SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

A version of this article first appeared on Medscape.com.

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

A version of this article first appeared on Medscape.com.

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

A version of this article first appeared on Medscape.com.

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

A version of this article first appeared on Medscape.com.

A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.
 

Expanding the viability window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.
 

History behind the procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).
 

Recipient had ‘near-zero’ chance to get a liver in time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Dr. Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interest.

A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.
 

Expanding the viability window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.
 

History behind the procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).
 

Recipient had ‘near-zero’ chance to get a liver in time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Dr. Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interest.

A poor-quality human liver, rejected by all transplant centers, was treated outside the body for 3 days using a perfusion machine that simulated some functions of the human body and has been successfully transplanted into a patient with advanced cirrhosis.

The 62-year-old patient rapidly returned to normal quality of life and at the 1-year follow-up had no signs of liver damage, such as rejection or bile duct injury, according to the report published in Nature Biotechnology.

The study team was led by Pierre-Alain Clavien, MD, PhD, with the department of surgery and transplantation, Swiss Hepato-Pancreato-Biliary and Transplant Center, University Hospital Zürich, and the Wyss Zürich Translational Center, ETH Zürich and University of Zürich.
 

Expanding the viability window

Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ’s viability drops quickly after that time.

“This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure,” the authors wrote.

The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine. Features of the machine, which mimics human body functions, include automated remote control of all key parameters. A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.

The team had to solve factors that limit viability for any solid organ outside the body over a few hours including hemolysis, hemodynamic stability, glucose control, pathologic glycogen deposition and perfusate quality and dilution.

Additionally, because the organ would be under machine perfusion for several days, the scientists also had to address pressure necrosis.
 

History behind the procedure

The process started in 2015 with the support of the Wyss Zürich Translational Center, with the goal of long-term ex situ machine perfusion of injured liver grafts.

As part of the agreement from the Swiss regulatory authority (the Federal Office of Public Health) the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver, and if the organ met a rigorous bar for viability.

On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who had an invasive abdominal desmoid fibromatosis associated with chronic intra-abdominal abscesses and recurrent sepsis episodes from multiresistant bacteria. The donor needed long-term multiple medications and parenteral nutrition. Additionally, there was a 4-cm tumor in segment 1 of the liver.

The liver was refused by all other centers, “primarily because it required diagnostic workup of the liver lesion, which was not immediately possible, and because of the ongoing sepsis in the donor with multiresistant microorganisms,” the authors wrote.

The team removed the liver, and the graft was connected to the Wyss perfusion device for normothermic (37 °C) ex situ perfusion after 4 hours of cold preservation.

A 62-year-old male potential recipient on the official national transplant list, had earlier agreed to be considered for receiving a graft preserved ex situ in the Wyss machine.

The patient was fully informed about the process and the presence of a benign lesion in the graft and accepted the transplantation procedure. The patient had advanced cirrhosis, severe portal hypertension, and multiple and recurrent hepatocellular carcinoma (HCC).
 

Recipient had ‘near-zero’ chance to get a liver in time

The authors wrote that the patient had “a near-zero chance to receive a graft in time.”

For patients with HCC in Switzerland, the wait for liver transplant is longer than a year and no living-donor options were available.

The transplant operation took 5 hours and 26 minutes and blood loss was limited (600 mL). No transfusion was required. The patient was extubated in the operating room, transferred to the ICU, and discharged 12 days later.

Because a biopsy showed no detectable liver injury or rejection, and based on previous evidence of lower immunogenicity in perfused livers and kidneys, the researchers chose a reduced immunosuppressive regimen with quickly tapering steroids. The steroids were completely discontinued 6 weeks after surgery.

The authors wrote: “In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where ‘close-to-perfect’ livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel.”

In a press release, the team said the next step is to assess the procedure in other patients in a multicenter study.

Dr. Clavien and several coauthors affiliated with ETH (the Swiss Federal Institute of Technology in Zürich) and the University of Zürich have applied for patents on this new perfusion technology. No other authors have any competing interest.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

A version of this article first appeared on Medscape.com.

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

A version of this article first appeared on Medscape.com.

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

A version of this article first appeared on Medscape.com.