedling is a safe and effective option, methodological shortcomings and further research is required to establish it as an evidence-based therapeutic option.

“There are a limited number of high-quality studies demonstrating the efficacy of microneedling,” Dr. DiGiorgio said. “It is a safe procedure, which could complement laser treatments, so you could perform it between expensive and high-downtime lasers. It is an option for patients who seek measurable results with little to no downtime, and it’s also an option for clinicians who do not use laser-resurfacing devices. Basically, further research is needed to establish microneedling as an evidence-based therapeutic option. Laser continues to remain the gold standard for treatment.”

Another treatment option is fractional microneedling with radiofrequency (RF). These are microneedles which deliver energy in the form of RF at the tip of the needle, which denatures collagen and creates thermal coagulative injury zones at temperatures greater than 65° C. The microneedles can be insulated or noninsulated. “Insulated tips are safer for darker skin types because the epidermis is protected from the heat damage,” Dr. DiGiorgio said.

These treatments are used for the improvement of rhytides and scars and for skin tightening. “The treatments are painful and require topical anesthesia,” she said. “Erythema can range from about 24 hours to 4 days depending on the device being used. Usually monthly treatments are recommended.”

A study by investigators in South Korea and China set out to analyze histometric changes of this approach in pigs. They treated the pigs with a fractional microneedle delivery system at various depths, conduction times, and energies, and performed punch biopsies immediately after treatment, 4 days post treatment, and at 2 weeks post treatment. They noted that depth and conduction time affected the height, width, and volume of the columns of coagulation, but that the energy only affected the level of tissue destruction. “They also noted that RF-induced coagulated columns had a mixed cellular infiltrate, neovascularization, granular tissue formation with fibroblasts, and neocollagenesis and elastogenesis in the dermis,” Dr. DiGiorgio said.

In another study, researchers in Thailand performed a study in two women who were going to undergo abdominoplasty. Participants received six treatments prior to abdominoplasty with biopsies at different time intervals following microneedling with radiofrequency. The researchers tested five energy levels and five test areas; no collagen denaturization was observed with microneedling alone.

“This supports the idea that heat is required to stimulate neocollagenesis, and needles alone do not denature collagen,” Dr. DiGiorgio said. “They also found that neocollagenesis and neoelastogenesis occurred at optimal heating levels.”

In a separate study, researchers from Denmark used a number of different imaging modalities to evaluate the impact of microneedle fractional RF-induced micropores. When they used reflectance confocal microscopy, they observed that the micropores showed a concentric shape. “They contained hyper-reflective granules, and the coagulated tissue was seen from the epidermis to the dermal-epidermal junction,” Dr. DiGiorgio said. “This was not seen in the low energy microneedle RF. On optical coherence tomography, they noted that high-energy needle RF showed deeper, more easily identifiable micropores versus low-energy microneedle RF.” On histology the researchers noted that tissue coagulation reached a depth of 1,500 mcm with high-energy microneedle RF, but low-energy microneedle RF only showed visible damage to the epidermis. “This also supports the idea that microneedles alone without energy do not reach the deeper layers of the dermis,” she said.

Dr. DiGiorgio concluded her presentation by discussing promising results from a split-face study of fractional microneedling RF for the treatment of rosacea. For the 12-week randomized study, researchers from South Korea performed two sessions 4 weeks apart, with no treatment to the control side. Erythema decreased 13.6% and results were maintained for about 2 months after treatment. The researchers also measured inflammatory markers and noticed decreased dermal inflammation and mast cell counts and decreased markers related to angiogenesis, inflammation, innate immunity, and neuronal cation channels. “This could be a promising treatment for inflammatory rosacea in the future,” Dr. DiGiorgio said.

She disclosed that she is a consultant for Allergan Aesthetics.

[email protected]

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

Cigarettes are still the product of choice among U.S. adults who use tobacco, but the youngest adults are more likely to use e-cigarettes than any other product, according to data from the 2019 National Health Interview Survey.

Just under 21% of all adults (an estimated 50.6 million individuals) said they used tobacco products “every day” or “some days,” with cigarette use reported by the largest share of respondents (14.0%) and e-cigarettes next at 4.5%, Monica E. Cornelius, PhD, and associates said in the Morbidity and Mortality Weekly Report.

Among adults aged 18-24 years, however, e-cigarettes were used by 9.3% of respondents in 2019, compared with 8.0% who used cigarettes every day or some days. Current e-cigarette use was 6.4% in 25- to 44-year-olds and continued to diminish with increasing age, said Dr. Cornelius and associates at the Centers for Disease Control and Prevention’s National Center for Chronic Disease Prevention and Health Promotion.

Men were more likely than women to use e-cigarettes (5.5% vs. 3.5%), and to use any tobacco product (26.2% vs. 15.7%). Use of other products, including cigarettes (15.3% for men vs. 12.7% for women), followed the same pattern to varying degrees, the national survey data show.

“Differences in prevalence of tobacco use also were also seen across population groups, with higher prevalence among those with a [high school equivalency degree], American Indian/Alaska Natives, uninsured adults and adults with Medicaid, and [lesbian, gay, or bisexual] adults,” the investigators said.

Among those groups, overall tobacco use and cigarette use were highest in those with an equivalency degree (43.8%, 37.1%), while lesbian/gay/bisexual individuals had the highest prevalence of e-cigarette use at 11.5%, they reported.

“As part of a comprehensive approach” to reduce tobacco-related disease and death, Dr. Cornelius and associates suggested, “targeted interventions are also warranted to reach subpopulations with the highest prevalence of use, which might vary by tobacco product type.”

[email protected]

SOURCE: Cornelius ME et al. MMWR. 2020 Nov 20;69(46);1736-42.

Cigarettes are still the product of choice among U.S. adults who use tobacco, but the youngest adults are more likely to use e-cigarettes than any other product, according to data from the 2019 National Health Interview Survey.

Just under 21% of all adults (an estimated 50.6 million individuals) said they used tobacco products “every day” or “some days,” with cigarette use reported by the largest share of respondents (14.0%) and e-cigarettes next at 4.5%, Monica E. Cornelius, PhD, and associates said in the Morbidity and Mortality Weekly Report.

Among adults aged 18-24 years, however, e-cigarettes were used by 9.3% of respondents in 2019, compared with 8.0% who used cigarettes every day or some days. Current e-cigarette use was 6.4% in 25- to 44-year-olds and continued to diminish with increasing age, said Dr. Cornelius and associates at the Centers for Disease Control and Prevention’s National Center for Chronic Disease Prevention and Health Promotion.

Men were more likely than women to use e-cigarettes (5.5% vs. 3.5%), and to use any tobacco product (26.2% vs. 15.7%). Use of other products, including cigarettes (15.3% for men vs. 12.7% for women), followed the same pattern to varying degrees, the national survey data show.

“Differences in prevalence of tobacco use also were also seen across population groups, with higher prevalence among those with a [high school equivalency degree], American Indian/Alaska Natives, uninsured adults and adults with Medicaid, and [lesbian, gay, or bisexual] adults,” the investigators said.

Among those groups, overall tobacco use and cigarette use were highest in those with an equivalency degree (43.8%, 37.1%), while lesbian/gay/bisexual individuals had the highest prevalence of e-cigarette use at 11.5%, they reported.

“As part of a comprehensive approach” to reduce tobacco-related disease and death, Dr. Cornelius and associates suggested, “targeted interventions are also warranted to reach subpopulations with the highest prevalence of use, which might vary by tobacco product type.”

[email protected]

SOURCE: Cornelius ME et al. MMWR. 2020 Nov 20;69(46);1736-42.

Cigarettes are still the product of choice among U.S. adults who use tobacco, but the youngest adults are more likely to use e-cigarettes than any other product, according to data from the 2019 National Health Interview Survey.

Just under 21% of all adults (an estimated 50.6 million individuals) said they used tobacco products “every day” or “some days,” with cigarette use reported by the largest share of respondents (14.0%) and e-cigarettes next at 4.5%, Monica E. Cornelius, PhD, and associates said in the Morbidity and Mortality Weekly Report.

Among adults aged 18-24 years, however, e-cigarettes were used by 9.3% of respondents in 2019, compared with 8.0% who used cigarettes every day or some days. Current e-cigarette use was 6.4% in 25- to 44-year-olds and continued to diminish with increasing age, said Dr. Cornelius and associates at the Centers for Disease Control and Prevention’s National Center for Chronic Disease Prevention and Health Promotion.

Men were more likely than women to use e-cigarettes (5.5% vs. 3.5%), and to use any tobacco product (26.2% vs. 15.7%). Use of other products, including cigarettes (15.3% for men vs. 12.7% for women), followed the same pattern to varying degrees, the national survey data show.

“Differences in prevalence of tobacco use also were also seen across population groups, with higher prevalence among those with a [high school equivalency degree], American Indian/Alaska Natives, uninsured adults and adults with Medicaid, and [lesbian, gay, or bisexual] adults,” the investigators said.

Among those groups, overall tobacco use and cigarette use were highest in those with an equivalency degree (43.8%, 37.1%), while lesbian/gay/bisexual individuals had the highest prevalence of e-cigarette use at 11.5%, they reported.

“As part of a comprehensive approach” to reduce tobacco-related disease and death, Dr. Cornelius and associates suggested, “targeted interventions are also warranted to reach subpopulations with the highest prevalence of use, which might vary by tobacco product type.”

[email protected]

SOURCE: Cornelius ME et al. MMWR. 2020 Nov 20;69(46);1736-42.