Pediatrics

Increasingly popular alternative peripartum practices such as water immersion and nonseverance of the umbilical cord may increase the risk of infections in newborns, a new clinical report from the American Academy of Pediatrics found.

Another perinatal measure potentially raising infection risk was placentophagy, according to a review led by Dawn Nolt, MD, MPH, a professor of pediatric infectious diseases at Oregon Health & Science University, Portland.

“Awareness of emerging alternative peripartum and neonatal practices helps pediatricians provide counseling to families before birth and to appropriately evaluate and treat neonates who have been exposed to these practices,” Dr. Nolt and colleagues wrote online in Pediatrics.

Amid growing inquiries made from women seeking a positive and meaningful birth experience through alternative approaches as well as reports of possibly related illness in newborns, Dr. Nolt’s group reviewed observational studies, case series, and medical society guidance on the risks associated with seven alternative birthing practices.

Based on their summation, it was not possible to quantify the actual risk associated with any one practice. “But of the seven we reviewed, as an infectious disease pediatrician I would say the most discernible immediate risk is likely attached to nonseverance of the cord,” Dr. Nolt said in an interview. “Left attached, the tissue can potentially necrote and transfer bacteria directly to the child.”

The authors made the following recommendations:

• Water immersion for labor and delivery. While this can increase the comfort of the mother in the first stages of labor, the water can become contaminated and increase the infant’s exposure to water-borne pathogens such as Legionella and Pseudomonas. It is not recommended after the second stage of labor and if offered, requires rigorous prophylactic and infection-control measures. This practice has also been linked to aspiration, drowning, hyponatremia, cord rupture, and death.
• Vaginal seeding. The skin, noses, and mouths of infants born by cesarean section are inoculated with swabs of vaginal fluid in order to expose them to vaginal bacteria that positively influence the infant’s microbiome. Of no known benefit, this measure can expose newborns to microbes such as group B Streptococcus and herpes simplex virus. Infants born by C-section receiving vaginal seeding should be evaluated the same way as those delivered vaginally.
• Umbilical cord nonseverance. Colloquially known as lotus birth, this is another practice with no evidence of advantage but with the potential to raise the risk of neonatal sepsis owing to the presence of necrotic umbilical or placental tissue. Some parents may view the placenta as a spiritual entity and fail to recognize it may be contaminated with harmful pathogens. Any placenta and umbilical cord attached to a febrile or ill-seeming neonate should be immediately removed.
• Placentophagy. Proponents believe placental consumption has antidepressive, analgesic, galactogogic, and nutritional properties. But eating raw, cooked, or dehydrated afterbirth tissue – viewed by some as a spiritual event – can expose a neonate to flora from the mother’s genitourinary tract and other sources encountered during preparation. Placentophagy has been associated with a case of recurrent late-onset group B streptococcal sepsis in a newborn. Strict food-handling practices at the level for raw meat should be maintained.
• HBV vaccine deferral. Viewed as “a critical safety net in preventing HBV infection,” the birth dose of the hepatitis B virus vaccine should not be postponed except for medical reasons. An estimated 1,000 new perinatally acquired HBV cases occurred annually in the United States from 2000 to 2009.
• Deferral of ocular prophylaxis. While ocular prophylaxis with topical erythromycin protects against gonococcal ophthalmia neonatorum, particularly in infants of high-risk mothers, it is not effective against other common pathogens. Parents and health care providers have recently questioned the need for its routine application, with concerns including its limited range of effectiveness as well as antibiotic resistance and shortages. With adequate prenatal testing, the risk of this neonatal conjunctivitis is significantly reduced, and deferral of prophylaxis may be considered in low-risk situations although it may be mandated by state legislation.
• Delayed bathing. The practice of delaying the infant’s first bath until several hours after birth may have several benefits. These include the initiation and exclusivity of breastfeeding, decreased mother/child separation time and risk of hypothermia, and protection of the neonatal skin microbiome. It should be discouraged, however, in neonates exposed to active herpes simplex virus lesions or whose mothers have a known history of HIV infection.

When women inquire about alternative practices, physicians need to strike a diplomatic balance between respecting women’s wishes and the benefits they hope to gain and at the same time informing them of potential risks, Dr. Nolt said. “The conversation we want to have with them should show compassion and sympathy but also tell them what the medical literature shows.” Patient and doctor should engage in shared decision-making about the safety of various alternative approaches.

“Over the last decade information on a variety of birth practices have become more widely available through social media and other Internet forums, which certainly has increased the variety of questions to health professionals, Amy C. Hermesch, MD, PhD, director of obstetric services at OHSC, said in an interview.

“We counsel about rare but serious risk, as noted in Dr. Nolt’s article,” said Dr. Hermesch, who was not involved in the AAP report. Most important is a discussion about appropriate pregnancy risk stratification. “For example, persons considering water immersion birth, probably the most common one I get inquiries about, should have an otherwise uncomplicated pregnancy with good mobility to get in and out of tub in the event of an emergency.”

While adverse events can happen during any birth, she sees these more often in mothers who underestimate the risk level of their situation or pregnancy when declining provider-recommended interventions. “I encourage pregnant persons to find a health care professional they trust who is knowledgeable about the benefits and the risk of all birth environments and interventions.”

Dr. Hermesch added that most alternative practices have little data to guide decisions, so she offers professional society recommendations, evidence review, and her own professional experiences. “The patient must weight the risk and benefits in the context of their value system and sometimes this means not following my advice or recommendations. My medical recommendation with the best of intentions does not remove patient autonomy.”

This report had no external funding. The authors had no potential conflicts of interest to disclose. Dr. Hermesch had no competing interests to declare.

Increasingly popular alternative peripartum practices such as water immersion and nonseverance of the umbilical cord may increase the risk of infections in newborns, a new clinical report from the American Academy of Pediatrics found.

Another perinatal measure potentially raising infection risk was placentophagy, according to a review led by Dawn Nolt, MD, MPH, a professor of pediatric infectious diseases at Oregon Health & Science University, Portland.

“Awareness of emerging alternative peripartum and neonatal practices helps pediatricians provide counseling to families before birth and to appropriately evaluate and treat neonates who have been exposed to these practices,” Dr. Nolt and colleagues wrote online in Pediatrics.

Amid growing inquiries made from women seeking a positive and meaningful birth experience through alternative approaches as well as reports of possibly related illness in newborns, Dr. Nolt’s group reviewed observational studies, case series, and medical society guidance on the risks associated with seven alternative birthing practices.

Based on their summation, it was not possible to quantify the actual risk associated with any one practice. “But of the seven we reviewed, as an infectious disease pediatrician I would say the most discernible immediate risk is likely attached to nonseverance of the cord,” Dr. Nolt said in an interview. “Left attached, the tissue can potentially necrote and transfer bacteria directly to the child.”

The authors made the following recommendations:

• Water immersion for labor and delivery. While this can increase the comfort of the mother in the first stages of labor, the water can become contaminated and increase the infant’s exposure to water-borne pathogens such as Legionella and Pseudomonas. It is not recommended after the second stage of labor and if offered, requires rigorous prophylactic and infection-control measures. This practice has also been linked to aspiration, drowning, hyponatremia, cord rupture, and death.
• Vaginal seeding. The skin, noses, and mouths of infants born by cesarean section are inoculated with swabs of vaginal fluid in order to expose them to vaginal bacteria that positively influence the infant’s microbiome. Of no known benefit, this measure can expose newborns to microbes such as group B Streptococcus and herpes simplex virus. Infants born by C-section receiving vaginal seeding should be evaluated the same way as those delivered vaginally.
• Umbilical cord nonseverance. Colloquially known as lotus birth, this is another practice with no evidence of advantage but with the potential to raise the risk of neonatal sepsis owing to the presence of necrotic umbilical or placental tissue. Some parents may view the placenta as a spiritual entity and fail to recognize it may be contaminated with harmful pathogens. Any placenta and umbilical cord attached to a febrile or ill-seeming neonate should be immediately removed.
• Placentophagy. Proponents believe placental consumption has antidepressive, analgesic, galactogogic, and nutritional properties. But eating raw, cooked, or dehydrated afterbirth tissue – viewed by some as a spiritual event – can expose a neonate to flora from the mother’s genitourinary tract and other sources encountered during preparation. Placentophagy has been associated with a case of recurrent late-onset group B streptococcal sepsis in a newborn. Strict food-handling practices at the level for raw meat should be maintained.
• HBV vaccine deferral. Viewed as “a critical safety net in preventing HBV infection,” the birth dose of the hepatitis B virus vaccine should not be postponed except for medical reasons. An estimated 1,000 new perinatally acquired HBV cases occurred annually in the United States from 2000 to 2009.
• Deferral of ocular prophylaxis. While ocular prophylaxis with topical erythromycin protects against gonococcal ophthalmia neonatorum, particularly in infants of high-risk mothers, it is not effective against other common pathogens. Parents and health care providers have recently questioned the need for its routine application, with concerns including its limited range of effectiveness as well as antibiotic resistance and shortages. With adequate prenatal testing, the risk of this neonatal conjunctivitis is significantly reduced, and deferral of prophylaxis may be considered in low-risk situations although it may be mandated by state legislation.
• Delayed bathing. The practice of delaying the infant’s first bath until several hours after birth may have several benefits. These include the initiation and exclusivity of breastfeeding, decreased mother/child separation time and risk of hypothermia, and protection of the neonatal skin microbiome. It should be discouraged, however, in neonates exposed to active herpes simplex virus lesions or whose mothers have a known history of HIV infection.

When women inquire about alternative practices, physicians need to strike a diplomatic balance between respecting women’s wishes and the benefits they hope to gain and at the same time informing them of potential risks, Dr. Nolt said. “The conversation we want to have with them should show compassion and sympathy but also tell them what the medical literature shows.” Patient and doctor should engage in shared decision-making about the safety of various alternative approaches.

“Over the last decade information on a variety of birth practices have become more widely available through social media and other Internet forums, which certainly has increased the variety of questions to health professionals, Amy C. Hermesch, MD, PhD, director of obstetric services at OHSC, said in an interview.

“We counsel about rare but serious risk, as noted in Dr. Nolt’s article,” said Dr. Hermesch, who was not involved in the AAP report. Most important is a discussion about appropriate pregnancy risk stratification. “For example, persons considering water immersion birth, probably the most common one I get inquiries about, should have an otherwise uncomplicated pregnancy with good mobility to get in and out of tub in the event of an emergency.”

While adverse events can happen during any birth, she sees these more often in mothers who underestimate the risk level of their situation or pregnancy when declining provider-recommended interventions. “I encourage pregnant persons to find a health care professional they trust who is knowledgeable about the benefits and the risk of all birth environments and interventions.”

Dr. Hermesch added that most alternative practices have little data to guide decisions, so she offers professional society recommendations, evidence review, and her own professional experiences. “The patient must weight the risk and benefits in the context of their value system and sometimes this means not following my advice or recommendations. My medical recommendation with the best of intentions does not remove patient autonomy.”

This report had no external funding. The authors had no potential conflicts of interest to disclose. Dr. Hermesch had no competing interests to declare.

Increasingly popular alternative peripartum practices such as water immersion and nonseverance of the umbilical cord may increase the risk of infections in newborns, a new clinical report from the American Academy of Pediatrics found.

Another perinatal measure potentially raising infection risk was placentophagy, according to a review led by Dawn Nolt, MD, MPH, a professor of pediatric infectious diseases at Oregon Health & Science University, Portland.

“Awareness of emerging alternative peripartum and neonatal practices helps pediatricians provide counseling to families before birth and to appropriately evaluate and treat neonates who have been exposed to these practices,” Dr. Nolt and colleagues wrote online in Pediatrics.

Amid growing inquiries made from women seeking a positive and meaningful birth experience through alternative approaches as well as reports of possibly related illness in newborns, Dr. Nolt’s group reviewed observational studies, case series, and medical society guidance on the risks associated with seven alternative birthing practices.

Based on their summation, it was not possible to quantify the actual risk associated with any one practice. “But of the seven we reviewed, as an infectious disease pediatrician I would say the most discernible immediate risk is likely attached to nonseverance of the cord,” Dr. Nolt said in an interview. “Left attached, the tissue can potentially necrote and transfer bacteria directly to the child.”

The authors made the following recommendations:

• Water immersion for labor and delivery. While this can increase the comfort of the mother in the first stages of labor, the water can become contaminated and increase the infant’s exposure to water-borne pathogens such as Legionella and Pseudomonas. It is not recommended after the second stage of labor and if offered, requires rigorous prophylactic and infection-control measures. This practice has also been linked to aspiration, drowning, hyponatremia, cord rupture, and death.
• Vaginal seeding. The skin, noses, and mouths of infants born by cesarean section are inoculated with swabs of vaginal fluid in order to expose them to vaginal bacteria that positively influence the infant’s microbiome. Of no known benefit, this measure can expose newborns to microbes such as group B Streptococcus and herpes simplex virus. Infants born by C-section receiving vaginal seeding should be evaluated the same way as those delivered vaginally.
• Umbilical cord nonseverance. Colloquially known as lotus birth, this is another practice with no evidence of advantage but with the potential to raise the risk of neonatal sepsis owing to the presence of necrotic umbilical or placental tissue. Some parents may view the placenta as a spiritual entity and fail to recognize it may be contaminated with harmful pathogens. Any placenta and umbilical cord attached to a febrile or ill-seeming neonate should be immediately removed.
• Placentophagy. Proponents believe placental consumption has antidepressive, analgesic, galactogogic, and nutritional properties. But eating raw, cooked, or dehydrated afterbirth tissue – viewed by some as a spiritual event – can expose a neonate to flora from the mother’s genitourinary tract and other sources encountered during preparation. Placentophagy has been associated with a case of recurrent late-onset group B streptococcal sepsis in a newborn. Strict food-handling practices at the level for raw meat should be maintained.
• HBV vaccine deferral. Viewed as “a critical safety net in preventing HBV infection,” the birth dose of the hepatitis B virus vaccine should not be postponed except for medical reasons. An estimated 1,000 new perinatally acquired HBV cases occurred annually in the United States from 2000 to 2009.
• Deferral of ocular prophylaxis. While ocular prophylaxis with topical erythromycin protects against gonococcal ophthalmia neonatorum, particularly in infants of high-risk mothers, it is not effective against other common pathogens. Parents and health care providers have recently questioned the need for its routine application, with concerns including its limited range of effectiveness as well as antibiotic resistance and shortages. With adequate prenatal testing, the risk of this neonatal conjunctivitis is significantly reduced, and deferral of prophylaxis may be considered in low-risk situations although it may be mandated by state legislation.
• Delayed bathing. The practice of delaying the infant’s first bath until several hours after birth may have several benefits. These include the initiation and exclusivity of breastfeeding, decreased mother/child separation time and risk of hypothermia, and protection of the neonatal skin microbiome. It should be discouraged, however, in neonates exposed to active herpes simplex virus lesions or whose mothers have a known history of HIV infection.

When women inquire about alternative practices, physicians need to strike a diplomatic balance between respecting women’s wishes and the benefits they hope to gain and at the same time informing them of potential risks, Dr. Nolt said. “The conversation we want to have with them should show compassion and sympathy but also tell them what the medical literature shows.” Patient and doctor should engage in shared decision-making about the safety of various alternative approaches.

“Over the last decade information on a variety of birth practices have become more widely available through social media and other Internet forums, which certainly has increased the variety of questions to health professionals, Amy C. Hermesch, MD, PhD, director of obstetric services at OHSC, said in an interview.

“We counsel about rare but serious risk, as noted in Dr. Nolt’s article,” said Dr. Hermesch, who was not involved in the AAP report. Most important is a discussion about appropriate pregnancy risk stratification. “For example, persons considering water immersion birth, probably the most common one I get inquiries about, should have an otherwise uncomplicated pregnancy with good mobility to get in and out of tub in the event of an emergency.”

While adverse events can happen during any birth, she sees these more often in mothers who underestimate the risk level of their situation or pregnancy when declining provider-recommended interventions. “I encourage pregnant persons to find a health care professional they trust who is knowledgeable about the benefits and the risk of all birth environments and interventions.”

Dr. Hermesch added that most alternative practices have little data to guide decisions, so she offers professional society recommendations, evidence review, and her own professional experiences. “The patient must weight the risk and benefits in the context of their value system and sometimes this means not following my advice or recommendations. My medical recommendation with the best of intentions does not remove patient autonomy.”

This report had no external funding. The authors had no potential conflicts of interest to disclose. Dr. Hermesch had no competing interests to declare.

“No one has asked young people what they want,” said Tabitha Randell, MBChB, an endocrinologist with Nottingham (England) University Hospitals NHS Trust, who specializes in treating teenagers with type 1 diabetes as they transition to adult care.

Dr. Randell, who has set up a very successful specialist service in her hospital for such patients, said: “We consistently have the best, or the second best, outcomes in this country for our diabetes patients.” She believes this is one of the most important issues in modern endocrinology today.

Speaking at the Diabetes Professional Care conference in London at the end of 2021, and sharing her thoughts afterward with this news organization, she noted that in general there are “virtually no published outcomes” on how best to transition a patient with type 1 diabetes from pediatric to adult care.

“If you actually get them to transition – because some just drop out and disengage and there’s nothing you can do – none of them get lost. Some of them disengage in the adult clinic, but if you’re in the young diabetes service [in England] the rules are that if you miss a diabetes appointment you do not get discharged, as compared with the adult clinic, where if you miss an appointment, you are discharged.”

In the young diabetes clinic, doctors will “carry on trying to contact you, and get you back,” she explained. “And the patients do eventually come back in – it might be a year or 2, but they do come back. We’ve just got to keep them alive in the meantime!”

This issue needs tackling all over the world. Dr. Randell said she’s not aware of any one country – although there may be “pockets” of good care within a given country – that is doing this perfectly.

Across the pond, Grazia Aleppo, MD, division of endocrinology at Northwestern University, Chicago, agreed that transitioning pediatric patients with type 1 diabetes to adult care presents “unique challenges.”
 

Challenges when transitioning from pediatric to adult care

During childhood, type 1 diabetes management is largely supervised by patients’ parents and members of the pediatric diabetes care team, which may include diabetes educators, psychologists, or social workers, as well as pediatric endocrinologists.

When the patient with type 1 diabetes becomes a young adult and takes over management of their own health, Dr. Aleppo said, the care team may diminish along with the time spent in provider visits.

The adult endocrinology setting focuses more on self-management and autonomous functioning of the individual with diabetes.

Adult appointments are typically shorter, and the patient is usually expected to follow doctors’ suggestions independently, she noted. They are also expected to manage the practical aspects of their diabetes care, including prescriptions, diabetes supplies, laboratory tests, scheduling, and keeping appointments.

At the same time that the emerging adult needs to start asserting independence over their health care, they will also be going through a myriad of other important lifestyle changes, such as attending college, living on their own for the first time, and starting a career.  

“With these fundamental differences and challenges, competing priorities, such as college, work and relationships, medical care may become of secondary importance and patients may become disengaged,” Dr. Aleppo explained.

As Dr. Randell has said, loss to follow-up is a big problem with this patient population, with disengagement from specialist services and worsening A1c across the transition, Dr. Aleppo noted. This makes addressing these patients’ specific needs extremely important.
 

Engage with kid, not disease; don’t palm them off on new recruits

“The really key thing these kids say is, ‘I do not want to be a disease,’” Dr. Randell said. “They want you to know that they are a person. Engage these kids!” she suggested. “Ask them: ‘How is your exam revision going?’ Find something positive to say, even if it’s just: ‘I’m glad you came today.’ ”

“If the first thing that you do is tell them off [for poor diabetes care], you are never going to see them again,” she cautioned.

Dr. Randell also said that role models with type 1 diabetes, such as Lila Moss – daughter of British supermodel Kate Moss – who was recently pictured wearing an insulin pump on her leg on the catwalk, are helping youngsters not feel so self-conscious about their diabetes.

“Let them know it’s not the end of the world, having [type 1] diabetes,” she emphasized.  

And Partha Kar, MBBS, OBE, national specialty advisor, diabetes with NHS England, agreed wholeheartedly with Dr. Randall.

Reminiscing about his early days as a newly qualified endocrinologist, Dr. Kar, who works at Portsmouth (England) Hospital NHS Trust, noted that as a new member of staff he was given the youth with type 1 diabetes – those getting ready to transition to adult care – to look after.

But this is the exact opposite of what should be happening, he emphasized. “If you don’t think transition care is important, you shouldn’t be treating type 1 diabetes.”

He believes that every diabetes center “must have a young-adult team lead” and this job must not be given to the least experienced member of staff.

This lead “doesn’t need to be a doctor,” Dr. Kar stressed. “It can be a psychologist, or a diabetes nurse, or a pharmacist, or a dietician.”

In short, it must be someone experienced who loves working with this age group.  

Dr. Randell agreed: “Make sure the team is interested in young people. It shouldn’t be the last person in who gets the job no one else wants.” Teens “are my favorite group to work with. They don’t take any nonsense.”

And she explained: “Young people like to get to know the person who’s going to take care of them. So, stay with them for their young adult years.” This can be “quite a fluid period,” with it normally extending to age 25, but in some cases, “it can be up to 32 years old.”
 

Preparing for the transition

To ease pediatric patients into the transition to adult care, Dr. Aleppo recommended that the pediatric diabetes team provide enough time so that any concerns the patient and their family may have can be addressed.

This should also include transferring management responsibilities to the young adult rather than their parent.

The pediatric provider should discuss with the patient available potential adult colleagues, personalizing these options to their needs, she said.

And the adult and pediatric clinicians should collaborate and provide important information beyond medical records or health summaries.

Adult providers should guide young adults on how to navigate the new practices, from scheduling follow-up appointments to policies regarding medication refills or supplies, to providing information about urgent numbers or email addresses for after-hours communications.

Dr. Kar reiterated that there are too few published outcomes in this patient group to guide the establishment of good transition services.

“Without data, we are dead on the ground. Without data, it’s all conjecture, anecdotes,” he said.

What he does know is that, in the latest national type 1 diabetes audit for England, “Diabetic ketoacidosis admissions ... are up in this age group,” which suggests these patients are not receiving adequate care.
 

Be a guide, not a gatekeeper

Dr. Kar stressed that, of the 8,760 hours in a year, the average patient with type 1 diabetes in the United Kingdom gets just “1-2 hours with you as a clinician, based on four appointments per year of 30 minutes each.”

“So you spend 0.02% of their time with individuals with type 1 diabetes. So, what’s the one thing you can do with that minimal contact? Be nice!”

Dr. Kar said he always has his email open to his adult patients and they are very respectful of his time. “They don’t email you at 1 a.m. That means every one of my patients has got support [from me]. Don’t be a barrier.”

“We have to fundamentally change the narrative. Doctors must have more empathy,” he said, stating that the one thing adolescents have constantly given feedback on has been, “Why don’t appointments start with: ‘How are you?’ 

“For a teenager, if you throw type 1 diabetes into the loop, it’s not easy,” he stressed. “Talk to them about something else. As a clinician, be a guide, not a gatekeeper. Give people the tools to self-manage better.”

Adult providers can meet these young adult patients “at their level,” Dr. Aleppo agreed.

“Pay attention to their immediate needs and focus on their present circumstances – whether how to get through their next semester in college, navigating job interviews, or handling having diabetes in the workplace.”

Paying attention to the mental health needs of these young patients is equally “paramount,” Dr. Aleppo said.

While access to mental health professionals may be challenging in the adult setting, providers should bring it up with their patients and offer counseling referrals.

“Diabetes impacts everything, and office appointments and conversations carry weight on these patients’ lives as a whole, not just on their diabetes,” she stressed. “A patient told me recently: ‘We’re learning to be adults,’ which can be hard enough, and with diabetes it can be even more challenging. Adult providers need to be aware of the patient’s ‘diabetes language’ in that often it is not what a patient is saying, rather how they are saying it that gives us information on what they truly need.

“As adult providers, we need to also train and teach our young patients to advocate for themselves on where to find resources that can help them navigate adulthood with diabetes,” she added.

One particularly helpful resource in the United States is the College Diabetes Network, a not-for-profit organization whose mission is to equip young adults with type 1 diabetes to successfully manage the challenging transition to independence at college and beyond.

“The sweetest thing that can happen to us as adult diabetes providers is when a patient – seen as an emerging adult during college – returns to your practice 10 years later after moving back and seeks you out for their diabetes care because of the relationship and trust you developed in those transitioning years,” Dr. Aleppo said.

Another resource is a freely available comic book series cocreated by Dr. Kar and colleague Mayank Patel, MBBS, an endocrinologist from University Hospital Southampton NHS Foundation Trust.

As detailed by this news organization in 2021, the series consists of three volumes: the first, Type 1: Origins, focuses on actual experiences of patients who have type 1 diabetes; the second, Type 1: Attack of the Ketones, is aimed at professionals who may provide care but have limited understanding of type 1 diabetes; and the third, Type 1 Mission 3: S.T.I.G.M.A., addresses the stigmas and misconceptions that patients with type 1 diabetes may face.

The idea for the first comic was inspired by a patient who compared having diabetes to being like the Marvel character The Hulk, said Dr. Kar, and has been expanded to include the additional volumes.

Dr. Kar and Dr. Patel have also just launched the fourth comic in the series, Type 1: Generations, to mark the 100-year anniversary since insulin was first given to a human.
 

“This is high priority”  

Dr. Kar said the NHS in England has just appointed a national lead for type 1 diabetes in youth, Fulya Mehta, MD, of Alder Hey Children’s NHS Foundation Trust, Liverpool, England.

“If you have a plan, bring it to us,” he told the audience at the DPC conference, and “tell us, what is the one thing you would change? This is not a session we are doing just to tick a box. This is high priority.

“Encourage your colleagues to think about transition services. This is an absolute priority. We will be asking every center [in England] who is your transitioning lead?”

And he once again stressed that “a lead of transition service does not have to be a medic. This should be a multidisciplinary team. But they do need to be comfortable in that space. To that teenager, your job title means nothing. Give them time and space.”

Dr. Randell summed it up: “If we can work together, it’s only going to result in better outcomes. We need to blaze the trail for young people.”

Dr. Aleppo has reported serving as a consultant to Dexcom and Insulet and receiving support to Northwestern University from AstraZeneca, Dexcom, Eli Lilly, Fractyl Health, Insulet, and Novo Nordisk. Dr. Randell and Dr. Kar have no conflicts of interest.

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

“No one has asked young people what they want,” said Tabitha Randell, MBChB, an endocrinologist with Nottingham (England) University Hospitals NHS Trust, who specializes in treating teenagers with type 1 diabetes as they transition to adult care.

Dr. Randell, who has set up a very successful specialist service in her hospital for such patients, said: “We consistently have the best, or the second best, outcomes in this country for our diabetes patients.” She believes this is one of the most important issues in modern endocrinology today.

Speaking at the Diabetes Professional Care conference in London at the end of 2021, and sharing her thoughts afterward with this news organization, she noted that in general there are “virtually no published outcomes” on how best to transition a patient with type 1 diabetes from pediatric to adult care.

“If you actually get them to transition – because some just drop out and disengage and there’s nothing you can do – none of them get lost. Some of them disengage in the adult clinic, but if you’re in the young diabetes service [in England] the rules are that if you miss a diabetes appointment you do not get discharged, as compared with the adult clinic, where if you miss an appointment, you are discharged.”

In the young diabetes clinic, doctors will “carry on trying to contact you, and get you back,” she explained. “And the patients do eventually come back in – it might be a year or 2, but they do come back. We’ve just got to keep them alive in the meantime!”

This issue needs tackling all over the world. Dr. Randell said she’s not aware of any one country – although there may be “pockets” of good care within a given country – that is doing this perfectly.

Across the pond, Grazia Aleppo, MD, division of endocrinology at Northwestern University, Chicago, agreed that transitioning pediatric patients with type 1 diabetes to adult care presents “unique challenges.”
 

Challenges when transitioning from pediatric to adult care

During childhood, type 1 diabetes management is largely supervised by patients’ parents and members of the pediatric diabetes care team, which may include diabetes educators, psychologists, or social workers, as well as pediatric endocrinologists.

When the patient with type 1 diabetes becomes a young adult and takes over management of their own health, Dr. Aleppo said, the care team may diminish along with the time spent in provider visits.

The adult endocrinology setting focuses more on self-management and autonomous functioning of the individual with diabetes.

Adult appointments are typically shorter, and the patient is usually expected to follow doctors’ suggestions independently, she noted. They are also expected to manage the practical aspects of their diabetes care, including prescriptions, diabetes supplies, laboratory tests, scheduling, and keeping appointments.

At the same time that the emerging adult needs to start asserting independence over their health care, they will also be going through a myriad of other important lifestyle changes, such as attending college, living on their own for the first time, and starting a career.  

“With these fundamental differences and challenges, competing priorities, such as college, work and relationships, medical care may become of secondary importance and patients may become disengaged,” Dr. Aleppo explained.

As Dr. Randell has said, loss to follow-up is a big problem with this patient population, with disengagement from specialist services and worsening A1c across the transition, Dr. Aleppo noted. This makes addressing these patients’ specific needs extremely important.
 

Engage with kid, not disease; don’t palm them off on new recruits

“The really key thing these kids say is, ‘I do not want to be a disease,’” Dr. Randell said. “They want you to know that they are a person. Engage these kids!” she suggested. “Ask them: ‘How is your exam revision going?’ Find something positive to say, even if it’s just: ‘I’m glad you came today.’ ”

“If the first thing that you do is tell them off [for poor diabetes care], you are never going to see them again,” she cautioned.

Dr. Randell also said that role models with type 1 diabetes, such as Lila Moss – daughter of British supermodel Kate Moss – who was recently pictured wearing an insulin pump on her leg on the catwalk, are helping youngsters not feel so self-conscious about their diabetes.

“Let them know it’s not the end of the world, having [type 1] diabetes,” she emphasized.  

And Partha Kar, MBBS, OBE, national specialty advisor, diabetes with NHS England, agreed wholeheartedly with Dr. Randall.

Reminiscing about his early days as a newly qualified endocrinologist, Dr. Kar, who works at Portsmouth (England) Hospital NHS Trust, noted that as a new member of staff he was given the youth with type 1 diabetes – those getting ready to transition to adult care – to look after.

But this is the exact opposite of what should be happening, he emphasized. “If you don’t think transition care is important, you shouldn’t be treating type 1 diabetes.”

He believes that every diabetes center “must have a young-adult team lead” and this job must not be given to the least experienced member of staff.

This lead “doesn’t need to be a doctor,” Dr. Kar stressed. “It can be a psychologist, or a diabetes nurse, or a pharmacist, or a dietician.”

In short, it must be someone experienced who loves working with this age group.  

Dr. Randell agreed: “Make sure the team is interested in young people. It shouldn’t be the last person in who gets the job no one else wants.” Teens “are my favorite group to work with. They don’t take any nonsense.”

And she explained: “Young people like to get to know the person who’s going to take care of them. So, stay with them for their young adult years.” This can be “quite a fluid period,” with it normally extending to age 25, but in some cases, “it can be up to 32 years old.”
 

Preparing for the transition

To ease pediatric patients into the transition to adult care, Dr. Aleppo recommended that the pediatric diabetes team provide enough time so that any concerns the patient and their family may have can be addressed.

This should also include transferring management responsibilities to the young adult rather than their parent.

The pediatric provider should discuss with the patient available potential adult colleagues, personalizing these options to their needs, she said.

And the adult and pediatric clinicians should collaborate and provide important information beyond medical records or health summaries.

Adult providers should guide young adults on how to navigate the new practices, from scheduling follow-up appointments to policies regarding medication refills or supplies, to providing information about urgent numbers or email addresses for after-hours communications.

Dr. Kar reiterated that there are too few published outcomes in this patient group to guide the establishment of good transition services.

“Without data, we are dead on the ground. Without data, it’s all conjecture, anecdotes,” he said.

What he does know is that, in the latest national type 1 diabetes audit for England, “Diabetic ketoacidosis admissions ... are up in this age group,” which suggests these patients are not receiving adequate care.
 

Be a guide, not a gatekeeper

Dr. Kar stressed that, of the 8,760 hours in a year, the average patient with type 1 diabetes in the United Kingdom gets just “1-2 hours with you as a clinician, based on four appointments per year of 30 minutes each.”

“So you spend 0.02% of their time with individuals with type 1 diabetes. So, what’s the one thing you can do with that minimal contact? Be nice!”

Dr. Kar said he always has his email open to his adult patients and they are very respectful of his time. “They don’t email you at 1 a.m. That means every one of my patients has got support [from me]. Don’t be a barrier.”

“We have to fundamentally change the narrative. Doctors must have more empathy,” he said, stating that the one thing adolescents have constantly given feedback on has been, “Why don’t appointments start with: ‘How are you?’ 

“For a teenager, if you throw type 1 diabetes into the loop, it’s not easy,” he stressed. “Talk to them about something else. As a clinician, be a guide, not a gatekeeper. Give people the tools to self-manage better.”

Adult providers can meet these young adult patients “at their level,” Dr. Aleppo agreed.

“Pay attention to their immediate needs and focus on their present circumstances – whether how to get through their next semester in college, navigating job interviews, or handling having diabetes in the workplace.”

Paying attention to the mental health needs of these young patients is equally “paramount,” Dr. Aleppo said.

While access to mental health professionals may be challenging in the adult setting, providers should bring it up with their patients and offer counseling referrals.

“Diabetes impacts everything, and office appointments and conversations carry weight on these patients’ lives as a whole, not just on their diabetes,” she stressed. “A patient told me recently: ‘We’re learning to be adults,’ which can be hard enough, and with diabetes it can be even more challenging. Adult providers need to be aware of the patient’s ‘diabetes language’ in that often it is not what a patient is saying, rather how they are saying it that gives us information on what they truly need.

“As adult providers, we need to also train and teach our young patients to advocate for themselves on where to find resources that can help them navigate adulthood with diabetes,” she added.

One particularly helpful resource in the United States is the College Diabetes Network, a not-for-profit organization whose mission is to equip young adults with type 1 diabetes to successfully manage the challenging transition to independence at college and beyond.

“The sweetest thing that can happen to us as adult diabetes providers is when a patient – seen as an emerging adult during college – returns to your practice 10 years later after moving back and seeks you out for their diabetes care because of the relationship and trust you developed in those transitioning years,” Dr. Aleppo said.

Another resource is a freely available comic book series cocreated by Dr. Kar and colleague Mayank Patel, MBBS, an endocrinologist from University Hospital Southampton NHS Foundation Trust.

As detailed by this news organization in 2021, the series consists of three volumes: the first, Type 1: Origins, focuses on actual experiences of patients who have type 1 diabetes; the second, Type 1: Attack of the Ketones, is aimed at professionals who may provide care but have limited understanding of type 1 diabetes; and the third, Type 1 Mission 3: S.T.I.G.M.A., addresses the stigmas and misconceptions that patients with type 1 diabetes may face.

The idea for the first comic was inspired by a patient who compared having diabetes to being like the Marvel character The Hulk, said Dr. Kar, and has been expanded to include the additional volumes.

Dr. Kar and Dr. Patel have also just launched the fourth comic in the series, Type 1: Generations, to mark the 100-year anniversary since insulin was first given to a human.
 

“This is high priority”  

Dr. Kar said the NHS in England has just appointed a national lead for type 1 diabetes in youth, Fulya Mehta, MD, of Alder Hey Children’s NHS Foundation Trust, Liverpool, England.

“If you have a plan, bring it to us,” he told the audience at the DPC conference, and “tell us, what is the one thing you would change? This is not a session we are doing just to tick a box. This is high priority.

“Encourage your colleagues to think about transition services. This is an absolute priority. We will be asking every center [in England] who is your transitioning lead?”

And he once again stressed that “a lead of transition service does not have to be a medic. This should be a multidisciplinary team. But they do need to be comfortable in that space. To that teenager, your job title means nothing. Give them time and space.”

Dr. Randell summed it up: “If we can work together, it’s only going to result in better outcomes. We need to blaze the trail for young people.”

Dr. Aleppo has reported serving as a consultant to Dexcom and Insulet and receiving support to Northwestern University from AstraZeneca, Dexcom, Eli Lilly, Fractyl Health, Insulet, and Novo Nordisk. Dr. Randell and Dr. Kar have no conflicts of interest.

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

“No one has asked young people what they want,” said Tabitha Randell, MBChB, an endocrinologist with Nottingham (England) University Hospitals NHS Trust, who specializes in treating teenagers with type 1 diabetes as they transition to adult care.

Dr. Randell, who has set up a very successful specialist service in her hospital for such patients, said: “We consistently have the best, or the second best, outcomes in this country for our diabetes patients.” She believes this is one of the most important issues in modern endocrinology today.

Speaking at the Diabetes Professional Care conference in London at the end of 2021, and sharing her thoughts afterward with this news organization, she noted that in general there are “virtually no published outcomes” on how best to transition a patient with type 1 diabetes from pediatric to adult care.

“If you actually get them to transition – because some just drop out and disengage and there’s nothing you can do – none of them get lost. Some of them disengage in the adult clinic, but if you’re in the young diabetes service [in England] the rules are that if you miss a diabetes appointment you do not get discharged, as compared with the adult clinic, where if you miss an appointment, you are discharged.”

In the young diabetes clinic, doctors will “carry on trying to contact you, and get you back,” she explained. “And the patients do eventually come back in – it might be a year or 2, but they do come back. We’ve just got to keep them alive in the meantime!”

This issue needs tackling all over the world. Dr. Randell said she’s not aware of any one country – although there may be “pockets” of good care within a given country – that is doing this perfectly.

Across the pond, Grazia Aleppo, MD, division of endocrinology at Northwestern University, Chicago, agreed that transitioning pediatric patients with type 1 diabetes to adult care presents “unique challenges.”
 

Challenges when transitioning from pediatric to adult care

During childhood, type 1 diabetes management is largely supervised by patients’ parents and members of the pediatric diabetes care team, which may include diabetes educators, psychologists, or social workers, as well as pediatric endocrinologists.

When the patient with type 1 diabetes becomes a young adult and takes over management of their own health, Dr. Aleppo said, the care team may diminish along with the time spent in provider visits.

The adult endocrinology setting focuses more on self-management and autonomous functioning of the individual with diabetes.

Adult appointments are typically shorter, and the patient is usually expected to follow doctors’ suggestions independently, she noted. They are also expected to manage the practical aspects of their diabetes care, including prescriptions, diabetes supplies, laboratory tests, scheduling, and keeping appointments.

At the same time that the emerging adult needs to start asserting independence over their health care, they will also be going through a myriad of other important lifestyle changes, such as attending college, living on their own for the first time, and starting a career.  

“With these fundamental differences and challenges, competing priorities, such as college, work and relationships, medical care may become of secondary importance and patients may become disengaged,” Dr. Aleppo explained.

As Dr. Randell has said, loss to follow-up is a big problem with this patient population, with disengagement from specialist services and worsening A1c across the transition, Dr. Aleppo noted. This makes addressing these patients’ specific needs extremely important.
 

Engage with kid, not disease; don’t palm them off on new recruits

“The really key thing these kids say is, ‘I do not want to be a disease,’” Dr. Randell said. “They want you to know that they are a person. Engage these kids!” she suggested. “Ask them: ‘How is your exam revision going?’ Find something positive to say, even if it’s just: ‘I’m glad you came today.’ ”

“If the first thing that you do is tell them off [for poor diabetes care], you are never going to see them again,” she cautioned.

Dr. Randell also said that role models with type 1 diabetes, such as Lila Moss – daughter of British supermodel Kate Moss – who was recently pictured wearing an insulin pump on her leg on the catwalk, are helping youngsters not feel so self-conscious about their diabetes.

“Let them know it’s not the end of the world, having [type 1] diabetes,” she emphasized.  

And Partha Kar, MBBS, OBE, national specialty advisor, diabetes with NHS England, agreed wholeheartedly with Dr. Randall.

Reminiscing about his early days as a newly qualified endocrinologist, Dr. Kar, who works at Portsmouth (England) Hospital NHS Trust, noted that as a new member of staff he was given the youth with type 1 diabetes – those getting ready to transition to adult care – to look after.

But this is the exact opposite of what should be happening, he emphasized. “If you don’t think transition care is important, you shouldn’t be treating type 1 diabetes.”

He believes that every diabetes center “must have a young-adult team lead” and this job must not be given to the least experienced member of staff.

This lead “doesn’t need to be a doctor,” Dr. Kar stressed. “It can be a psychologist, or a diabetes nurse, or a pharmacist, or a dietician.”

In short, it must be someone experienced who loves working with this age group.  

Dr. Randell agreed: “Make sure the team is interested in young people. It shouldn’t be the last person in who gets the job no one else wants.” Teens “are my favorite group to work with. They don’t take any nonsense.”

And she explained: “Young people like to get to know the person who’s going to take care of them. So, stay with them for their young adult years.” This can be “quite a fluid period,” with it normally extending to age 25, but in some cases, “it can be up to 32 years old.”
 

Preparing for the transition

To ease pediatric patients into the transition to adult care, Dr. Aleppo recommended that the pediatric diabetes team provide enough time so that any concerns the patient and their family may have can be addressed.

This should also include transferring management responsibilities to the young adult rather than their parent.

The pediatric provider should discuss with the patient available potential adult colleagues, personalizing these options to their needs, she said.

And the adult and pediatric clinicians should collaborate and provide important information beyond medical records or health summaries.

Adult providers should guide young adults on how to navigate the new practices, from scheduling follow-up appointments to policies regarding medication refills or supplies, to providing information about urgent numbers or email addresses for after-hours communications.

Dr. Kar reiterated that there are too few published outcomes in this patient group to guide the establishment of good transition services.

“Without data, we are dead on the ground. Without data, it’s all conjecture, anecdotes,” he said.

What he does know is that, in the latest national type 1 diabetes audit for England, “Diabetic ketoacidosis admissions ... are up in this age group,” which suggests these patients are not receiving adequate care.
 

Be a guide, not a gatekeeper

Dr. Kar stressed that, of the 8,760 hours in a year, the average patient with type 1 diabetes in the United Kingdom gets just “1-2 hours with you as a clinician, based on four appointments per year of 30 minutes each.”

“So you spend 0.02% of their time with individuals with type 1 diabetes. So, what’s the one thing you can do with that minimal contact? Be nice!”

Dr. Kar said he always has his email open to his adult patients and they are very respectful of his time. “They don’t email you at 1 a.m. That means every one of my patients has got support [from me]. Don’t be a barrier.”

“We have to fundamentally change the narrative. Doctors must have more empathy,” he said, stating that the one thing adolescents have constantly given feedback on has been, “Why don’t appointments start with: ‘How are you?’ 

“For a teenager, if you throw type 1 diabetes into the loop, it’s not easy,” he stressed. “Talk to them about something else. As a clinician, be a guide, not a gatekeeper. Give people the tools to self-manage better.”

Adult providers can meet these young adult patients “at their level,” Dr. Aleppo agreed.

“Pay attention to their immediate needs and focus on their present circumstances – whether how to get through their next semester in college, navigating job interviews, or handling having diabetes in the workplace.”

Paying attention to the mental health needs of these young patients is equally “paramount,” Dr. Aleppo said.

While access to mental health professionals may be challenging in the adult setting, providers should bring it up with their patients and offer counseling referrals.

“Diabetes impacts everything, and office appointments and conversations carry weight on these patients’ lives as a whole, not just on their diabetes,” she stressed. “A patient told me recently: ‘We’re learning to be adults,’ which can be hard enough, and with diabetes it can be even more challenging. Adult providers need to be aware of the patient’s ‘diabetes language’ in that often it is not what a patient is saying, rather how they are saying it that gives us information on what they truly need.

“As adult providers, we need to also train and teach our young patients to advocate for themselves on where to find resources that can help them navigate adulthood with diabetes,” she added.

One particularly helpful resource in the United States is the College Diabetes Network, a not-for-profit organization whose mission is to equip young adults with type 1 diabetes to successfully manage the challenging transition to independence at college and beyond.

“The sweetest thing that can happen to us as adult diabetes providers is when a patient – seen as an emerging adult during college – returns to your practice 10 years later after moving back and seeks you out for their diabetes care because of the relationship and trust you developed in those transitioning years,” Dr. Aleppo said.

Another resource is a freely available comic book series cocreated by Dr. Kar and colleague Mayank Patel, MBBS, an endocrinologist from University Hospital Southampton NHS Foundation Trust.

As detailed by this news organization in 2021, the series consists of three volumes: the first, Type 1: Origins, focuses on actual experiences of patients who have type 1 diabetes; the second, Type 1: Attack of the Ketones, is aimed at professionals who may provide care but have limited understanding of type 1 diabetes; and the third, Type 1 Mission 3: S.T.I.G.M.A., addresses the stigmas and misconceptions that patients with type 1 diabetes may face.

The idea for the first comic was inspired by a patient who compared having diabetes to being like the Marvel character The Hulk, said Dr. Kar, and has been expanded to include the additional volumes.

Dr. Kar and Dr. Patel have also just launched the fourth comic in the series, Type 1: Generations, to mark the 100-year anniversary since insulin was first given to a human.
 

“This is high priority”  

Dr. Kar said the NHS in England has just appointed a national lead for type 1 diabetes in youth, Fulya Mehta, MD, of Alder Hey Children’s NHS Foundation Trust, Liverpool, England.

“If you have a plan, bring it to us,” he told the audience at the DPC conference, and “tell us, what is the one thing you would change? This is not a session we are doing just to tick a box. This is high priority.

“Encourage your colleagues to think about transition services. This is an absolute priority. We will be asking every center [in England] who is your transitioning lead?”

And he once again stressed that “a lead of transition service does not have to be a medic. This should be a multidisciplinary team. But they do need to be comfortable in that space. To that teenager, your job title means nothing. Give them time and space.”

Dr. Randell summed it up: “If we can work together, it’s only going to result in better outcomes. We need to blaze the trail for young people.”

Dr. Aleppo has reported serving as a consultant to Dexcom and Insulet and receiving support to Northwestern University from AstraZeneca, Dexcom, Eli Lilly, Fractyl Health, Insulet, and Novo Nordisk. Dr. Randell and Dr. Kar have no conflicts of interest.

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

More than a month after the launch of the new iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program, the operation still isn’t running smoothly for many dermatologists, pharmacists, and patients. That’s despite improvement attempts by the Food and Drug Administration, which mandates the program to prevent fetal exposure to the teratogenic effects of isotretinoin, and by the American Academy of Dermatology Association, whose members have repeatedly asked the FDA for meetings to discuss solutions. The AADA is the legislative and advocacy arm of AAD.

When the new program launched Dec. 13, 2021, the website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they tried to follow instructions to enter information. Hold times to talk to a live person stretched to hours.

The latest improvement attempt, announced Jan. 14 by the FDA, is a tool created by the Isotretinoin Products Manufacturers Group, the manufacturers responsible for the FDA-mandated REMS program. It is meant to allow prescribers and designees to send log-in links directly to patients’ email accounts through the iPLEDGE REMS portal, bypassing the troublesome call center.

And it’s not the answer, dermatologists said.

“The new tool does not solve issues such as prescribers or pharmacies not being able to access the site, unacceptably long call center wait times, inefficiencies caused by frequent attestation requirements for those who cannot become pregnant, patients becoming ‘locked out’ because they missed a window period through no fault of their own, among others,” said John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital and instructor in dermatology at Harvard Medical School, both in Boston.

The day after the FDA update about the new tool, Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., tweeted: “Lip service and empty words.” He noted that the situation has been “disastrous from the start” as the new platform launched.

Under the iPLEDGE program in place for the acne drug, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The aim of the new gender-neutral approach to the risk mitigation program is to make the experience more inclusive for transgender patients. The previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) are now reduced to just two (those capable of getting pregnant and those not capable of getting pregnant).

The problem is  the execution of the new platform. The transition from the old website to the new was done quickly. By most accounts, the Dec. 13 rollout was chaotic, a failure, and disastrous, triggering numerous expressions of frustration on Twitter and other social media, with some calling for the program to be halted until the bugs could be worked out.

“While the new gender-neutral categories are a welcome improvement to the system, the new categorization approach was not the underlying reason for the new platform and its failed rollout, which was instead due to a change in vendor,” Dr. Barbieri told this news organization.

AADA: More recent efforts to improve the system

“We have a letter to the FDA asking for a stakeholders meeting to include us, the IPMG, and pharmacists because there are ongoing problems, though there have been some improvement in terms of certain elements,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco, said in an interview shortly after the FDA posted the update on the new tool. “That said, there are many patients who have not gotten isotretinoin during the 1 month since the roll-out of the new platform.”

What still needs to be fixed? “We have ongoing concerns about the lack of transparency of the IPMG, about call center wait times, actual number of prescriptions on the hands of patients compared to the previous month, and those patients who can get pregnant who – despite complying with all of the REMS requirements – are being locked out because of the lack of timely attestation to their negative pregnancy status due to the website, not the patients themselves,” Dr. Frieden told this news organization.

“We are continuing to advocate to have decreased attestation requirements for individuals who cannot become pregnant – because this will improve the efficiency of the system for those patients for whom the REMS program goals are truly intended – those who can become pregnant, since the primary aim of the REMS program is to minimize fetal exposure.”

An AADA spokesperson said that the IPMG has invited the AADA to a joint stakeholders meeting on Jan. 26, along with representatives from the FDA and pharmacy industry.
 

Spotty progress

“The iPLEDGE situation is as frustrating as ever,” said Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, after the FDA’s Jan. 14 update was released. “It’s like they never tested the new website before deploying it.”

Among the issues he has experienced in his practice, he said, is an instance in which iPLEDGE swapped the first names of a mother and daughter, so it was impossible to fill the prescription. “It happened twice in the same day,” Dr. Goldberg said. The patient had to call iPLEDGE to fix this, but the call center wasn’t taking calls.

In today’s technology environment, he said, it’s hard to believe that “we have to put up with this.”

Some have seen success. ‘’The tool is working fine on our end,” said Mitesh Patel, PharmD, pharmacy manager at Sunshine Pharmacy in White Plains, N.Y. However, he added that some doctors and patients are still having issues. He encourages dermatologists still having issues with the system to reach out to independent pharmacies that have processed iPLEDGE prescriptions and ‘’lean on them to assist.”

This news organization contacted CVS and Walgreens about how the system is working at their locations, but has not yet received a response. 

Dr. Goldberg, Dr. Frieden, Dr. Barbieri, and Dr. Peebles have disclosed no relevant financial relationships.

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

This story was updated on 1/24/22.

More than a month after the launch of the new iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program, the operation still isn’t running smoothly for many dermatologists, pharmacists, and patients. That’s despite improvement attempts by the Food and Drug Administration, which mandates the program to prevent fetal exposure to the teratogenic effects of isotretinoin, and by the American Academy of Dermatology Association, whose members have repeatedly asked the FDA for meetings to discuss solutions. The AADA is the legislative and advocacy arm of AAD.

When the new program launched Dec. 13, 2021, the website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they tried to follow instructions to enter information. Hold times to talk to a live person stretched to hours.

The latest improvement attempt, announced Jan. 14 by the FDA, is a tool created by the Isotretinoin Products Manufacturers Group, the manufacturers responsible for the FDA-mandated REMS program. It is meant to allow prescribers and designees to send log-in links directly to patients’ email accounts through the iPLEDGE REMS portal, bypassing the troublesome call center.

And it’s not the answer, dermatologists said.

“The new tool does not solve issues such as prescribers or pharmacies not being able to access the site, unacceptably long call center wait times, inefficiencies caused by frequent attestation requirements for those who cannot become pregnant, patients becoming ‘locked out’ because they missed a window period through no fault of their own, among others,” said John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital and instructor in dermatology at Harvard Medical School, both in Boston.

The day after the FDA update about the new tool, Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., tweeted: “Lip service and empty words.” He noted that the situation has been “disastrous from the start” as the new platform launched.

Under the iPLEDGE program in place for the acne drug, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The aim of the new gender-neutral approach to the risk mitigation program is to make the experience more inclusive for transgender patients. The previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) are now reduced to just two (those capable of getting pregnant and those not capable of getting pregnant).

The problem is  the execution of the new platform. The transition from the old website to the new was done quickly. By most accounts, the Dec. 13 rollout was chaotic, a failure, and disastrous, triggering numerous expressions of frustration on Twitter and other social media, with some calling for the program to be halted until the bugs could be worked out.

“While the new gender-neutral categories are a welcome improvement to the system, the new categorization approach was not the underlying reason for the new platform and its failed rollout, which was instead due to a change in vendor,” Dr. Barbieri told this news organization.

AADA: More recent efforts to improve the system

“We have a letter to the FDA asking for a stakeholders meeting to include us, the IPMG, and pharmacists because there are ongoing problems, though there have been some improvement in terms of certain elements,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco, said in an interview shortly after the FDA posted the update on the new tool. “That said, there are many patients who have not gotten isotretinoin during the 1 month since the roll-out of the new platform.”

What still needs to be fixed? “We have ongoing concerns about the lack of transparency of the IPMG, about call center wait times, actual number of prescriptions on the hands of patients compared to the previous month, and those patients who can get pregnant who – despite complying with all of the REMS requirements – are being locked out because of the lack of timely attestation to their negative pregnancy status due to the website, not the patients themselves,” Dr. Frieden told this news organization.

“We are continuing to advocate to have decreased attestation requirements for individuals who cannot become pregnant – because this will improve the efficiency of the system for those patients for whom the REMS program goals are truly intended – those who can become pregnant, since the primary aim of the REMS program is to minimize fetal exposure.”

An AADA spokesperson said that the IPMG has invited the AADA to a joint stakeholders meeting on Jan. 26, along with representatives from the FDA and pharmacy industry.
 

Spotty progress

“The iPLEDGE situation is as frustrating as ever,” said Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, after the FDA’s Jan. 14 update was released. “It’s like they never tested the new website before deploying it.”

Among the issues he has experienced in his practice, he said, is an instance in which iPLEDGE swapped the first names of a mother and daughter, so it was impossible to fill the prescription. “It happened twice in the same day,” Dr. Goldberg said. The patient had to call iPLEDGE to fix this, but the call center wasn’t taking calls.

In today’s technology environment, he said, it’s hard to believe that “we have to put up with this.”

Some have seen success. ‘’The tool is working fine on our end,” said Mitesh Patel, PharmD, pharmacy manager at Sunshine Pharmacy in White Plains, N.Y. However, he added that some doctors and patients are still having issues. He encourages dermatologists still having issues with the system to reach out to independent pharmacies that have processed iPLEDGE prescriptions and ‘’lean on them to assist.”

This news organization contacted CVS and Walgreens about how the system is working at their locations, but has not yet received a response. 

Dr. Goldberg, Dr. Frieden, Dr. Barbieri, and Dr. Peebles have disclosed no relevant financial relationships.

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

This story was updated on 1/24/22.

More than a month after the launch of the new iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program, the operation still isn’t running smoothly for many dermatologists, pharmacists, and patients. That’s despite improvement attempts by the Food and Drug Administration, which mandates the program to prevent fetal exposure to the teratogenic effects of isotretinoin, and by the American Academy of Dermatology Association, whose members have repeatedly asked the FDA for meetings to discuss solutions. The AADA is the legislative and advocacy arm of AAD.

When the new program launched Dec. 13, 2021, the website crashed repeatedly, with physicians and patients complaining they got locked out or bounced off the platform when they tried to follow instructions to enter information. Hold times to talk to a live person stretched to hours.

The latest improvement attempt, announced Jan. 14 by the FDA, is a tool created by the Isotretinoin Products Manufacturers Group, the manufacturers responsible for the FDA-mandated REMS program. It is meant to allow prescribers and designees to send log-in links directly to patients’ email accounts through the iPLEDGE REMS portal, bypassing the troublesome call center.

And it’s not the answer, dermatologists said.

“The new tool does not solve issues such as prescribers or pharmacies not being able to access the site, unacceptably long call center wait times, inefficiencies caused by frequent attestation requirements for those who cannot become pregnant, patients becoming ‘locked out’ because they missed a window period through no fault of their own, among others,” said John Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital and instructor in dermatology at Harvard Medical School, both in Boston.

The day after the FDA update about the new tool, Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., tweeted: “Lip service and empty words.” He noted that the situation has been “disastrous from the start” as the new platform launched.

Under the iPLEDGE program in place for the acne drug, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The aim of the new gender-neutral approach to the risk mitigation program is to make the experience more inclusive for transgender patients. The previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) are now reduced to just two (those capable of getting pregnant and those not capable of getting pregnant).

The problem is  the execution of the new platform. The transition from the old website to the new was done quickly. By most accounts, the Dec. 13 rollout was chaotic, a failure, and disastrous, triggering numerous expressions of frustration on Twitter and other social media, with some calling for the program to be halted until the bugs could be worked out.

“While the new gender-neutral categories are a welcome improvement to the system, the new categorization approach was not the underlying reason for the new platform and its failed rollout, which was instead due to a change in vendor,” Dr. Barbieri told this news organization.

AADA: More recent efforts to improve the system

“We have a letter to the FDA asking for a stakeholders meeting to include us, the IPMG, and pharmacists because there are ongoing problems, though there have been some improvement in terms of certain elements,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE Workgroup and professor of dermatology at the University of California, San Francisco, said in an interview shortly after the FDA posted the update on the new tool. “That said, there are many patients who have not gotten isotretinoin during the 1 month since the roll-out of the new platform.”

What still needs to be fixed? “We have ongoing concerns about the lack of transparency of the IPMG, about call center wait times, actual number of prescriptions on the hands of patients compared to the previous month, and those patients who can get pregnant who – despite complying with all of the REMS requirements – are being locked out because of the lack of timely attestation to their negative pregnancy status due to the website, not the patients themselves,” Dr. Frieden told this news organization.

“We are continuing to advocate to have decreased attestation requirements for individuals who cannot become pregnant – because this will improve the efficiency of the system for those patients for whom the REMS program goals are truly intended – those who can become pregnant, since the primary aim of the REMS program is to minimize fetal exposure.”

An AADA spokesperson said that the IPMG has invited the AADA to a joint stakeholders meeting on Jan. 26, along with representatives from the FDA and pharmacy industry.
 

Spotty progress

“The iPLEDGE situation is as frustrating as ever,” said Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, after the FDA’s Jan. 14 update was released. “It’s like they never tested the new website before deploying it.”

Among the issues he has experienced in his practice, he said, is an instance in which iPLEDGE swapped the first names of a mother and daughter, so it was impossible to fill the prescription. “It happened twice in the same day,” Dr. Goldberg said. The patient had to call iPLEDGE to fix this, but the call center wasn’t taking calls.

In today’s technology environment, he said, it’s hard to believe that “we have to put up with this.”

Some have seen success. ‘’The tool is working fine on our end,” said Mitesh Patel, PharmD, pharmacy manager at Sunshine Pharmacy in White Plains, N.Y. However, he added that some doctors and patients are still having issues. He encourages dermatologists still having issues with the system to reach out to independent pharmacies that have processed iPLEDGE prescriptions and ‘’lean on them to assist.”

This news organization contacted CVS and Walgreens about how the system is working at their locations, but has not yet received a response. 

Dr. Goldberg, Dr. Frieden, Dr. Barbieri, and Dr. Peebles have disclosed no relevant financial relationships.

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

This story was updated on 1/24/22.

“Turns out smarter kids are made, not born.” The headline of the article leapt off the computer screen. Although I realize that it has limits when it comes to dissuading vaccine refusers, I believe that education is a critical element in the success of individuals and the societies they inhabit. However, I must admit to a bias based on my observations that, in general, cognitive skill is inherited. This is an opinion I suspect I share with most folks. You can understand why the article I discovered describing a recent study by several Harvard-based researchers caught my attention.

The study involved 33 mothers and their 1-year-old children. The researchers found that infants whose mothers were stressed and had a “fixed mindset” had lower brain activity than the infants of stressed mothers who held a “growth mindset.” You may be on top of the education literature but I had to do some heavy Googling to learn what was up with growth and fixed mindsets. Was this just a new riff on the whole mindfulness thing?

I quickly learned that in 2006 Carol Dweck, PhD, a psychologist now at Stanford, published a book titled “Mindset” (New York: Penguin Random House) in which she described individuals with a “fixed mindset” who believe that their personality or intelligence will not change over time. On the other hand, individuals with a “growth mindset” view their intelligence and personality as malleable. Her observations have spread across the education and self-help literature like a wildfire that has somehow been roaring along under my radar. I guess I have noticed a subtle change in emphasis when I hear some parents and educators praising a child’s effort in situations in which I might have expected them to say, “You’re so smart.” But, in general I have been clueless.

My initial impression was that this mindset stuff was just coining new buzz words to differentiate optimists from pessimists. But, here I am again revealing a fixed mindset bias. I probably should have said that someone demonstrating a growth mindset approach is “exercising optimism” instead of implying that they were simply born with a sunny disposition.

The growth mindset revolution has not been without skeptics and critics, which is not surprising because educators have a history of jumping on bandwagons before all the wheels have been completely tightened. However, the mindset approach does have some merit, especially for individuals in the center of the bell-shaped curve. We all know of individuals who have failed to meet or have exceeded what would seem to be rational expectations. It is likely that the degree to which a growth mindset approach was applied may be the explanation.

Which brings me to the question of whether we as pediatricians should be more careful of how we choose our words when talking to patients and parents. If the results of the study that alerted me to the growth mindset are reproducible, maybe we should be spending more time with new parents (all of whom are stressed by definition), helping them discover ways in which they can improve the situation they find themselves in by praising them for their efforts at parenting.

Should we be modeling growth mindset language by using it when we interact with our patients? For example, not just complimenting a child on the acquisition of a skill but adding that we were even more impressed by the effort required to acquire it. When we hear a parent clearly expressing a fixed mindset in describing their child should we correct them on the spot or make an appointment to discuss how adopting a growth mindset might help their child meet or exceed his or her potential?

Most smart children may be born that way, but there are always opportunities for improvement, and our patients and their parents need to believe that.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

“Turns out smarter kids are made, not born.” The headline of the article leapt off the computer screen. Although I realize that it has limits when it comes to dissuading vaccine refusers, I believe that education is a critical element in the success of individuals and the societies they inhabit. However, I must admit to a bias based on my observations that, in general, cognitive skill is inherited. This is an opinion I suspect I share with most folks. You can understand why the article I discovered describing a recent study by several Harvard-based researchers caught my attention.

The study involved 33 mothers and their 1-year-old children. The researchers found that infants whose mothers were stressed and had a “fixed mindset” had lower brain activity than the infants of stressed mothers who held a “growth mindset.” You may be on top of the education literature but I had to do some heavy Googling to learn what was up with growth and fixed mindsets. Was this just a new riff on the whole mindfulness thing?

I quickly learned that in 2006 Carol Dweck, PhD, a psychologist now at Stanford, published a book titled “Mindset” (New York: Penguin Random House) in which she described individuals with a “fixed mindset” who believe that their personality or intelligence will not change over time. On the other hand, individuals with a “growth mindset” view their intelligence and personality as malleable. Her observations have spread across the education and self-help literature like a wildfire that has somehow been roaring along under my radar. I guess I have noticed a subtle change in emphasis when I hear some parents and educators praising a child’s effort in situations in which I might have expected them to say, “You’re so smart.” But, in general I have been clueless.

My initial impression was that this mindset stuff was just coining new buzz words to differentiate optimists from pessimists. But, here I am again revealing a fixed mindset bias. I probably should have said that someone demonstrating a growth mindset approach is “exercising optimism” instead of implying that they were simply born with a sunny disposition.

The growth mindset revolution has not been without skeptics and critics, which is not surprising because educators have a history of jumping on bandwagons before all the wheels have been completely tightened. However, the mindset approach does have some merit, especially for individuals in the center of the bell-shaped curve. We all know of individuals who have failed to meet or have exceeded what would seem to be rational expectations. It is likely that the degree to which a growth mindset approach was applied may be the explanation.

Which brings me to the question of whether we as pediatricians should be more careful of how we choose our words when talking to patients and parents. If the results of the study that alerted me to the growth mindset are reproducible, maybe we should be spending more time with new parents (all of whom are stressed by definition), helping them discover ways in which they can improve the situation they find themselves in by praising them for their efforts at parenting.

Should we be modeling growth mindset language by using it when we interact with our patients? For example, not just complimenting a child on the acquisition of a skill but adding that we were even more impressed by the effort required to acquire it. When we hear a parent clearly expressing a fixed mindset in describing their child should we correct them on the spot or make an appointment to discuss how adopting a growth mindset might help their child meet or exceed his or her potential?

Most smart children may be born that way, but there are always opportunities for improvement, and our patients and their parents need to believe that.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

“Turns out smarter kids are made, not born.” The headline of the article leapt off the computer screen. Although I realize that it has limits when it comes to dissuading vaccine refusers, I believe that education is a critical element in the success of individuals and the societies they inhabit. However, I must admit to a bias based on my observations that, in general, cognitive skill is inherited. This is an opinion I suspect I share with most folks. You can understand why the article I discovered describing a recent study by several Harvard-based researchers caught my attention.

The study involved 33 mothers and their 1-year-old children. The researchers found that infants whose mothers were stressed and had a “fixed mindset” had lower brain activity than the infants of stressed mothers who held a “growth mindset.” You may be on top of the education literature but I had to do some heavy Googling to learn what was up with growth and fixed mindsets. Was this just a new riff on the whole mindfulness thing?

I quickly learned that in 2006 Carol Dweck, PhD, a psychologist now at Stanford, published a book titled “Mindset” (New York: Penguin Random House) in which she described individuals with a “fixed mindset” who believe that their personality or intelligence will not change over time. On the other hand, individuals with a “growth mindset” view their intelligence and personality as malleable. Her observations have spread across the education and self-help literature like a wildfire that has somehow been roaring along under my radar. I guess I have noticed a subtle change in emphasis when I hear some parents and educators praising a child’s effort in situations in which I might have expected them to say, “You’re so smart.” But, in general I have been clueless.

My initial impression was that this mindset stuff was just coining new buzz words to differentiate optimists from pessimists. But, here I am again revealing a fixed mindset bias. I probably should have said that someone demonstrating a growth mindset approach is “exercising optimism” instead of implying that they were simply born with a sunny disposition.

The growth mindset revolution has not been without skeptics and critics, which is not surprising because educators have a history of jumping on bandwagons before all the wheels have been completely tightened. However, the mindset approach does have some merit, especially for individuals in the center of the bell-shaped curve. We all know of individuals who have failed to meet or have exceeded what would seem to be rational expectations. It is likely that the degree to which a growth mindset approach was applied may be the explanation.

Which brings me to the question of whether we as pediatricians should be more careful of how we choose our words when talking to patients and parents. If the results of the study that alerted me to the growth mindset are reproducible, maybe we should be spending more time with new parents (all of whom are stressed by definition), helping them discover ways in which they can improve the situation they find themselves in by praising them for their efforts at parenting.

Should we be modeling growth mindset language by using it when we interact with our patients? For example, not just complimenting a child on the acquisition of a skill but adding that we were even more impressed by the effort required to acquire it. When we hear a parent clearly expressing a fixed mindset in describing their child should we correct them on the spot or make an appointment to discuss how adopting a growth mindset might help their child meet or exceed his or her potential?

Most smart children may be born that way, but there are always opportunities for improvement, and our patients and their parents need to believe that.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Two close colleagues at New York’s Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic’s impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”

Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Courtesy MSKCC

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”

When it comes to clinical science, however, English is the language of choice.
 

Global leaders in HSCT

Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

Courtesy MSKCC

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.

Impact of the pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
 

Something more in common

Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.

He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”

“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”

Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”

This article was updated 1/26/22.

Two close colleagues at New York’s Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic’s impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”

Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Courtesy MSKCC

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”

When it comes to clinical science, however, English is the language of choice.
 

Global leaders in HSCT

Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

Courtesy MSKCC

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.

Impact of the pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
 

Something more in common

Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.

He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”

“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”

Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”

This article was updated 1/26/22.

Two close colleagues at New York’s Memorial Sloan Kettering Cancer Center, world leaders in hematopoietic stem cell transplantation (HSCT) who were both promoted days after COVID-19 locked down the city in 2020, were too busy battling the pandemic’s impact on patients in the summer of 2021 to notice their latest shared career milestone.

On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.

Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.

Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.

Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”

Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.

Courtesy MSKCC

Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.

“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”

When it comes to clinical science, however, English is the language of choice.
 

Global leaders in HSCT

Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.

In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).

However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.

Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).

Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.

The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.

Courtesy MSKCC

The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.

During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).

The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.

The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.

Impact of the pandemic

When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”

The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.

“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
 

Something more in common

Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.

“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.

He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.

Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”

“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”

Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”

This article was updated 1/26/22.

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

THE CASE

Paul F* is a 16-year-old White boy who lives with his mother and spends some weekends with his father who has shared custody. He recently presented to the clinic for treatment due to an arrest for disorderly conduct at school. He and a friend were found drinking liquor outside the school building when they were scheduled to be in class. Paul reported that he and his friends often drink at school and at extracurricular functions. He has been using alcohol for the past 2 years, with escalating consumption (5 or more drinks per episode) in the past year. Paul has been drinking most days of the week and has even driven under the influence at times. He said, “I just feel happier when I am drinking.” An accomplished soccer player recruited by colleges, Paul recently was suspended from the team due to his poor grades. His response was, “It’s stupid anyway. What’s the point of playing?”

● How would you proceed with this patient?

* The patient’s name and some personal details have been changed to protect his identity.

Alcohol is the number 1 substance of abuse for adolescents, used more than tobacco or drugs.^1-3 In 2007 and again in 2016, the Surgeon General of the United States issued reports to highlight this important topic,^1,2 noting that early and repeated exposure to alcohol during this crucial time of brain development increases the risk for future problems, including addiction.²

Adolescent alcohol use is often underestimated by parents and physicians, including misjudging how much, how often, and how young children are when they begin to drink.¹ Boys and girls tend to start drinking at similar ages (13.9 and 14.4 years, respectively),³ but as girls age, they tend to drink more and binge more.⁴ In 2019, 1 in 4 adolescents reported drinking and more than 4 million reported at least 1 episode of binge drinking in the prior month.⁴ These numbers have further ramifications: early drinking is associated with alcohol dependence, relapse, use of other substances, risky sexual behaviors, injurious behaviors, suicide, motor vehicle accidents, and dating violence.^4-6

Diagnosing alcohol use disorder

The range of alcohol use includes consumption, bingeing, abuse, and dependence.^7,8 Consumption is defined as the drinking of alcoholic beverages. Bingeing is the consumption of more than 5 drinks for men or 4 drinks for women in 2 hours, according to the National Institute on Alcohol Abuse and Alcoholism.⁷ However, the criterion is slightly different for the Substance Abuse and Mental Health Services Administration, which broadens the timeframe to “on the same occasion.”⁹ While previously known as separate disorders, alcohol abuse (or misuse) and alcohol dependence are now diagnostically classified together as alcohol use disorders (AUDs), per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).⁸ AUD is further stratified as mild, moderate, or severe, depending on the number of criteria that are met by the patient (TABLE).^8,10

Alcohol screening

Currently, the US Preventive Services Task Force (USPSTF) does not recommend screening adolescents ages 12 to 17 for AUD, and has instead issued an “I” statement (insufficient evidence).¹¹ While the USPSTF recognizes the potential burdens of adolescent alcohol use, the potential harms of screening include “stigma, anxiety, labeling, discrimination, privacy concerns, and interference with the patient–clinician relationship.”¹¹ The USPSTF also notes that it “did not find any evidence that specifically examined the harms of screening for alcohol use in adolescents.”¹¹

The Screening to Brief Intervention (S2BI) tool can quickly and efficiently stratify a patient’s risk of substance use disorder.

This is at odds with recommendations from the American Academy of Pediatrics (AAP), which in 2011 released a policy statement advocating screening, brief intervention, and referral to treatment for adolescent substance use.¹² In the United States, even though 83% of adolescents see a physician at least once each year,^12,13 alcohol misuse screening still varies, occurring in the range of 50% to 86% of office visits.¹² When screening does occur, it is often based on clinical impression only.¹² Studies have shown that when a screening tool is not used, up to two-thirds of substance use disorders may be missed.^12-15

Continue to: A full and complete biopsychosocial interview

A full and complete biopsychosocial interview with adolescents is a necessity, and should include queries about alcohol, drugs, and other substances. Acknowledgment of use should trigger further investigation into the substance use areas. Interviews may start with open-ended questions about alcohol use at home or at school before moving to more personalized and detailed questioning and use of screening tools.¹⁶

While various screening instruments exist, for the sake of brevity we provide as an example the Screening to Brief Intervention (S2BI) tool. It is an efficient, single-page tool that can help clinicians in their routine care of adolescents to quickly stratify the patient risk of substance use disorder as none/low, moderate, or severe.¹² It can be found here: www.mcpap.com/pdf/S2Bi%20Toolkit.pdf (see page 10).

Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and alcohol use disorder.

For all patients, but particularly for adolescents, confidentiality is important, and many specialty societies have created language to address this issue.¹² Discuss confidentiality with both the adolescent patient and the patient’s caregiver simultaneously, with dialogue that includes: (a) the need to speak with adolescents alone during the office visit, (b) the benefits of confidentiality in the ­physician–patient relationship, and (c) the need to disclose selected information to keep patients safe.¹² Describing the process for required disclosures is essential. Benefits of disclosure include further support for the adolescent patient as well as appropriate parental participation and support for possible referrals.¹²

Treating AUD  

Treatment for AUD should be multifaceted. Screen for comorbid mood disorders, such as generalized anxiety,^17,18 social anxiety,¹⁸ and depression,¹⁹ as well as for insomnia.¹⁸ Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and AUD.^17-19 Finally, screen for adverse childhood events such as trauma, victimization, and abuse.²⁰ Addressing issues discovered in screening allows for more targeted and personalized treatment of AUD.

The National Institute on Drug Abuse categorizes evidence-based treatment into 3 areas: behavioral therapies, family therapies, and medications.²¹

Continue to: Behavioral therapies

Behavioral therapies can include group therapy, cognitive behavioral therapy (CBT), motivational enhancement therapy, 12-Step facilitation, and contingency management, in which small rewards or incentives are given for participation in treatment to reinforce positive behaviors.²¹

Family-based therapies, such as brief strategic family therapy, functional family therapy, and multisystem therapy recognize that adolescents exist in systems of families in communities, and that the patient’s success in treatment may be supported by these relationships.²¹

Some medications may achieve modest benefit for treatment of adolescents with AUD. Naltrexone, acamprosate, and disulfiram have all been used successfully to treat AUD in adults²¹; some physicians may choose to use these medications “off label” in adolescents. Bupropion has been used successfully in the treatment of nicotine use disorder,²¹ and a small study in 2005 showed some success with bupropion in treating adolescents with ­attention-deficit/hyperactivity disorder, comorbid depression, and substance use disorder.²² Naltrexone has also been studied in adolescents with opioid use disorder, although these were not large studies.²³

Adolescents with serious, sustained issues with AUD may require more in-depth treatments such as an intensive outpatient program, a partial hospitalization program, or a residential treatment program.¹⁵ The least-­restrictive environment is preferable.¹⁵ Families are generally included as part of the treatment and recovery process in those settings.²¹ Some patients may require detoxification prior to referral to residential treatment settings; the American Society of Addiction Medicine has published a comprehensive guideline on alcohol withdrawal.²⁴

THE CASE

Paul’s family physician diagnosed his condition as AUD and referred him for CBT with a psychologist, who treated him for both the AUD and an underlying depressive disorder that was later identified. CBT focused on cognitive restructuring of depressive thoughts as well as support for continued abstinence from alcohol. The patient, with family support, declined antidepressant medication.

After 6 months of treatment, Paul and his parents were pleased with his progress. His grades improved to the point that he was permitted to play soccer again, and he was seriously looking at his future college options.

CORRESPONDENCE
Scott A. Fields, PhD, 3200 MacCorkle Avenue Southeast, 5th Floor, Robert C. Byrd Clinical Teaching Center, Department of Family Medicine, Charleston, WV 25304; sfields@hsc.wvu.edu

THE CASE

Paul F* is a 16-year-old White boy who lives with his mother and spends some weekends with his father who has shared custody. He recently presented to the clinic for treatment due to an arrest for disorderly conduct at school. He and a friend were found drinking liquor outside the school building when they were scheduled to be in class. Paul reported that he and his friends often drink at school and at extracurricular functions. He has been using alcohol for the past 2 years, with escalating consumption (5 or more drinks per episode) in the past year. Paul has been drinking most days of the week and has even driven under the influence at times. He said, “I just feel happier when I am drinking.” An accomplished soccer player recruited by colleges, Paul recently was suspended from the team due to his poor grades. His response was, “It’s stupid anyway. What’s the point of playing?”

● How would you proceed with this patient?

* The patient’s name and some personal details have been changed to protect his identity.

Alcohol is the number 1 substance of abuse for adolescents, used more than tobacco or drugs.^1-3 In 2007 and again in 2016, the Surgeon General of the United States issued reports to highlight this important topic,^1,2 noting that early and repeated exposure to alcohol during this crucial time of brain development increases the risk for future problems, including addiction.²

Adolescent alcohol use is often underestimated by parents and physicians, including misjudging how much, how often, and how young children are when they begin to drink.¹ Boys and girls tend to start drinking at similar ages (13.9 and 14.4 years, respectively),³ but as girls age, they tend to drink more and binge more.⁴ In 2019, 1 in 4 adolescents reported drinking and more than 4 million reported at least 1 episode of binge drinking in the prior month.⁴ These numbers have further ramifications: early drinking is associated with alcohol dependence, relapse, use of other substances, risky sexual behaviors, injurious behaviors, suicide, motor vehicle accidents, and dating violence.^4-6

Diagnosing alcohol use disorder

The range of alcohol use includes consumption, bingeing, abuse, and dependence.^7,8 Consumption is defined as the drinking of alcoholic beverages. Bingeing is the consumption of more than 5 drinks for men or 4 drinks for women in 2 hours, according to the National Institute on Alcohol Abuse and Alcoholism.⁷ However, the criterion is slightly different for the Substance Abuse and Mental Health Services Administration, which broadens the timeframe to “on the same occasion.”⁹ While previously known as separate disorders, alcohol abuse (or misuse) and alcohol dependence are now diagnostically classified together as alcohol use disorders (AUDs), per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).⁸ AUD is further stratified as mild, moderate, or severe, depending on the number of criteria that are met by the patient (TABLE).^8,10

Alcohol screening

Currently, the US Preventive Services Task Force (USPSTF) does not recommend screening adolescents ages 12 to 17 for AUD, and has instead issued an “I” statement (insufficient evidence).¹¹ While the USPSTF recognizes the potential burdens of adolescent alcohol use, the potential harms of screening include “stigma, anxiety, labeling, discrimination, privacy concerns, and interference with the patient–clinician relationship.”¹¹ The USPSTF also notes that it “did not find any evidence that specifically examined the harms of screening for alcohol use in adolescents.”¹¹

The Screening to Brief Intervention (S2BI) tool can quickly and efficiently stratify a patient’s risk of substance use disorder.

This is at odds with recommendations from the American Academy of Pediatrics (AAP), which in 2011 released a policy statement advocating screening, brief intervention, and referral to treatment for adolescent substance use.¹² In the United States, even though 83% of adolescents see a physician at least once each year,^12,13 alcohol misuse screening still varies, occurring in the range of 50% to 86% of office visits.¹² When screening does occur, it is often based on clinical impression only.¹² Studies have shown that when a screening tool is not used, up to two-thirds of substance use disorders may be missed.^12-15

Continue to: A full and complete biopsychosocial interview

A full and complete biopsychosocial interview with adolescents is a necessity, and should include queries about alcohol, drugs, and other substances. Acknowledgment of use should trigger further investigation into the substance use areas. Interviews may start with open-ended questions about alcohol use at home or at school before moving to more personalized and detailed questioning and use of screening tools.¹⁶

While various screening instruments exist, for the sake of brevity we provide as an example the Screening to Brief Intervention (S2BI) tool. It is an efficient, single-page tool that can help clinicians in their routine care of adolescents to quickly stratify the patient risk of substance use disorder as none/low, moderate, or severe.¹² It can be found here: www.mcpap.com/pdf/S2Bi%20Toolkit.pdf (see page 10).

Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and alcohol use disorder.

For all patients, but particularly for adolescents, confidentiality is important, and many specialty societies have created language to address this issue.¹² Discuss confidentiality with both the adolescent patient and the patient’s caregiver simultaneously, with dialogue that includes: (a) the need to speak with adolescents alone during the office visit, (b) the benefits of confidentiality in the ­physician–patient relationship, and (c) the need to disclose selected information to keep patients safe.¹² Describing the process for required disclosures is essential. Benefits of disclosure include further support for the adolescent patient as well as appropriate parental participation and support for possible referrals.¹²

Treating AUD  

Treatment for AUD should be multifaceted. Screen for comorbid mood disorders, such as generalized anxiety,^17,18 social anxiety,¹⁸ and depression,¹⁹ as well as for insomnia.¹⁸ Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and AUD.^17-19 Finally, screen for adverse childhood events such as trauma, victimization, and abuse.²⁰ Addressing issues discovered in screening allows for more targeted and personalized treatment of AUD.

The National Institute on Drug Abuse categorizes evidence-based treatment into 3 areas: behavioral therapies, family therapies, and medications.²¹

Continue to: Behavioral therapies

Behavioral therapies can include group therapy, cognitive behavioral therapy (CBT), motivational enhancement therapy, 12-Step facilitation, and contingency management, in which small rewards or incentives are given for participation in treatment to reinforce positive behaviors.²¹

Family-based therapies, such as brief strategic family therapy, functional family therapy, and multisystem therapy recognize that adolescents exist in systems of families in communities, and that the patient’s success in treatment may be supported by these relationships.²¹

Some medications may achieve modest benefit for treatment of adolescents with AUD. Naltrexone, acamprosate, and disulfiram have all been used successfully to treat AUD in adults²¹; some physicians may choose to use these medications “off label” in adolescents. Bupropion has been used successfully in the treatment of nicotine use disorder,²¹ and a small study in 2005 showed some success with bupropion in treating adolescents with ­attention-deficit/hyperactivity disorder, comorbid depression, and substance use disorder.²² Naltrexone has also been studied in adolescents with opioid use disorder, although these were not large studies.²³

Adolescents with serious, sustained issues with AUD may require more in-depth treatments such as an intensive outpatient program, a partial hospitalization program, or a residential treatment program.¹⁵ The least-­restrictive environment is preferable.¹⁵ Families are generally included as part of the treatment and recovery process in those settings.²¹ Some patients may require detoxification prior to referral to residential treatment settings; the American Society of Addiction Medicine has published a comprehensive guideline on alcohol withdrawal.²⁴

THE CASE

Paul’s family physician diagnosed his condition as AUD and referred him for CBT with a psychologist, who treated him for both the AUD and an underlying depressive disorder that was later identified. CBT focused on cognitive restructuring of depressive thoughts as well as support for continued abstinence from alcohol. The patient, with family support, declined antidepressant medication.

After 6 months of treatment, Paul and his parents were pleased with his progress. His grades improved to the point that he was permitted to play soccer again, and he was seriously looking at his future college options.

CORRESPONDENCE
Scott A. Fields, PhD, 3200 MacCorkle Avenue Southeast, 5th Floor, Robert C. Byrd Clinical Teaching Center, Department of Family Medicine, Charleston, WV 25304; sfields@hsc.wvu.edu

THE CASE

Paul F* is a 16-year-old White boy who lives with his mother and spends some weekends with his father who has shared custody. He recently presented to the clinic for treatment due to an arrest for disorderly conduct at school. He and a friend were found drinking liquor outside the school building when they were scheduled to be in class. Paul reported that he and his friends often drink at school and at extracurricular functions. He has been using alcohol for the past 2 years, with escalating consumption (5 or more drinks per episode) in the past year. Paul has been drinking most days of the week and has even driven under the influence at times. He said, “I just feel happier when I am drinking.” An accomplished soccer player recruited by colleges, Paul recently was suspended from the team due to his poor grades. His response was, “It’s stupid anyway. What’s the point of playing?”

● How would you proceed with this patient?

* The patient’s name and some personal details have been changed to protect his identity.

Alcohol is the number 1 substance of abuse for adolescents, used more than tobacco or drugs.^1-3 In 2007 and again in 2016, the Surgeon General of the United States issued reports to highlight this important topic,^1,2 noting that early and repeated exposure to alcohol during this crucial time of brain development increases the risk for future problems, including addiction.²

Adolescent alcohol use is often underestimated by parents and physicians, including misjudging how much, how often, and how young children are when they begin to drink.¹ Boys and girls tend to start drinking at similar ages (13.9 and 14.4 years, respectively),³ but as girls age, they tend to drink more and binge more.⁴ In 2019, 1 in 4 adolescents reported drinking and more than 4 million reported at least 1 episode of binge drinking in the prior month.⁴ These numbers have further ramifications: early drinking is associated with alcohol dependence, relapse, use of other substances, risky sexual behaviors, injurious behaviors, suicide, motor vehicle accidents, and dating violence.^4-6

Diagnosing alcohol use disorder

The range of alcohol use includes consumption, bingeing, abuse, and dependence.^7,8 Consumption is defined as the drinking of alcoholic beverages. Bingeing is the consumption of more than 5 drinks for men or 4 drinks for women in 2 hours, according to the National Institute on Alcohol Abuse and Alcoholism.⁷ However, the criterion is slightly different for the Substance Abuse and Mental Health Services Administration, which broadens the timeframe to “on the same occasion.”⁹ While previously known as separate disorders, alcohol abuse (or misuse) and alcohol dependence are now diagnostically classified together as alcohol use disorders (AUDs), per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).⁸ AUD is further stratified as mild, moderate, or severe, depending on the number of criteria that are met by the patient (TABLE).^8,10

Alcohol screening

Currently, the US Preventive Services Task Force (USPSTF) does not recommend screening adolescents ages 12 to 17 for AUD, and has instead issued an “I” statement (insufficient evidence).¹¹ While the USPSTF recognizes the potential burdens of adolescent alcohol use, the potential harms of screening include “stigma, anxiety, labeling, discrimination, privacy concerns, and interference with the patient–clinician relationship.”¹¹ The USPSTF also notes that it “did not find any evidence that specifically examined the harms of screening for alcohol use in adolescents.”¹¹

The Screening to Brief Intervention (S2BI) tool can quickly and efficiently stratify a patient’s risk of substance use disorder.

This is at odds with recommendations from the American Academy of Pediatrics (AAP), which in 2011 released a policy statement advocating screening, brief intervention, and referral to treatment for adolescent substance use.¹² In the United States, even though 83% of adolescents see a physician at least once each year,^12,13 alcohol misuse screening still varies, occurring in the range of 50% to 86% of office visits.¹² When screening does occur, it is often based on clinical impression only.¹² Studies have shown that when a screening tool is not used, up to two-thirds of substance use disorders may be missed.^12-15

Continue to: A full and complete biopsychosocial interview

A full and complete biopsychosocial interview with adolescents is a necessity, and should include queries about alcohol, drugs, and other substances. Acknowledgment of use should trigger further investigation into the substance use areas. Interviews may start with open-ended questions about alcohol use at home or at school before moving to more personalized and detailed questioning and use of screening tools.¹⁶

While various screening instruments exist, for the sake of brevity we provide as an example the Screening to Brief Intervention (S2BI) tool. It is an efficient, single-page tool that can help clinicians in their routine care of adolescents to quickly stratify the patient risk of substance use disorder as none/low, moderate, or severe.¹² It can be found here: www.mcpap.com/pdf/S2Bi%20Toolkit.pdf (see page 10).

Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and alcohol use disorder.

For all patients, but particularly for adolescents, confidentiality is important, and many specialty societies have created language to address this issue.¹² Discuss confidentiality with both the adolescent patient and the patient’s caregiver simultaneously, with dialogue that includes: (a) the need to speak with adolescents alone during the office visit, (b) the benefits of confidentiality in the ­physician–patient relationship, and (c) the need to disclose selected information to keep patients safe.¹² Describing the process for required disclosures is essential. Benefits of disclosure include further support for the adolescent patient as well as appropriate parental participation and support for possible referrals.¹²

Treating AUD  

Treatment for AUD should be multifaceted. Screen for comorbid mood disorders, such as generalized anxiety,^17,18 social anxiety,¹⁸ and depression,¹⁹ as well as for insomnia.¹⁸ Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and AUD.^17-19 Finally, screen for adverse childhood events such as trauma, victimization, and abuse.²⁰ Addressing issues discovered in screening allows for more targeted and personalized treatment of AUD.

The National Institute on Drug Abuse categorizes evidence-based treatment into 3 areas: behavioral therapies, family therapies, and medications.²¹

Continue to: Behavioral therapies

Behavioral therapies can include group therapy, cognitive behavioral therapy (CBT), motivational enhancement therapy, 12-Step facilitation, and contingency management, in which small rewards or incentives are given for participation in treatment to reinforce positive behaviors.²¹

Family-based therapies, such as brief strategic family therapy, functional family therapy, and multisystem therapy recognize that adolescents exist in systems of families in communities, and that the patient’s success in treatment may be supported by these relationships.²¹

Some medications may achieve modest benefit for treatment of adolescents with AUD. Naltrexone, acamprosate, and disulfiram have all been used successfully to treat AUD in adults²¹; some physicians may choose to use these medications “off label” in adolescents. Bupropion has been used successfully in the treatment of nicotine use disorder,²¹ and a small study in 2005 showed some success with bupropion in treating adolescents with ­attention-deficit/hyperactivity disorder, comorbid depression, and substance use disorder.²² Naltrexone has also been studied in adolescents with opioid use disorder, although these were not large studies.²³

Adolescents with serious, sustained issues with AUD may require more in-depth treatments such as an intensive outpatient program, a partial hospitalization program, or a residential treatment program.¹⁵ The least-­restrictive environment is preferable.¹⁵ Families are generally included as part of the treatment and recovery process in those settings.²¹ Some patients may require detoxification prior to referral to residential treatment settings; the American Society of Addiction Medicine has published a comprehensive guideline on alcohol withdrawal.²⁴

THE CASE

Paul’s family physician diagnosed his condition as AUD and referred him for CBT with a psychologist, who treated him for both the AUD and an underlying depressive disorder that was later identified. CBT focused on cognitive restructuring of depressive thoughts as well as support for continued abstinence from alcohol. The patient, with family support, declined antidepressant medication.

After 6 months of treatment, Paul and his parents were pleased with his progress. His grades improved to the point that he was permitted to play soccer again, and he was seriously looking at his future college options.

CORRESPONDENCE
Scott A. Fields, PhD, 3200 MacCorkle Avenue Southeast, 5th Floor, Robert C. Byrd Clinical Teaching Center, Department of Family Medicine, Charleston, WV 25304; sfields@hsc.wvu.edu

When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.

“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.

Courtesy DKMS.org

In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.

“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.

Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).

In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”

From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.

Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
 

World’s largest registry

“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.

“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,

In 2022, DKMS is the largest global bone marrow donor recruitment organization, with more than 10.6 million potential donors registered. Worldwide, more than 91,000 patients have received bone marrow or stem cell grafts donated by registered volunteers.

Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.

Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
 

Global partners

DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.

“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.

The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
 

Pandemic affects donations

But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.

Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.

“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.

However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.

“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
 

Workforce and clinical problems

Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.

“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.

“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.

Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.

“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.

In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.

“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.

To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.

The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
 

‘Every patient saved’

The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.

DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.

In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.

The last word goes to Mechtild Harf’s daughter Katharina.

“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”

“I have to believe that this dream will come true because otherwise, why dream, right?” she said.

Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.

When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.

“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.

Courtesy DKMS.org

In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.

“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.

Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).

In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”

From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.

Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
 

World’s largest registry

“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.

“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,

In 2022, DKMS is the largest global bone marrow donor recruitment organization, with more than 10.6 million potential donors registered. Worldwide, more than 91,000 patients have received bone marrow or stem cell grafts donated by registered volunteers.

Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.

Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
 

Global partners

DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.

“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.

The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
 

Pandemic affects donations

But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.

Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.

“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.

However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.

“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
 

Workforce and clinical problems

Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.

“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.

“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.

Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.

“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.

In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.

“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.

To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.

The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
 

‘Every patient saved’

The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.

DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.

In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.

The last word goes to Mechtild Harf’s daughter Katharina.

“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”

“I have to believe that this dream will come true because otherwise, why dream, right?” she said.

Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.

When Mechtild Harf was diagnosed with acute leukemia in 1990, physicians told her and her husband Peter that a bone marrow transplant was her best hope for survival. Back then, her native Germany had only 3,000 registered donors, and none was a match.

“My dad just went crazy, you know, to save his wife,” recalled Katharina Harf, who was a young teen at the time of her mother’s diagnosis.

Courtesy DKMS.org

In the course of 1 year, the Harfs recruited more than 68,000 potential bone marrow donors, but their heroic efforts couldn’t save Mechtild.

“She unfortunately didn’t make it. She died because of leukemia,” Katharina said.

Although Mechtild Harf did not survive, her legacy lives on in the bone marrow and stem cell donor recruitment organization DKMS (Deutsche Knochenmarkspenderdatei, or German Bone Marrow Donor Center).

In May of 1991, Peter Harf and Gerhard Ehninger, MD, the hematologist who treated Mechtild, founded DKMS with the mission, as its website states, “to provide as many blood cancer patients as possible with a second chance at life.”

From its German roots, the nonprofit organization has extended its mission to the United States (where it was initially known as Delete Blood Cancer DKMS), Poland, the United Kingdom, Chile, and in 2021, to South Africa.

Three decades after her mother’s death, Katharina Harf serves as Executive Chairwoman of DKMS U.S., based in New York.
 

World’s largest registry

“DKMS has the largest number of unrelated donors of any organization in the world,” noted Richard E. Champlin, MD, chair of the department of stem cell transplantation and cellular therapy at the University of Texas MD Anderson Cancer Center in Houston.

“In a large fraction of our donor searches, we find matches that are in the DKMS registry,” he said in an interview,

In 2022, DKMS is the largest global bone marrow donor recruitment organization, with more than 10.6 million potential donors registered. Worldwide, more than 91,000 patients have received bone marrow or stem cell grafts donated by registered volunteers.

Alexander Schmidt, MD, PhD, global chief medical officer for DKMS, said that approximately 25% of all registered donors worldwide were recruited by his organization, and 39% of all unrelated donor transplants are made with peripheral blood stem cell or bone marrow products, donated by volunteers who are recruited by DKMS.

Since its founding, DKMS has registered 7.1 million potential donors in Germany, who made a total of 80,000 stem cell donations. DKMS U.S., which began operations in 2004, has registered 1.1 million donors and enabled 4,700 donations.
 

Global partners

DKMS partners with donor centers and recruitment organizations in each country where it operates. In the United States, DKMS works with the National Marrow Donor Program (NMDP) and its “Be The Match” donor registry.

“DKMS donors, both those from DKMS in Germany and those from DKMS in the United States are also listed in the NMDP registry, to make it easier for US search coordinators to accept these donors,” Dr. Schmidt explained in an interview.

The international cooperation and coordination makes it possible for a donor in the UK, for example, to save a life of a patient in Germany, the U.S., Chile, India, or many other parts of the world – anywhere that can be reached in time for a patient in need to receive a stem cell donation.
 

Pandemic affects donations

But, as with just about every aspect of life, the COVID-19 pandemic has created enormous challenges for recruiters, donor centers, and stem cell transplant centers.

Dr. Schmidt said that decline in donations during the pandemic was less severe than initially feared, with a decrease of just 3.5% in 2020, compared with the prepandemic year of 2019. In contrast, though, the average annual growth rate for donations prior to the pandemic was about 4%.

“Nevertheless, at the beginning of the pandemic in March 2020, for a few days things looked quite terrible, because all the borders were closed and flights were canceled, and about 50% of all stem cell products go abroad, and between 20% and 25% go intercontinental,” Dr. Schmidt said.

However, close cooperation and coordination between donor centers and national health authorities soon resolved the problem and helped insure that the flow of life-saving donations could continue with minimal disruption, he noted.

“I don’t think we had any product that could not be delivered at the end of the day, due to the pandemic,” he told this news organization.
 

Workforce and clinical problems

Although the flow of donations within and between nations has continued, the COVID-19 pandemic has had profound negative effects on transplant centers, particularly during the wave of infections caused by the Omicron variant, according to a transplant expert.

“With this most recent strain and how transmissible it is, what we’re dealing with is mass workforce shortages,” said Yi-Bin Chen, MD, director of the bone marrow transplant program at Massachusetts General Hospital in Boston.

“On top of a short-staffed hospital, you then take a very transmissible variant and deplete it even more due to the need to quarantine,” he said in an interview.

Both Dr. Champlin and Dr. Chen said that on-again, off-again pandemic travel bans and donor illnesses have necessitated first obtaining products and cryopreserving them before starting the recipient on a conditioning regimen for the transplant.

“The problem is that, while you can preserve peripheral blood stem cells pretty reliably, cryopreserving bone marrow is a bit more difficult,” Dr. Chen said.

In addition, evidence from recent studies comparing stem cell sources suggest that outcomes are less good with cryopreserved products than with fresh products, and with peripheral blood stem cells compared with bone marrow.

“But you’ve got to make do. A transplant with a cryopreserved product is better than no transplant,” Dr. Chen said.

To make things even more frustrating, as the pandemic waxed and waned throughout 2020 and 2021, the recommendations from donor centers seesawed between using fresh or cryopreserved product, making it difficult to plan a transplant for an individual patient.

The Omicron wave has also resulted in a much higher rate of donor dropout than anticipated, making it that much harder to schedule a transplant, Dr. Chen noted.
 

‘Every patient saved’

The pandemic will eventually subside, however, while the need for stem cell transplantation to treat hematologic malignancies will continue.

DKMS recently launched special aid programs to improve access to stem cell transplants in developing nations by offering financial support, free HLA typing, and other services.

In addition to its core mission of recruiting donors, DKMS is dedicated to improving the quality and efficiency of stem cell transplants. For example, in 2017 scientists in DKMS’ Life Science Lab created an antibody test for donor cytomegalovirus (CMV) infection, using a simple buccal swab rather than a more invasive blood sample. CMV infections can compromise the integrity of stem cell grafts and could be fatal to immunocompromised transplant recipients.

The last word goes to Mechtild Harf’s daughter Katharina.

“My big dream is that every patient will be saved from blood cancer,” she said in a video posted on the DKMS website. “When they get sick, we have a solution for them, whether it’s because they need a donor, with research, building hospitals, providing them with the best medical care we can. I will just keep fighting and keep spreading the word, recruiting donors, raising money – all the things that it takes for us to delete blood cancer.”

“I have to believe that this dream will come true because otherwise, why dream, right?” she said.

Dr. Champlin was the recipient of a Mechtild Harf Science Award and is a member of the board of DKMS U.S. Dr. Schmidt is employed by DKMS. Dr. Chen reported having no relevant disclosures.

A semiautomated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1-7 years without increasing hypoglycemia.

“Hybrid closed-loop” systems – comprising an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semiautomates insulin delivery based on glucose levels – have been shown to improve glucose control in older children and adults.

Gilnature/iStock/Getty Images

The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, said the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge (England). The findings were published online Jan. 19, 2022, in the New England Journal of Medicine.

“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.

There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Dr. Ware and colleagues noted.

“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to ... reduced quality of life for the whole family,” they added.
 

Except for mealtimes, device is fully automated

The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the United Kingdom in 2019-2020.

The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline hemoglobin A1c of 7.3% (56.6 mmol/mol).

The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.

The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.

Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explained in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.

“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”

Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).

That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three-quarters of their day (71.6%) in the target range, the investigators wrote.  

The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).

At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop, compared with the control period (P < .001).

That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Dr. Ware and colleagues noted.

Median glucose sensor use was 99% during the closed-loop period and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.

This finding supports longer-term usability in this age group and compares well with use in older children, they said.

One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.

“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Dr. Ware summarized.
 

Sleep quality could improve for children and caregivers

Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculated.

In addition, they noted that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality of life benefits.”

“Parents have described our artificial pancreas as ‘life changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Dr. Ware.

The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Dr. Hovorka. It is currently available through several NHS trusts across the United Kingdom, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.

The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Dr. Ware had no further disclosures. Dr. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.

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

A semiautomated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1-7 years without increasing hypoglycemia.

“Hybrid closed-loop” systems – comprising an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semiautomates insulin delivery based on glucose levels – have been shown to improve glucose control in older children and adults.

Gilnature/iStock/Getty Images

The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, said the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge (England). The findings were published online Jan. 19, 2022, in the New England Journal of Medicine.

“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.

There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Dr. Ware and colleagues noted.

“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to ... reduced quality of life for the whole family,” they added.
 

Except for mealtimes, device is fully automated

The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the United Kingdom in 2019-2020.

The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline hemoglobin A1c of 7.3% (56.6 mmol/mol).

The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.

The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.

Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explained in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.

“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”

Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).

That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three-quarters of their day (71.6%) in the target range, the investigators wrote.  

The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).

At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop, compared with the control period (P < .001).

That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Dr. Ware and colleagues noted.

Median glucose sensor use was 99% during the closed-loop period and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.

This finding supports longer-term usability in this age group and compares well with use in older children, they said.

One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.

“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Dr. Ware summarized.
 

Sleep quality could improve for children and caregivers

Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculated.

In addition, they noted that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality of life benefits.”

“Parents have described our artificial pancreas as ‘life changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Dr. Ware.

The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Dr. Hovorka. It is currently available through several NHS trusts across the United Kingdom, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.

The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Dr. Ware had no further disclosures. Dr. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.

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

A semiautomated insulin delivery system improved glycemic control in young children with type 1 diabetes aged 1-7 years without increasing hypoglycemia.

“Hybrid closed-loop” systems – comprising an insulin pump, a continuous glucose monitor (CGM), and software enabling communication that semiautomates insulin delivery based on glucose levels – have been shown to improve glucose control in older children and adults.

Gilnature/iStock/Getty Images

The technology, also known as an artificial pancreas, has been less studied in very young children even though it may uniquely benefit them, said the authors of the new study, led by Julia Ware, MD, of the Wellcome Trust–Medical Research Council Institute of Metabolic Science and the University of Cambridge (England). The findings were published online Jan. 19, 2022, in the New England Journal of Medicine.

“Very young children are extremely vulnerable to changes in their blood sugar levels. High levels in particular can have potentially lasting consequences to their brain development. On top of that, diabetes is very challenging to manage in this age group, creating a huge burden for families,” she said in a University of Cambridge statement.

There is “high variability of insulin requirements, marked insulin sensitivity, and unpredictable eating and activity patterns,” Dr. Ware and colleagues noted.

“Caregiver fear of hypoglycemia, particularly overnight, is common and, coupled with young children’s unawareness that hypoglycemia is occurring, contributes to children not meeting the recommended glycemic targets or having difficulty maintaining recommended glycemic control unless caregivers can provide constant monitoring. These issues often lead to ... reduced quality of life for the whole family,” they added.
 

Except for mealtimes, device is fully automated

The new multicenter, randomized, crossover trial was conducted at seven centers across Austria, Germany, Luxembourg, and the United Kingdom in 2019-2020.

The trial compared the safety and efficacy of hybrid closed-loop therapy with sensor-augmented pump therapy (that is, without the device communication, as a control). All 74 children used the CamAPS FX hybrid closed-loop system for 16 weeks, and then used the control treatment for 16 weeks. The children were a mean age of 5.6 years and had a baseline hemoglobin A1c of 7.3% (56.6 mmol/mol).

The hybrid closed-loop system consisted of components that are commercially available in Europe: the Sooil insulin pump (Dana Diabecare RS) and the Dexcom G6 CGM, along with an unlocked Samsung Galaxy 8 smartphone housing an app (CamAPS FX, CamDiab) that runs the Cambridge proprietary model predictive control algorithm.

The smartphone communicates wirelessly with both the pump and the CGM transmitter and automatically adjusts the pump’s insulin delivery based on real-time sensor glucose readings. It also issues alarms if glucose levels fall below or rise above user-specified thresholds. This functionality was disabled during the study control periods.

Senior investigator Roman Hovorka, PhD, who developed the CamAPS FX app, explained in the University of Cambridge statement that the app “makes predictions about what it thinks is likely to happen next based on past experience. It learns how much insulin the child needs per day and how this changes at different times of the day.

“It then uses this [information] to adjust insulin levels to help achieve ideal blood sugar levels. Other than at mealtimes, it is fully automated, so parents do not need to continually monitor their child’s blood sugar levels.”

Indeed, the time spent in target glucose range (70-180 mg/dL) during the 16-week closed-loop period was 8.7 percentage points higher than during the control period (P < .001).

That difference translates to “a clinically meaningful 125 minutes per day,” and represented around three-quarters of their day (71.6%) in the target range, the investigators wrote.  

The mean adjusted difference in time spent above 180 mg/dL was 8.5 percentage points lower with the closed-loop, also a significant difference (P < .001). Time spent below 70 mg/dL did not differ significantly between the two interventions (P = .74).

At the end of the study periods, the mean adjusted between-treatment difference in A1c was –0.4 percentage points, significantly lower following the closed-loop, compared with the control period (P < .001).

That percentage point difference (equivalent to 3.9 mmol/mol) “is important in a population of patients who had tight glycemic control at baseline. This result was observed without an increase in the time spent in a hypoglycemic state,” Dr. Ware and colleagues noted.

Median glucose sensor use was 99% during the closed-loop period and 96% during the control periods. During the closed-loop periods, the system was in closed-loop mode 95% of the time.

This finding supports longer-term usability in this age group and compares well with use in older children, they said.

One serious hypoglycemic episode, attributed to parental error rather than system malfunction, occurred during the closed-loop period. There were no episodes of diabetic ketoacidosis. Rates of other adverse events didn’t differ between the two periods.

“CamAPS FX led to improvements in several measures, including hyperglycemia and average blood sugar levels, without increasing the risk of hypos. This is likely to have important benefits for those children who use it,” Dr. Ware summarized.
 

Sleep quality could improve for children and caregivers

Reductions in time spent in hyperglycemia without increasing hypoglycemia could minimize the risk for neurocognitive deficits that have been reported among young children with type 1 diabetes, the authors speculated.

In addition, they noted that because 80% of overnight sensor readings were within target range and less than 3% were below 70 mg/dL, sleep quality could improve for both the children and their parents. This, in turn, “would confer associated quality of life benefits.”

“Parents have described our artificial pancreas as ‘life changing’ as it meant they were able to relax and spend less time worrying about their child’s blood sugar levels, particularly at nighttime. They tell us it gives them more time to do what any ‘normal’ family can do, to play and do fun things with their children,” observed Dr. Ware.

The CamAPS FX has been commercialized by CamDiab, a spin-out company set up by Dr. Hovorka. It is currently available through several NHS trusts across the United Kingdom, including Cambridge University Hospitals NHS Foundation Trust, and is expected to be more widely available soon.

The study was supported by the European Commission within the Horizon 2020 Framework Program, the NIHR Cambridge Biomedical Research Centre, and JDRF. Dr. Ware had no further disclosures. Dr. Hovorka has reported acting as consultant for Abbott Diabetes Care, BD, Dexcom, being a speaker for Novo Nordisk and Eli Lilly, and receiving royalty payments from B. Braun for software. He is director of CamDiab.

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

Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.

A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.

The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.

Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.

The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.

The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.

The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.

“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”

Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.

The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.

The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.

Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.

“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.

The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.

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

Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.

A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.

The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.

Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.

The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.

The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.

The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.

“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”

Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.

The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.

The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.

Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.

“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.

The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.

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

Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.

A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.

The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.

Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.

The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.

The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.

The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.

“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”

Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.

The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.

The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.

Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.

“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.

The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.

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