Hormone therapy for menopausal symptoms has come a long way in the past decade, but some low risks remain, particularly for certain groups of women. But new naturally occurring estrogens are on the horizon and may provide safer options with similar efficacy for treating hot flashes and other symptoms, researchers report.

“Unfortunately, there is no such thing as the perfect estrogen that has all the things that makes it favorable and none of the negative,” Hugh S. Taylor, MD, told attendees at the virtual annual meeting of the North American Menopause Society. “It probably doesn’t exist. But there’s an opportunity for us to design better estrogens or take advantage of other naturally occurring estrogens that come closer to that goal of the ideal estrogen,” said Dr. Taylor, professor and chair of ob.gyn. and reproductive sciences at Yale University, New Haven, Conn.

Those naturally occurring estrogens are the fetal estrogens, estetrol and estriol, which are produced almost exclusively during pregnancy. Only estetrol has been investigated in clinical trials, and it does show some promise, Dr. Taylor said.

“If there’s a better cardiovascular effect without the breast cancer risk, this could be something everyone would want to take,” Dr. Taylor said in an interview. “It’s the first new estrogen we’ve had in many years, and it makes so much sense that we go back to a naturally occurring estrogen. We’ve never really been able to get a synthetic estrogen [that works].”
 

Hormone therapy still most effective for vasomotor symptoms

The primary benefits of hormone therapy for postmenopausal women are decreased hot flashes and night sweats and the prevention of bone loss, vaginal dryness, and vaginal atrophy. But as women age, particularly past age 70 years, the risks for stroke, heart disease, and breast cancer associated with hormone therapy begin to outweigh the benefits.

That leaves women who are still experiencing those symptoms in a quandary.

“Some people will take on substantial risks because they want to continue taking hormones,” Nanette F. Santoro, MD, a professor of ob.gyn. at the University of Colorado at Denver, Aurora, said in an interview. “If they understand what they’re doing and they tell me that they are that miserable, then I will continue their hormones.”

Dr. Santoro, who was not involved in Taylor’s work, said some patients have seen her because their primary care providers refused to continue prescribing them hormones at their age, despite serious vasomotor symptoms that interfered with their daily life.

“Women are sometimes not taken seriously, and I think that’s a problem,” Dr. Santoro said. “Women need to be able to make an informed choice about what kinds of risk they’re taking on. Many physicians’ rationales are that hot flashes never killed anybody. Well, they can sure make you miserable.”

Dr. Taylor echoed the importance of taking women’s symptoms seriously and helping them choose the most effective treatments to manage their symptoms.

“The rush of adrenaline, the anxiety, the palpitations, the heart racing, the sweating, all the night sweats [that mean] you can’t sleep at night, and the lack of adequate REM sleep – all these things add up and can really be disruptive to someone’s life,” Dr. Taylor said in an interview. “I think it’s important that we raise awareness of how severe it can be, about just how low the risks [of hormone therapy] are, and get people more comfortable using hormone therapy, but also continue to search for safer, better products that will eliminate even those low risks.”

A major development toward that goal in the past decade has been therapies that combine an estrogen with a selective estrogen receptor modulator (SERM), which have antiestrogen effects in the endometrium and breast without blocking estrogen in the bones and brain.

One such tissue-selective estrogen complex (TSEC) is the combination of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg). Clinical trials showed that this TSEC reduced the frequency of hot flashes by 74%, compared with 47% with placebo. In addition, TSEC reduced the severity of hot flashes by 39%, compared with 13% with placebo. The combination also improved bone density at the spine and hip without promoting endometrial hyperplasia.

“It looks like it does exactly what we want,” Dr. Taylor told NAMS attendees. “The SERM is antagonizing the effects of the estrogens in the endometrium but not in the bone or brain.” It also led to a decrease in total cholesterol, and there was no increase in breast stimulation or density.

Another advance in recent years has been more choices and more precision with dosing, Dr. Santoro said.

“Where inroads have been made is in having women be aware of all the options they have and in getting the most convenient compounds to people,” she said, despite the confusion and misinformation that have arisen from the proliferation of bioidenticals. “You can dial in a dose for just about anybody.”
 

New estrogens in the pipeline

Neither of these developments, however, have eliminated the risks associated with hormone therapy for women of older age or for women at high risk for breast cancer. Although total elimination of risk may not be possible, recent research suggests that the naturally occurring fetal estrogens estriol and estetrol appear to have SERM-like properties, Dr. Taylor said. These estrogens are made only in pregnancy and appear to have evolved for a purpose different from that of estrone and estradiol.

“While both are weak estrogens by traditional standards, both have unique properties that make them very interesting for therapeutic use,” Dr. Taylor said. In particular, estetrol has a much longer half-life than estriol, making it more appropriate for therapeutic investigation.

A study of estetrol that was published in Menopause in August 2020 showed encouraging results. Despite a fairly sizable placebo effect, there was also a dose-response effect from estetrol on vasomotor symptoms. Low doses did not have much effect, but with higher doses (15 mg), there was a robust, significant improvement in the frequency and severity of hot flashes. So far, Dr. Taylor said, it looks like estetrol can be a highly effective treatment for vasomotor symptoms.

In addition, preclinical research suggests that estetrol may have a better safety profile than currently available therapies, though much more work is needed to know for sure. For example, a 2015 study found that it requires extremely high doses – well above therapeutic levels – for tumor growth to occur. Similarly, a 2019 study found that very high doses of estetrol or estriol were needed before it would stimulate breast cancer cell growth, likely because these are such weak estrogens, compared with estradiol, Dr. Taylor said.

There is currently less information on estetrol’s potential cardiovascular effects, but an animal model suggests positive effects, he said. Giving a mouse estetrol led to an increase in blood vessel dilation with increased blood flow.

The reason these estrogens appear to pose less risk yet still show therapeutic effects appears related to how they bind to the estrogen receptor and what their purpose is, Dr. Taylor told attendees.

“These fetal estrogens are really there probably for developmental programming,” he said. “It’s no wonder they may have some unique and favorable properties for therapeutic use. I’m really enthusiastic to see this explored further as a potential new hormonal therapy.”

Dr. Taylor disclosed no relevant financial relationships. Dr. Santoro reported stock ownership in Menogenix and consulting or advising for Ansh Labs, Menogenix, and Ogeda/Astellas.

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

Hormone therapy for menopausal symptoms has come a long way in the past decade, but some low risks remain, particularly for certain groups of women. But new naturally occurring estrogens are on the horizon and may provide safer options with similar efficacy for treating hot flashes and other symptoms, researchers report.

“Unfortunately, there is no such thing as the perfect estrogen that has all the things that makes it favorable and none of the negative,” Hugh S. Taylor, MD, told attendees at the virtual annual meeting of the North American Menopause Society. “It probably doesn’t exist. But there’s an opportunity for us to design better estrogens or take advantage of other naturally occurring estrogens that come closer to that goal of the ideal estrogen,” said Dr. Taylor, professor and chair of ob.gyn. and reproductive sciences at Yale University, New Haven, Conn.

Those naturally occurring estrogens are the fetal estrogens, estetrol and estriol, which are produced almost exclusively during pregnancy. Only estetrol has been investigated in clinical trials, and it does show some promise, Dr. Taylor said.

“If there’s a better cardiovascular effect without the breast cancer risk, this could be something everyone would want to take,” Dr. Taylor said in an interview. “It’s the first new estrogen we’ve had in many years, and it makes so much sense that we go back to a naturally occurring estrogen. We’ve never really been able to get a synthetic estrogen [that works].”
 

Hormone therapy still most effective for vasomotor symptoms

The primary benefits of hormone therapy for postmenopausal women are decreased hot flashes and night sweats and the prevention of bone loss, vaginal dryness, and vaginal atrophy. But as women age, particularly past age 70 years, the risks for stroke, heart disease, and breast cancer associated with hormone therapy begin to outweigh the benefits.

That leaves women who are still experiencing those symptoms in a quandary.

“Some people will take on substantial risks because they want to continue taking hormones,” Nanette F. Santoro, MD, a professor of ob.gyn. at the University of Colorado at Denver, Aurora, said in an interview. “If they understand what they’re doing and they tell me that they are that miserable, then I will continue their hormones.”

Dr. Santoro, who was not involved in Taylor’s work, said some patients have seen her because their primary care providers refused to continue prescribing them hormones at their age, despite serious vasomotor symptoms that interfered with their daily life.

“Women are sometimes not taken seriously, and I think that’s a problem,” Dr. Santoro said. “Women need to be able to make an informed choice about what kinds of risk they’re taking on. Many physicians’ rationales are that hot flashes never killed anybody. Well, they can sure make you miserable.”

Dr. Taylor echoed the importance of taking women’s symptoms seriously and helping them choose the most effective treatments to manage their symptoms.

“The rush of adrenaline, the anxiety, the palpitations, the heart racing, the sweating, all the night sweats [that mean] you can’t sleep at night, and the lack of adequate REM sleep – all these things add up and can really be disruptive to someone’s life,” Dr. Taylor said in an interview. “I think it’s important that we raise awareness of how severe it can be, about just how low the risks [of hormone therapy] are, and get people more comfortable using hormone therapy, but also continue to search for safer, better products that will eliminate even those low risks.”

A major development toward that goal in the past decade has been therapies that combine an estrogen with a selective estrogen receptor modulator (SERM), which have antiestrogen effects in the endometrium and breast without blocking estrogen in the bones and brain.

One such tissue-selective estrogen complex (TSEC) is the combination of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg). Clinical trials showed that this TSEC reduced the frequency of hot flashes by 74%, compared with 47% with placebo. In addition, TSEC reduced the severity of hot flashes by 39%, compared with 13% with placebo. The combination also improved bone density at the spine and hip without promoting endometrial hyperplasia.

“It looks like it does exactly what we want,” Dr. Taylor told NAMS attendees. “The SERM is antagonizing the effects of the estrogens in the endometrium but not in the bone or brain.” It also led to a decrease in total cholesterol, and there was no increase in breast stimulation or density.

Another advance in recent years has been more choices and more precision with dosing, Dr. Santoro said.

“Where inroads have been made is in having women be aware of all the options they have and in getting the most convenient compounds to people,” she said, despite the confusion and misinformation that have arisen from the proliferation of bioidenticals. “You can dial in a dose for just about anybody.”
 

New estrogens in the pipeline

Neither of these developments, however, have eliminated the risks associated with hormone therapy for women of older age or for women at high risk for breast cancer. Although total elimination of risk may not be possible, recent research suggests that the naturally occurring fetal estrogens estriol and estetrol appear to have SERM-like properties, Dr. Taylor said. These estrogens are made only in pregnancy and appear to have evolved for a purpose different from that of estrone and estradiol.

“While both are weak estrogens by traditional standards, both have unique properties that make them very interesting for therapeutic use,” Dr. Taylor said. In particular, estetrol has a much longer half-life than estriol, making it more appropriate for therapeutic investigation.

A study of estetrol that was published in Menopause in August 2020 showed encouraging results. Despite a fairly sizable placebo effect, there was also a dose-response effect from estetrol on vasomotor symptoms. Low doses did not have much effect, but with higher doses (15 mg), there was a robust, significant improvement in the frequency and severity of hot flashes. So far, Dr. Taylor said, it looks like estetrol can be a highly effective treatment for vasomotor symptoms.

In addition, preclinical research suggests that estetrol may have a better safety profile than currently available therapies, though much more work is needed to know for sure. For example, a 2015 study found that it requires extremely high doses – well above therapeutic levels – for tumor growth to occur. Similarly, a 2019 study found that very high doses of estetrol or estriol were needed before it would stimulate breast cancer cell growth, likely because these are such weak estrogens, compared with estradiol, Dr. Taylor said.

There is currently less information on estetrol’s potential cardiovascular effects, but an animal model suggests positive effects, he said. Giving a mouse estetrol led to an increase in blood vessel dilation with increased blood flow.

The reason these estrogens appear to pose less risk yet still show therapeutic effects appears related to how they bind to the estrogen receptor and what their purpose is, Dr. Taylor told attendees.

“These fetal estrogens are really there probably for developmental programming,” he said. “It’s no wonder they may have some unique and favorable properties for therapeutic use. I’m really enthusiastic to see this explored further as a potential new hormonal therapy.”

Dr. Taylor disclosed no relevant financial relationships. Dr. Santoro reported stock ownership in Menogenix and consulting or advising for Ansh Labs, Menogenix, and Ogeda/Astellas.

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

Hormone therapy for menopausal symptoms has come a long way in the past decade, but some low risks remain, particularly for certain groups of women. But new naturally occurring estrogens are on the horizon and may provide safer options with similar efficacy for treating hot flashes and other symptoms, researchers report.

“Unfortunately, there is no such thing as the perfect estrogen that has all the things that makes it favorable and none of the negative,” Hugh S. Taylor, MD, told attendees at the virtual annual meeting of the North American Menopause Society. “It probably doesn’t exist. But there’s an opportunity for us to design better estrogens or take advantage of other naturally occurring estrogens that come closer to that goal of the ideal estrogen,” said Dr. Taylor, professor and chair of ob.gyn. and reproductive sciences at Yale University, New Haven, Conn.

Those naturally occurring estrogens are the fetal estrogens, estetrol and estriol, which are produced almost exclusively during pregnancy. Only estetrol has been investigated in clinical trials, and it does show some promise, Dr. Taylor said.

“If there’s a better cardiovascular effect without the breast cancer risk, this could be something everyone would want to take,” Dr. Taylor said in an interview. “It’s the first new estrogen we’ve had in many years, and it makes so much sense that we go back to a naturally occurring estrogen. We’ve never really been able to get a synthetic estrogen [that works].”
 

Hormone therapy still most effective for vasomotor symptoms

The primary benefits of hormone therapy for postmenopausal women are decreased hot flashes and night sweats and the prevention of bone loss, vaginal dryness, and vaginal atrophy. But as women age, particularly past age 70 years, the risks for stroke, heart disease, and breast cancer associated with hormone therapy begin to outweigh the benefits.

That leaves women who are still experiencing those symptoms in a quandary.

“Some people will take on substantial risks because they want to continue taking hormones,” Nanette F. Santoro, MD, a professor of ob.gyn. at the University of Colorado at Denver, Aurora, said in an interview. “If they understand what they’re doing and they tell me that they are that miserable, then I will continue their hormones.”

Dr. Santoro, who was not involved in Taylor’s work, said some patients have seen her because their primary care providers refused to continue prescribing them hormones at their age, despite serious vasomotor symptoms that interfered with their daily life.

“Women are sometimes not taken seriously, and I think that’s a problem,” Dr. Santoro said. “Women need to be able to make an informed choice about what kinds of risk they’re taking on. Many physicians’ rationales are that hot flashes never killed anybody. Well, they can sure make you miserable.”

Dr. Taylor echoed the importance of taking women’s symptoms seriously and helping them choose the most effective treatments to manage their symptoms.

“The rush of adrenaline, the anxiety, the palpitations, the heart racing, the sweating, all the night sweats [that mean] you can’t sleep at night, and the lack of adequate REM sleep – all these things add up and can really be disruptive to someone’s life,” Dr. Taylor said in an interview. “I think it’s important that we raise awareness of how severe it can be, about just how low the risks [of hormone therapy] are, and get people more comfortable using hormone therapy, but also continue to search for safer, better products that will eliminate even those low risks.”

A major development toward that goal in the past decade has been therapies that combine an estrogen with a selective estrogen receptor modulator (SERM), which have antiestrogen effects in the endometrium and breast without blocking estrogen in the bones and brain.

One such tissue-selective estrogen complex (TSEC) is the combination of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg). Clinical trials showed that this TSEC reduced the frequency of hot flashes by 74%, compared with 47% with placebo. In addition, TSEC reduced the severity of hot flashes by 39%, compared with 13% with placebo. The combination also improved bone density at the spine and hip without promoting endometrial hyperplasia.

“It looks like it does exactly what we want,” Dr. Taylor told NAMS attendees. “The SERM is antagonizing the effects of the estrogens in the endometrium but not in the bone or brain.” It also led to a decrease in total cholesterol, and there was no increase in breast stimulation or density.

Another advance in recent years has been more choices and more precision with dosing, Dr. Santoro said.

“Where inroads have been made is in having women be aware of all the options they have and in getting the most convenient compounds to people,” she said, despite the confusion and misinformation that have arisen from the proliferation of bioidenticals. “You can dial in a dose for just about anybody.”
 

New estrogens in the pipeline

Neither of these developments, however, have eliminated the risks associated with hormone therapy for women of older age or for women at high risk for breast cancer. Although total elimination of risk may not be possible, recent research suggests that the naturally occurring fetal estrogens estriol and estetrol appear to have SERM-like properties, Dr. Taylor said. These estrogens are made only in pregnancy and appear to have evolved for a purpose different from that of estrone and estradiol.

“While both are weak estrogens by traditional standards, both have unique properties that make them very interesting for therapeutic use,” Dr. Taylor said. In particular, estetrol has a much longer half-life than estriol, making it more appropriate for therapeutic investigation.

A study of estetrol that was published in Menopause in August 2020 showed encouraging results. Despite a fairly sizable placebo effect, there was also a dose-response effect from estetrol on vasomotor symptoms. Low doses did not have much effect, but with higher doses (15 mg), there was a robust, significant improvement in the frequency and severity of hot flashes. So far, Dr. Taylor said, it looks like estetrol can be a highly effective treatment for vasomotor symptoms.

In addition, preclinical research suggests that estetrol may have a better safety profile than currently available therapies, though much more work is needed to know for sure. For example, a 2015 study found that it requires extremely high doses – well above therapeutic levels – for tumor growth to occur. Similarly, a 2019 study found that very high doses of estetrol or estriol were needed before it would stimulate breast cancer cell growth, likely because these are such weak estrogens, compared with estradiol, Dr. Taylor said.

There is currently less information on estetrol’s potential cardiovascular effects, but an animal model suggests positive effects, he said. Giving a mouse estetrol led to an increase in blood vessel dilation with increased blood flow.

The reason these estrogens appear to pose less risk yet still show therapeutic effects appears related to how they bind to the estrogen receptor and what their purpose is, Dr. Taylor told attendees.

“These fetal estrogens are really there probably for developmental programming,” he said. “It’s no wonder they may have some unique and favorable properties for therapeutic use. I’m really enthusiastic to see this explored further as a potential new hormonal therapy.”

Dr. Taylor disclosed no relevant financial relationships. Dr. Santoro reported stock ownership in Menogenix and consulting or advising for Ansh Labs, Menogenix, and Ogeda/Astellas.

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

Integrating ADHD care into practice work flows is vitally important for all practitioners who care for children, said Herschel Lessin, MD, a senior partner of the Children’s Medical Group in Poughkeepsie, N.Y.

O_Lypa/iStock/Getty Images

Although not necessarily “easy” to do, it’s far less overwhelming than it seems when doctors take the time to thoughtfully set up protocols, train others in the office, and use the ADHD Toolkit sold by the American Academy of Pediatrics, Dr. Lessin told attendees at the annual meeting of the AAP, held virtually this year. Dr. Lessin is a coeditor of the AAP’s ADHD Toolkit 3rd Ed., although he does not receive royalties from it. The toolkit includes patient handouts, clinicians tools, and rating scales that help practices incorporate ADHD care into their practices.

“The biggest complaint is: ‘But I don’t have enough time to do all of this stuff,’ ” Dr. Lessin said. “The reality is, once you’re comfortable with the visits and you know how they progress and flow, they can be done much more quickly.” He emphasized that practices can make money by integrating ADHD care into practice as long as they have a strategic plan and invest the time into training and protocols.

Dr. Lessin gave multiple reasons it’s important to integrate ADHD care into practices, starting with the condition’s prevalence and the importance of building a medical home for patients.

“ADHD affects 8%-10% of your patient population, a truly enormous number, yet many pediatricians do not treat ADHD in their practices, depriving their patients of needed care and depriving themselves from economic benefits of the visits and the revenue,” he said. The pediatrician added that more than 80% of ADHD care takes place in pediatric offices, but much of it is “badly diagnosed and poorly treated” in both primary care and specialty offices.

Jesse Hackell, MD, a private practice pediatrician in a suburb of New York City and vice president of the New York AAP Chapter 3, attended the session and agreed with Dr. Lessin that pediatricians are best suited to manage ADHD over other practitioners.

“One of the things he pointed out is that it’s a pediatric issue,” Dr. Hackell said. “We’re better at this than psychiatrists, than neurologists, than psychologists because we’re really focused on the whole lifestyle of the child, how it impacts them at home, how it impacts them at school, and how it impacts them in the social sphere.”

There’s also been a substantial increase in mental health issues as a proportion of visits, particularly recently with the pandemic and accompanying lockdowns. Youth already have limited access to mental health resources, making general pediatricians’ roles even more important. “Who else is going to provide this much needed service if not pediatricians?” Dr. Lessin asked.

Again, Dr. Hackell agreed, noting that the AAP’s toolkit is especially helpful in providing this care.

“It’s something that pediatricians have often been afraid to deal with and who farm them out to these other specialties, and I don’t think the children are served as well,” Dr. Hackell said. “If you do the right forms and questionnaires, you can actually make it work for the kids and work it for your office, which generates a lot of visits and generates revenue.”
 

Where to start

Dr. Lessin began by recommending that all pediatricians read the AAP’s clinical practice guidelines for ADHD along with its supplemental material (Process of Care Algorithm, and Systemic Barriers to Care of Children and Adolescents with ADHD).

“The first thing is you must educate yourself,” he said. “You have to learn the medicine and what are you able and comfortable doing because few of us were ever trained in our residency programs about ADHD care.”

Providers also need to learn to manage barriers to care, including referral sources and insurance company and medication hassles. Then you need to figure out how to structure the visits, determine the most appropriate visit settings, and learn to document and code appropriately. These are not quick 10-minute visits, Dr. Lessin said. Doctors must schedule enough time for them, although they may be able to do them faster with practice.

Dr. Lessin offered encouraging words for those feeling overwhelmed: “Overcome your anxiety. This is not as hard as it seems. It’s a little bit harder with comorbidities, but many chronic diseases we manage are far worse.”

In addition to reading the guidelines and review articles, seeking out mental health training programs, and learning the medications available, Dr. Lessin told attendees to get comfortable with the fact that a lot of treatment comes down to trial and error.

Again, he emphasized the value of the toolkit, which Dr. Hackell echoed.

“It’s a really nice roadmap to be able to follow and to explain how it requires two or three or four visits to treat these children well and get them started on treatment,” Dr. Hackell said. “It’s something that I recommend people use if they have not already done so to integrate ADHD care into their practices.”
 

Beginning the process

In figuring out how to structure visits, avoid addressing ADHD as a “by-the-way” issue, such as when a parent mentions it at the end of an appointment, Dr. Lessin said. Instead, start with an intake visit to determine whether you’re the right person to evaluate the child and hand out Parent and Teacher Evaluation scales to begin the process. Next, do the evaluation, discuss the process with the family, determine how treatment will work, and then look at comorbidities.

Visit settings can be traditional face-to-face visits, which are particularly helpful for intake visits, Dr. Lessin said, or telehealth, especially during the pandemic. In-person visits allow you more easily to make eye contact with the child and observe the parent and child behaviors and interactions, but telehealth often is adequate for titrating medication, discussing side effects, monitoring, and similar follow-up.

“Coding practices are absolutely necessary to make your practice viable, much less make money,” Dr. Lessin said. “Doing good for people and doing well for yourself are not mutually exclusive. You have to figure out a way to make it work economically for the practice or else you’re just not going to do it.”

He reminded pediatricians to code for evaluation, monitoring scales, and care coordination, and to be prepared for the big change of new coding rules coming in 2021.

“For better or worse, documentation is the key to survival in medical practice these days,” Dr. Lessin said. “This is true for all medical care these days, but it’s particularly true for ADHD because visits are all high intensity codes and should be coded as such.”

Templates are fine, he said, but box-checking isn’t enough; leave space for a narrative that explains the case complexity and decision-making.
 

Training staff is essential

It’s utterly essential to train all office staff, Dr. Lessin said. “I can’t tell you how important this step is because no matter how much you know or how well you understand what you want to do, you’re going to be frustrated at every turn if your staff and colleagues don’t get this stuff.”

That includes training those who make appointments, front desk staff, clinical staff, and practice colleagues regarding coding, scheduling, visit protocols, and similar procedures. Cheat sheets can be helpful here.

“They must understand the structure of the visits, what happens at each visit, the time requirements for each visit, and the standard follow-up,” including, for clinical staff, what handouts and rating scales to use, he said. “And if they aren’t sure what the parents needs or what you want, make sure they know to contact you.”

Colleagues also need to learn to properly document visits to justify coding and complexity, and not dump all patients on you.

One challenge that Dr. Lessin acknowledged as a common problem is that many pediatricians don’t have subspecialists they can refer patients to.

“Sadly, this is true almost everywhere, in rural and in big cities, near big medical centers and only local hospitals,” Dr. Lessin said. “This another reason why I think you need to learn and treat this illness to the extent you can. Your families need you.”

Dr. Hackell particularly appreciated this point, emphasizing again how important it is that pediatricians manage ADHD care of their patients.

“We see their day-to-day life, and that’s where this impacts these kids and families,” he said. “It’s really rewarding to do from my personal experience because you can really make a really big difference in these kids’ lives when they’re younger and even as they get older. When you get the rewards, it makes the work all worthwhile.”

Dr. Lessin and Dr. Hackell said they have no relevant financial disclosures.

Integrating ADHD care into practice work flows is vitally important for all practitioners who care for children, said Herschel Lessin, MD, a senior partner of the Children’s Medical Group in Poughkeepsie, N.Y.

O_Lypa/iStock/Getty Images

Although not necessarily “easy” to do, it’s far less overwhelming than it seems when doctors take the time to thoughtfully set up protocols, train others in the office, and use the ADHD Toolkit sold by the American Academy of Pediatrics, Dr. Lessin told attendees at the annual meeting of the AAP, held virtually this year. Dr. Lessin is a coeditor of the AAP’s ADHD Toolkit 3rd Ed., although he does not receive royalties from it. The toolkit includes patient handouts, clinicians tools, and rating scales that help practices incorporate ADHD care into their practices.

“The biggest complaint is: ‘But I don’t have enough time to do all of this stuff,’ ” Dr. Lessin said. “The reality is, once you’re comfortable with the visits and you know how they progress and flow, they can be done much more quickly.” He emphasized that practices can make money by integrating ADHD care into practice as long as they have a strategic plan and invest the time into training and protocols.

Dr. Lessin gave multiple reasons it’s important to integrate ADHD care into practices, starting with the condition’s prevalence and the importance of building a medical home for patients.

“ADHD affects 8%-10% of your patient population, a truly enormous number, yet many pediatricians do not treat ADHD in their practices, depriving their patients of needed care and depriving themselves from economic benefits of the visits and the revenue,” he said. The pediatrician added that more than 80% of ADHD care takes place in pediatric offices, but much of it is “badly diagnosed and poorly treated” in both primary care and specialty offices.

Jesse Hackell, MD, a private practice pediatrician in a suburb of New York City and vice president of the New York AAP Chapter 3, attended the session and agreed with Dr. Lessin that pediatricians are best suited to manage ADHD over other practitioners.

“One of the things he pointed out is that it’s a pediatric issue,” Dr. Hackell said. “We’re better at this than psychiatrists, than neurologists, than psychologists because we’re really focused on the whole lifestyle of the child, how it impacts them at home, how it impacts them at school, and how it impacts them in the social sphere.”

There’s also been a substantial increase in mental health issues as a proportion of visits, particularly recently with the pandemic and accompanying lockdowns. Youth already have limited access to mental health resources, making general pediatricians’ roles even more important. “Who else is going to provide this much needed service if not pediatricians?” Dr. Lessin asked.

Again, Dr. Hackell agreed, noting that the AAP’s toolkit is especially helpful in providing this care.

“It’s something that pediatricians have often been afraid to deal with and who farm them out to these other specialties, and I don’t think the children are served as well,” Dr. Hackell said. “If you do the right forms and questionnaires, you can actually make it work for the kids and work it for your office, which generates a lot of visits and generates revenue.”
 

Where to start

Dr. Lessin began by recommending that all pediatricians read the AAP’s clinical practice guidelines for ADHD along with its supplemental material (Process of Care Algorithm, and Systemic Barriers to Care of Children and Adolescents with ADHD).

“The first thing is you must educate yourself,” he said. “You have to learn the medicine and what are you able and comfortable doing because few of us were ever trained in our residency programs about ADHD care.”

Providers also need to learn to manage barriers to care, including referral sources and insurance company and medication hassles. Then you need to figure out how to structure the visits, determine the most appropriate visit settings, and learn to document and code appropriately. These are not quick 10-minute visits, Dr. Lessin said. Doctors must schedule enough time for them, although they may be able to do them faster with practice.

Dr. Lessin offered encouraging words for those feeling overwhelmed: “Overcome your anxiety. This is not as hard as it seems. It’s a little bit harder with comorbidities, but many chronic diseases we manage are far worse.”

In addition to reading the guidelines and review articles, seeking out mental health training programs, and learning the medications available, Dr. Lessin told attendees to get comfortable with the fact that a lot of treatment comes down to trial and error.

Again, he emphasized the value of the toolkit, which Dr. Hackell echoed.

“It’s a really nice roadmap to be able to follow and to explain how it requires two or three or four visits to treat these children well and get them started on treatment,” Dr. Hackell said. “It’s something that I recommend people use if they have not already done so to integrate ADHD care into their practices.”
 

Beginning the process

In figuring out how to structure visits, avoid addressing ADHD as a “by-the-way” issue, such as when a parent mentions it at the end of an appointment, Dr. Lessin said. Instead, start with an intake visit to determine whether you’re the right person to evaluate the child and hand out Parent and Teacher Evaluation scales to begin the process. Next, do the evaluation, discuss the process with the family, determine how treatment will work, and then look at comorbidities.

Visit settings can be traditional face-to-face visits, which are particularly helpful for intake visits, Dr. Lessin said, or telehealth, especially during the pandemic. In-person visits allow you more easily to make eye contact with the child and observe the parent and child behaviors and interactions, but telehealth often is adequate for titrating medication, discussing side effects, monitoring, and similar follow-up.

“Coding practices are absolutely necessary to make your practice viable, much less make money,” Dr. Lessin said. “Doing good for people and doing well for yourself are not mutually exclusive. You have to figure out a way to make it work economically for the practice or else you’re just not going to do it.”

He reminded pediatricians to code for evaluation, monitoring scales, and care coordination, and to be prepared for the big change of new coding rules coming in 2021.

“For better or worse, documentation is the key to survival in medical practice these days,” Dr. Lessin said. “This is true for all medical care these days, but it’s particularly true for ADHD because visits are all high intensity codes and should be coded as such.”

Templates are fine, he said, but box-checking isn’t enough; leave space for a narrative that explains the case complexity and decision-making.
 

Training staff is essential

It’s utterly essential to train all office staff, Dr. Lessin said. “I can’t tell you how important this step is because no matter how much you know or how well you understand what you want to do, you’re going to be frustrated at every turn if your staff and colleagues don’t get this stuff.”

That includes training those who make appointments, front desk staff, clinical staff, and practice colleagues regarding coding, scheduling, visit protocols, and similar procedures. Cheat sheets can be helpful here.

“They must understand the structure of the visits, what happens at each visit, the time requirements for each visit, and the standard follow-up,” including, for clinical staff, what handouts and rating scales to use, he said. “And if they aren’t sure what the parents needs or what you want, make sure they know to contact you.”

Colleagues also need to learn to properly document visits to justify coding and complexity, and not dump all patients on you.

One challenge that Dr. Lessin acknowledged as a common problem is that many pediatricians don’t have subspecialists they can refer patients to.

“Sadly, this is true almost everywhere, in rural and in big cities, near big medical centers and only local hospitals,” Dr. Lessin said. “This another reason why I think you need to learn and treat this illness to the extent you can. Your families need you.”

Dr. Hackell particularly appreciated this point, emphasizing again how important it is that pediatricians manage ADHD care of their patients.

“We see their day-to-day life, and that’s where this impacts these kids and families,” he said. “It’s really rewarding to do from my personal experience because you can really make a really big difference in these kids’ lives when they’re younger and even as they get older. When you get the rewards, it makes the work all worthwhile.”

Dr. Lessin and Dr. Hackell said they have no relevant financial disclosures.

Integrating ADHD care into practice work flows is vitally important for all practitioners who care for children, said Herschel Lessin, MD, a senior partner of the Children’s Medical Group in Poughkeepsie, N.Y.

O_Lypa/iStock/Getty Images

Although not necessarily “easy” to do, it’s far less overwhelming than it seems when doctors take the time to thoughtfully set up protocols, train others in the office, and use the ADHD Toolkit sold by the American Academy of Pediatrics, Dr. Lessin told attendees at the annual meeting of the AAP, held virtually this year. Dr. Lessin is a coeditor of the AAP’s ADHD Toolkit 3rd Ed., although he does not receive royalties from it. The toolkit includes patient handouts, clinicians tools, and rating scales that help practices incorporate ADHD care into their practices.

“The biggest complaint is: ‘But I don’t have enough time to do all of this stuff,’ ” Dr. Lessin said. “The reality is, once you’re comfortable with the visits and you know how they progress and flow, they can be done much more quickly.” He emphasized that practices can make money by integrating ADHD care into practice as long as they have a strategic plan and invest the time into training and protocols.

Dr. Lessin gave multiple reasons it’s important to integrate ADHD care into practices, starting with the condition’s prevalence and the importance of building a medical home for patients.

“ADHD affects 8%-10% of your patient population, a truly enormous number, yet many pediatricians do not treat ADHD in their practices, depriving their patients of needed care and depriving themselves from economic benefits of the visits and the revenue,” he said. The pediatrician added that more than 80% of ADHD care takes place in pediatric offices, but much of it is “badly diagnosed and poorly treated” in both primary care and specialty offices.

Jesse Hackell, MD, a private practice pediatrician in a suburb of New York City and vice president of the New York AAP Chapter 3, attended the session and agreed with Dr. Lessin that pediatricians are best suited to manage ADHD over other practitioners.

“One of the things he pointed out is that it’s a pediatric issue,” Dr. Hackell said. “We’re better at this than psychiatrists, than neurologists, than psychologists because we’re really focused on the whole lifestyle of the child, how it impacts them at home, how it impacts them at school, and how it impacts them in the social sphere.”

There’s also been a substantial increase in mental health issues as a proportion of visits, particularly recently with the pandemic and accompanying lockdowns. Youth already have limited access to mental health resources, making general pediatricians’ roles even more important. “Who else is going to provide this much needed service if not pediatricians?” Dr. Lessin asked.

Again, Dr. Hackell agreed, noting that the AAP’s toolkit is especially helpful in providing this care.

“It’s something that pediatricians have often been afraid to deal with and who farm them out to these other specialties, and I don’t think the children are served as well,” Dr. Hackell said. “If you do the right forms and questionnaires, you can actually make it work for the kids and work it for your office, which generates a lot of visits and generates revenue.”
 

Where to start

Dr. Lessin began by recommending that all pediatricians read the AAP’s clinical practice guidelines for ADHD along with its supplemental material (Process of Care Algorithm, and Systemic Barriers to Care of Children and Adolescents with ADHD).

“The first thing is you must educate yourself,” he said. “You have to learn the medicine and what are you able and comfortable doing because few of us were ever trained in our residency programs about ADHD care.”

Providers also need to learn to manage barriers to care, including referral sources and insurance company and medication hassles. Then you need to figure out how to structure the visits, determine the most appropriate visit settings, and learn to document and code appropriately. These are not quick 10-minute visits, Dr. Lessin said. Doctors must schedule enough time for them, although they may be able to do them faster with practice.

Dr. Lessin offered encouraging words for those feeling overwhelmed: “Overcome your anxiety. This is not as hard as it seems. It’s a little bit harder with comorbidities, but many chronic diseases we manage are far worse.”

In addition to reading the guidelines and review articles, seeking out mental health training programs, and learning the medications available, Dr. Lessin told attendees to get comfortable with the fact that a lot of treatment comes down to trial and error.

Again, he emphasized the value of the toolkit, which Dr. Hackell echoed.

“It’s a really nice roadmap to be able to follow and to explain how it requires two or three or four visits to treat these children well and get them started on treatment,” Dr. Hackell said. “It’s something that I recommend people use if they have not already done so to integrate ADHD care into their practices.”
 

Beginning the process

In figuring out how to structure visits, avoid addressing ADHD as a “by-the-way” issue, such as when a parent mentions it at the end of an appointment, Dr. Lessin said. Instead, start with an intake visit to determine whether you’re the right person to evaluate the child and hand out Parent and Teacher Evaluation scales to begin the process. Next, do the evaluation, discuss the process with the family, determine how treatment will work, and then look at comorbidities.

Visit settings can be traditional face-to-face visits, which are particularly helpful for intake visits, Dr. Lessin said, or telehealth, especially during the pandemic. In-person visits allow you more easily to make eye contact with the child and observe the parent and child behaviors and interactions, but telehealth often is adequate for titrating medication, discussing side effects, monitoring, and similar follow-up.

“Coding practices are absolutely necessary to make your practice viable, much less make money,” Dr. Lessin said. “Doing good for people and doing well for yourself are not mutually exclusive. You have to figure out a way to make it work economically for the practice or else you’re just not going to do it.”

He reminded pediatricians to code for evaluation, monitoring scales, and care coordination, and to be prepared for the big change of new coding rules coming in 2021.

“For better or worse, documentation is the key to survival in medical practice these days,” Dr. Lessin said. “This is true for all medical care these days, but it’s particularly true for ADHD because visits are all high intensity codes and should be coded as such.”

Templates are fine, he said, but box-checking isn’t enough; leave space for a narrative that explains the case complexity and decision-making.
 

Training staff is essential

It’s utterly essential to train all office staff, Dr. Lessin said. “I can’t tell you how important this step is because no matter how much you know or how well you understand what you want to do, you’re going to be frustrated at every turn if your staff and colleagues don’t get this stuff.”

That includes training those who make appointments, front desk staff, clinical staff, and practice colleagues regarding coding, scheduling, visit protocols, and similar procedures. Cheat sheets can be helpful here.

“They must understand the structure of the visits, what happens at each visit, the time requirements for each visit, and the standard follow-up,” including, for clinical staff, what handouts and rating scales to use, he said. “And if they aren’t sure what the parents needs or what you want, make sure they know to contact you.”

Colleagues also need to learn to properly document visits to justify coding and complexity, and not dump all patients on you.

One challenge that Dr. Lessin acknowledged as a common problem is that many pediatricians don’t have subspecialists they can refer patients to.

“Sadly, this is true almost everywhere, in rural and in big cities, near big medical centers and only local hospitals,” Dr. Lessin said. “This another reason why I think you need to learn and treat this illness to the extent you can. Your families need you.”

Dr. Hackell particularly appreciated this point, emphasizing again how important it is that pediatricians manage ADHD care of their patients.

“We see their day-to-day life, and that’s where this impacts these kids and families,” he said. “It’s really rewarding to do from my personal experience because you can really make a really big difference in these kids’ lives when they’re younger and even as they get older. When you get the rewards, it makes the work all worthwhile.”

Dr. Lessin and Dr. Hackell said they have no relevant financial disclosures.

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Overall Grand Prize
Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum

Anthony K. Guzman, MD; Jessica L. Garelik, DO; Steven R. Cohen, MD, MPH, Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, New York 
Disclosures: None. 

Background 
Molluscum contagiosum (MC) is a common cutaneous infection caused by a DNA poxvirus, predominantly affecting children. There is a paucity of high-quality evidence on which to make clinical decisions in treating MC.¹ Cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly used treatment for this condition. However, despite the prevalence of its use, cantharidin is not approved by the US Food and Drug Administration, is not standardized in formulation or treatment regimen, and is not always manufactured in accordance with good manufacturing practice (GMP), leading to a lack of commercial availability.^2,3

Objective 
To determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under GMP for the treatment of MC.

Methods 
We conducted a 12-week, open-label pilot trial at a single outpatient dermatology clinic. Patients aged 2 to 17 years (N=30) with a clinical diagnosis of MC and fewer than 50 lesions were included. Patients were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under GMP (VP-102), applied with the wooden end of a cotton swab approximately every 21 days for up to 4 treatments or until complete lesion clearance. Patients were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if notable blistering occurred. Lesion counts and adverse events, including local skin reactions, were documented at each visit. Quality of life also was measured using the Children’s Dermatology Quality of Life Index at baseline and at the end of study (EOS). The primary end point was the percentage of patients achieving total clearance by EOS on day 84. 

Results 
The mean patient age was 5.8 years (range, 2–12 years). A total of 26 patients (86.7%) experienced at least 1 expected local skin reaction, such as blistering or erythema. No serious or unexpected treatment-related adverse events were encountered. A total of 25 patients pooled from both cohorts completed the study. Eleven patients (44.0%) achieved total lesion clearance by EOS. The mean (standard deviation) lesion count was significantly reduced from 23.0 (15.6) at baseline to 6.8 (11.7) at EOS (P<.0001). The mean (standard deviation) Children’s Dermatology Quality of Life Index score was markedly improved from 3.9 (5.6) at baseline to 0.38 (1.3) at EOS (P=.01).

Conclusions 
VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients.

References

1. van der Wouden JC, van der Sande R, Kruithof EJ, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017;5:CD004767.
2. Coloe J, Morrell DS. Cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. Pediatr Dermatol. 2009;26:405-408.
3. Pompei DT, Rezzadeh KS, Viola KV, et al. Cantharidin therapy: practice patterns and attitudes of health care providers. J Am Acad Dermatol. 2013;68:1045-1046.

Up next: Autologous cell therapy for recessive dystrophic epidermolysis bullosa

Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa

Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California;  Tufts University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm²) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.

Up next: Skin toxicity in metastatic melanoma patients treated with ICIs

Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None. 

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.

Up next: Risk of COVID-19 in patients receiving immunobiologic therapy

Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
Disclosures: None. 

Importance
Data on the risks of immunosuppressive biologics in the context of coronavirus disease 2019 (COVID-19) infection are limited, creating uncertainty for patients and providers whether to continue therapy during the pandemic.

Objective
To investigate whether patients treated with biologics were at an increased risk for COVID-19 infection as well as all-cause mortality once infected. 

Design
A multicenter retrospective study of 7361 patients prescribed biologics and 74,910 matched controls, cross-referenced with COVID-19 infection and all-cause mortality data through June 19, 2020, from the Massachusetts Department of Public Health.

Participants 
Patients with at least 1 prescription for an immunosuppressive biologic in the Mass General Brigham health care system between July 1, 2019, and February 29, 2020. Multivariate logistic regression was used on matched data to calculate the odds ratio (OR) for COVID-19 infection status between patients on biologics and controls, adjusting for age, gender, race, Charlson Comorbidity index (CCI) severity grade, median income, and local infection rate. An analysis adjusting for individual comorbidities was also performed. Multivariate Poisson regression was performed on COVID-19 positive patients to compare the risk for all-cause mortality, adjusting for gender, CCI severity grade, median income, and local COVID-19 rate.

Setting 
Retrospective matched cohort.

Exposure 
Biologic immunosuppressants.

Main Outcomes and Measures 
Odds of COVID-19 diagnosis and all-cause mortality following the diagnosis.

Results 
7,361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women, 84.5% white; mean age-adjusted CCI 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at significantly increased risk of COVID-19 diagnosis (OR 0.88, 95% CI 0.71-1.09; P=.25) or subsequent mortality (OR 1.26, 95% CI 0.57-2.76; P=.57). 

A total of 7361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women and 84.5% white; mean age-adjusted CCI, 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics, and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at increased risk for COVID-19 diagnosis (OR, 0.88; 95% CI, 0.71-1.09; P=.25) or subsequent mortality (OR 1.26; 95% CI 0.57-2.76; P=.57). 

Conclusions and Relevance 
Given an absence of evidence that patients treated with biologics are more susceptible to COVID-19, patients should be encouraged to continue their therapy to prevent disease progression during this pandemic.

Up next: Compliance With Systemic Medications for AD and Psoriasis

Importance
The management of moderate to severe atopic dermatitis (AD) is being revolutionized by the development of novel systemic therapeutics. However, these new therapeutics are being implemented using the same treatment paradigms that are used for psoriasis treatment (ie, patients on systemic medications require indefinite therapy). While use of systemic therapeutics indefinitely is acceptable to many psoriasis patients because psoriasis severity is frequently stable over long periods of time, AD is hallmarked by seasonal flares followed by periods of relative quiescence, making indefinite therapy less attractive to patients with AD. 

Objective
This whole-population cohort study describes systemic medication adherence patterns in AD and psoriasis patients. These patterns are then compared to determine whether systemic medications requiring indefinite therapy are adhered to at similar rates in the AD and psoriasis populations. The aim of this comparison is to assess whether drugs requiring indefinite therapy meet the needs of AD patients requiring systemic treatment.

Design, Setting, and Participants 
This is a retrospective cohort study using the national Veterans Administration (VA) health database to identify all veterans with psoriasis and AD who are receiving care at any VA location. Veterans with psoriasis and AD were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Veterans were included in the study if they received nonsteroidal systemic immunosuppressive or immunomodulatory medications for their psoriasis or AD. 

Main Outcome(s) and Measure(s)
All medications filled at a VA pharmacy are time stamped. This unique data recording allows for real-world adherence to be evaluated by comparing actual medication fill dates to expected medication fill dates based on refill interval. Patients who fill a medication more than 7 days after the expected refill date are classified as nonadherent. We described systemic medication adherence rates and assessed for seasonal variation in adherence patterns for AD and psoriasis patients. Cofounding variables, including history of mental illness, substance use disorder, and patient income, were recorded and included in the analysis. 

Conclusions and Relevance 

This study's unique data source provides insight into the ways adherence patterns differ between individuals with AD and psoriasis, and insights into the ways mental illness, substance use, and poverty affect adherence to systemic therapeutics among dermatology patients with inflammatory skin conditions. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Overall Grand Prize
Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum

Anthony K. Guzman, MD; Jessica L. Garelik, DO; Steven R. Cohen, MD, MPH, Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, New York 
Disclosures: None. 

Background 
Molluscum contagiosum (MC) is a common cutaneous infection caused by a DNA poxvirus, predominantly affecting children. There is a paucity of high-quality evidence on which to make clinical decisions in treating MC.¹ Cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly used treatment for this condition. However, despite the prevalence of its use, cantharidin is not approved by the US Food and Drug Administration, is not standardized in formulation or treatment regimen, and is not always manufactured in accordance with good manufacturing practice (GMP), leading to a lack of commercial availability.^2,3

Objective 
To determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under GMP for the treatment of MC.

Methods 
We conducted a 12-week, open-label pilot trial at a single outpatient dermatology clinic. Patients aged 2 to 17 years (N=30) with a clinical diagnosis of MC and fewer than 50 lesions were included. Patients were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under GMP (VP-102), applied with the wooden end of a cotton swab approximately every 21 days for up to 4 treatments or until complete lesion clearance. Patients were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if notable blistering occurred. Lesion counts and adverse events, including local skin reactions, were documented at each visit. Quality of life also was measured using the Children’s Dermatology Quality of Life Index at baseline and at the end of study (EOS). The primary end point was the percentage of patients achieving total clearance by EOS on day 84. 

Results 
The mean patient age was 5.8 years (range, 2–12 years). A total of 26 patients (86.7%) experienced at least 1 expected local skin reaction, such as blistering or erythema. No serious or unexpected treatment-related adverse events were encountered. A total of 25 patients pooled from both cohorts completed the study. Eleven patients (44.0%) achieved total lesion clearance by EOS. The mean (standard deviation) lesion count was significantly reduced from 23.0 (15.6) at baseline to 6.8 (11.7) at EOS (P<.0001). The mean (standard deviation) Children’s Dermatology Quality of Life Index score was markedly improved from 3.9 (5.6) at baseline to 0.38 (1.3) at EOS (P=.01).

Conclusions 
VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients.

References

1. van der Wouden JC, van der Sande R, Kruithof EJ, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017;5:CD004767.
2. Coloe J, Morrell DS. Cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. Pediatr Dermatol. 2009;26:405-408.
3. Pompei DT, Rezzadeh KS, Viola KV, et al. Cantharidin therapy: practice patterns and attitudes of health care providers. J Am Acad Dermatol. 2013;68:1045-1046.

Up next: Autologous cell therapy for recessive dystrophic epidermolysis bullosa

Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa

Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California;  Tufts University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm²) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.

Up next: Skin toxicity in metastatic melanoma patients treated with ICIs

Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None. 

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.

Up next: Risk of COVID-19 in patients receiving immunobiologic therapy

Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
Disclosures: None. 

Importance
Data on the risks of immunosuppressive biologics in the context of coronavirus disease 2019 (COVID-19) infection are limited, creating uncertainty for patients and providers whether to continue therapy during the pandemic.

Objective
To investigate whether patients treated with biologics were at an increased risk for COVID-19 infection as well as all-cause mortality once infected. 

Design
A multicenter retrospective study of 7361 patients prescribed biologics and 74,910 matched controls, cross-referenced with COVID-19 infection and all-cause mortality data through June 19, 2020, from the Massachusetts Department of Public Health.

Participants 
Patients with at least 1 prescription for an immunosuppressive biologic in the Mass General Brigham health care system between July 1, 2019, and February 29, 2020. Multivariate logistic regression was used on matched data to calculate the odds ratio (OR) for COVID-19 infection status between patients on biologics and controls, adjusting for age, gender, race, Charlson Comorbidity index (CCI) severity grade, median income, and local infection rate. An analysis adjusting for individual comorbidities was also performed. Multivariate Poisson regression was performed on COVID-19 positive patients to compare the risk for all-cause mortality, adjusting for gender, CCI severity grade, median income, and local COVID-19 rate.

Setting 
Retrospective matched cohort.

Exposure 
Biologic immunosuppressants.

Main Outcomes and Measures 
Odds of COVID-19 diagnosis and all-cause mortality following the diagnosis.

Results 
7,361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women, 84.5% white; mean age-adjusted CCI 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at significantly increased risk of COVID-19 diagnosis (OR 0.88, 95% CI 0.71-1.09; P=.25) or subsequent mortality (OR 1.26, 95% CI 0.57-2.76; P=.57). 

A total of 7361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women and 84.5% white; mean age-adjusted CCI, 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics, and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at increased risk for COVID-19 diagnosis (OR, 0.88; 95% CI, 0.71-1.09; P=.25) or subsequent mortality (OR 1.26; 95% CI 0.57-2.76; P=.57). 

Conclusions and Relevance 
Given an absence of evidence that patients treated with biologics are more susceptible to COVID-19, patients should be encouraged to continue their therapy to prevent disease progression during this pandemic.

Up next: Compliance With Systemic Medications for AD and Psoriasis

Importance
The management of moderate to severe atopic dermatitis (AD) is being revolutionized by the development of novel systemic therapeutics. However, these new therapeutics are being implemented using the same treatment paradigms that are used for psoriasis treatment (ie, patients on systemic medications require indefinite therapy). While use of systemic therapeutics indefinitely is acceptable to many psoriasis patients because psoriasis severity is frequently stable over long periods of time, AD is hallmarked by seasonal flares followed by periods of relative quiescence, making indefinite therapy less attractive to patients with AD. 

Objective
This whole-population cohort study describes systemic medication adherence patterns in AD and psoriasis patients. These patterns are then compared to determine whether systemic medications requiring indefinite therapy are adhered to at similar rates in the AD and psoriasis populations. The aim of this comparison is to assess whether drugs requiring indefinite therapy meet the needs of AD patients requiring systemic treatment.

Design, Setting, and Participants 
This is a retrospective cohort study using the national Veterans Administration (VA) health database to identify all veterans with psoriasis and AD who are receiving care at any VA location. Veterans with psoriasis and AD were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Veterans were included in the study if they received nonsteroidal systemic immunosuppressive or immunomodulatory medications for their psoriasis or AD. 

Main Outcome(s) and Measure(s)
All medications filled at a VA pharmacy are time stamped. This unique data recording allows for real-world adherence to be evaluated by comparing actual medication fill dates to expected medication fill dates based on refill interval. Patients who fill a medication more than 7 days after the expected refill date are classified as nonadherent. We described systemic medication adherence rates and assessed for seasonal variation in adherence patterns for AD and psoriasis patients. Cofounding variables, including history of mental illness, substance use disorder, and patient income, were recorded and included in the analysis. 

Conclusions and Relevance 

This study's unique data source provides insight into the ways adherence patterns differ between individuals with AD and psoriasis, and insights into the ways mental illness, substance use, and poverty affect adherence to systemic therapeutics among dermatology patients with inflammatory skin conditions. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Overall Grand Prize
Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum

Anthony K. Guzman, MD; Jessica L. Garelik, DO; Steven R. Cohen, MD, MPH, Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, New York 
Disclosures: None. 

Background 
Molluscum contagiosum (MC) is a common cutaneous infection caused by a DNA poxvirus, predominantly affecting children. There is a paucity of high-quality evidence on which to make clinical decisions in treating MC.¹ Cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly used treatment for this condition. However, despite the prevalence of its use, cantharidin is not approved by the US Food and Drug Administration, is not standardized in formulation or treatment regimen, and is not always manufactured in accordance with good manufacturing practice (GMP), leading to a lack of commercial availability.^2,3

Objective 
To determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under GMP for the treatment of MC.

Methods 
We conducted a 12-week, open-label pilot trial at a single outpatient dermatology clinic. Patients aged 2 to 17 years (N=30) with a clinical diagnosis of MC and fewer than 50 lesions were included. Patients were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under GMP (VP-102), applied with the wooden end of a cotton swab approximately every 21 days for up to 4 treatments or until complete lesion clearance. Patients were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if notable blistering occurred. Lesion counts and adverse events, including local skin reactions, were documented at each visit. Quality of life also was measured using the Children’s Dermatology Quality of Life Index at baseline and at the end of study (EOS). The primary end point was the percentage of patients achieving total clearance by EOS on day 84. 

Results 
The mean patient age was 5.8 years (range, 2–12 years). A total of 26 patients (86.7%) experienced at least 1 expected local skin reaction, such as blistering or erythema. No serious or unexpected treatment-related adverse events were encountered. A total of 25 patients pooled from both cohorts completed the study. Eleven patients (44.0%) achieved total lesion clearance by EOS. The mean (standard deviation) lesion count was significantly reduced from 23.0 (15.6) at baseline to 6.8 (11.7) at EOS (P<.0001). The mean (standard deviation) Children’s Dermatology Quality of Life Index score was markedly improved from 3.9 (5.6) at baseline to 0.38 (1.3) at EOS (P=.01).

Conclusions 
VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients.

References

1. van der Wouden JC, van der Sande R, Kruithof EJ, et al. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2017;5:CD004767.
2. Coloe J, Morrell DS. Cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. Pediatr Dermatol. 2009;26:405-408.
3. Pompei DT, Rezzadeh KS, Viola KV, et al. Cantharidin therapy: practice patterns and attitudes of health care providers. J Am Acad Dermatol. 2013;68:1045-1046.

Up next: Autologous cell therapy for recessive dystrophic epidermolysis bullosa

Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa

Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California;  Tufts University Medical Center, Boston, Massachusetts 
Disclosures: None. 

Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm²) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.

Up next: Skin toxicity in metastatic melanoma patients treated with ICIs

Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York
Disclosures: None. 

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with metastatic melanoma, but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed metastatic melanoma patients enrolled prospectively in a clinicopathological database with protocol-driven follow-up and treated with ICI. We tested the associations between developing ST, stratified as none (n=257), mild (n=86), and severe (n=44), and progression-free survival (PFS) and overall survival in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival leading to adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Mild ST was significantly associated with improved PFS and overall survival (P=.001 and P=.018, respectively) in univariable analysis and with improved PFS in multivariable analysis (P=.020). However, these associations lost significance after adjusting for the time from treatment initiation to time of skin event (P>.05). Severe ST was not associated with improved outcomes. Our data reveal the influence of event severity and time to event as covariates in analyzing the relationship between ST and ICI outcomes. Further, we reinforce the importance of identifying baseline predictors of response and toxicity to ICI to optimize treatment selection and prophylactic care when indicated.

Up next: Risk of COVID-19 in patients receiving immunobiologic therapy

Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
Disclosures: None. 

Importance
Data on the risks of immunosuppressive biologics in the context of coronavirus disease 2019 (COVID-19) infection are limited, creating uncertainty for patients and providers whether to continue therapy during the pandemic.

Objective
To investigate whether patients treated with biologics were at an increased risk for COVID-19 infection as well as all-cause mortality once infected. 

Design
A multicenter retrospective study of 7361 patients prescribed biologics and 74,910 matched controls, cross-referenced with COVID-19 infection and all-cause mortality data through June 19, 2020, from the Massachusetts Department of Public Health.

Participants 
Patients with at least 1 prescription for an immunosuppressive biologic in the Mass General Brigham health care system between July 1, 2019, and February 29, 2020. Multivariate logistic regression was used on matched data to calculate the odds ratio (OR) for COVID-19 infection status between patients on biologics and controls, adjusting for age, gender, race, Charlson Comorbidity index (CCI) severity grade, median income, and local infection rate. An analysis adjusting for individual comorbidities was also performed. Multivariate Poisson regression was performed on COVID-19 positive patients to compare the risk for all-cause mortality, adjusting for gender, CCI severity grade, median income, and local COVID-19 rate.

Setting 
Retrospective matched cohort.

Exposure 
Biologic immunosuppressants.

Main Outcomes and Measures 
Odds of COVID-19 diagnosis and all-cause mortality following the diagnosis.

Results 
7,361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women, 84.5% white; mean age-adjusted CCI 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at significantly increased risk of COVID-19 diagnosis (OR 0.88, 95% CI 0.71-1.09; P=.25) or subsequent mortality (OR 1.26, 95% CI 0.57-2.76; P=.57). 

A total of 7361 patients treated with biologics and 74,910 matched controls were included in the analysis (mean age, 50.6 years; 56.0% women and 84.5% white; mean age-adjusted CCI, 2.8). There were 87 (1.2%) infections and 7 deaths (8.0%) in patients treated with biologics, and 1063 (1.4%) infections and 71 deaths (6.7%) in the control group. Patients treated with immunosuppressive biologics were not at increased risk for COVID-19 diagnosis (OR, 0.88; 95% CI, 0.71-1.09; P=.25) or subsequent mortality (OR 1.26; 95% CI 0.57-2.76; P=.57). 

Conclusions and Relevance 
Given an absence of evidence that patients treated with biologics are more susceptible to COVID-19, patients should be encouraged to continue their therapy to prevent disease progression during this pandemic.

Up next: Compliance With Systemic Medications for AD and Psoriasis

Importance
The management of moderate to severe atopic dermatitis (AD) is being revolutionized by the development of novel systemic therapeutics. However, these new therapeutics are being implemented using the same treatment paradigms that are used for psoriasis treatment (ie, patients on systemic medications require indefinite therapy). While use of systemic therapeutics indefinitely is acceptable to many psoriasis patients because psoriasis severity is frequently stable over long periods of time, AD is hallmarked by seasonal flares followed by periods of relative quiescence, making indefinite therapy less attractive to patients with AD. 

Objective
This whole-population cohort study describes systemic medication adherence patterns in AD and psoriasis patients. These patterns are then compared to determine whether systemic medications requiring indefinite therapy are adhered to at similar rates in the AD and psoriasis populations. The aim of this comparison is to assess whether drugs requiring indefinite therapy meet the needs of AD patients requiring systemic treatment.

Design, Setting, and Participants 
This is a retrospective cohort study using the national Veterans Administration (VA) health database to identify all veterans with psoriasis and AD who are receiving care at any VA location. Veterans with psoriasis and AD were identified using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Veterans were included in the study if they received nonsteroidal systemic immunosuppressive or immunomodulatory medications for their psoriasis or AD. 

Main Outcome(s) and Measure(s)
All medications filled at a VA pharmacy are time stamped. This unique data recording allows for real-world adherence to be evaluated by comparing actual medication fill dates to expected medication fill dates based on refill interval. Patients who fill a medication more than 7 days after the expected refill date are classified as nonadherent. We described systemic medication adherence rates and assessed for seasonal variation in adherence patterns for AD and psoriasis patients. Cofounding variables, including history of mental illness, substance use disorder, and patient income, were recorded and included in the analysis. 

Conclusions and Relevance 

This study's unique data source provides insight into the ways adherence patterns differ between individuals with AD and psoriasis, and insights into the ways mental illness, substance use, and poverty affect adherence to systemic therapeutics among dermatology patients with inflammatory skin conditions. 

 
The dermMentors™ Resident of Distinction Award™ was presented to 5 dermatology residents at the virtual 16th Annual Coastal Dermatology Symposium, October 15–16, 2020. Recipients of the award include Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California, and  Tufts University Medical Center, Boston, Massachusetts; Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York; Anthony K. Guzman, MD, Albert Einstein College of Medicine, Bronx, New York; Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts; and Reid Waldman, MD, University of Connecticut, Farmington. The residents presented their research during the general sessions on October 16, 2020.

The overall grand prize was awarded to Dr. Guzman for his research entitled, “Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum.” Dr. Guzman presented the results of a 12-week, open-label pilot trial at a single outpatient dermatology clinic to determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under good manufacturing practice for the treatment of molluscum contagiosum. “VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients,” Dr. Guzman reported.

Presentations by the other residents included results of a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa (Dr. Eichstadt), an analysis of the association between skin toxicity and better response in melanoma patients treated with immune checkpoint inhibitors (Dr. Gulati), a study of the risks of COVID-19 infection and mortality for patients on biologics (Dr. Klebanov), and a comparison of compliance rates of atopic dermatitis patients on systemic medications with those of psoriasis patients on systemic medications (Dr. Waldman). Access all of the abstracts presented by the top residents here. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

 
The dermMentors™ Resident of Distinction Award™ was presented to 5 dermatology residents at the virtual 16th Annual Coastal Dermatology Symposium, October 15–16, 2020. Recipients of the award include Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California, and  Tufts University Medical Center, Boston, Massachusetts; Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York; Anthony K. Guzman, MD, Albert Einstein College of Medicine, Bronx, New York; Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts; and Reid Waldman, MD, University of Connecticut, Farmington. The residents presented their research during the general sessions on October 16, 2020.

The overall grand prize was awarded to Dr. Guzman for his research entitled, “Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum.” Dr. Guzman presented the results of a 12-week, open-label pilot trial at a single outpatient dermatology clinic to determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under good manufacturing practice for the treatment of molluscum contagiosum. “VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients,” Dr. Guzman reported.

Presentations by the other residents included results of a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa (Dr. Eichstadt), an analysis of the association between skin toxicity and better response in melanoma patients treated with immune checkpoint inhibitors (Dr. Gulati), a study of the risks of COVID-19 infection and mortality for patients on biologics (Dr. Klebanov), and a comparison of compliance rates of atopic dermatitis patients on systemic medications with those of psoriasis patients on systemic medications (Dr. Waldman). Access all of the abstracts presented by the top residents here. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

 
The dermMentors™ Resident of Distinction Award™ was presented to 5 dermatology residents at the virtual 16th Annual Coastal Dermatology Symposium, October 15–16, 2020. Recipients of the award include Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California, and  Tufts University Medical Center, Boston, Massachusetts; Nicholas Gulati, MD, PhD, NYU Grossman School of Medicine, New York, New York; Anthony K. Guzman, MD, Albert Einstein College of Medicine, Bronx, New York; Nikolai Klebanov, MD, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts; and Reid Waldman, MD, University of Connecticut, Farmington. The residents presented their research during the general sessions on October 16, 2020.

The overall grand prize was awarded to Dr. Guzman for his research entitled, “Topical Cantharidin Revisited: A Phase 2 Study Investigating a Commercially Viable Formulation of Cantharidin (VP-102) for the Treatment of Molluscum Contagiosum.” Dr. Guzman presented the results of a 12-week, open-label pilot trial at a single outpatient dermatology clinic to determine the efficacy and safety of VP-102, a novel, standardized, commercially viable cantharidin formulation produced under good manufacturing practice for the treatment of molluscum contagiosum. “VP-102 was well tolerated with either a 6- or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life, and complete clearance of MC lesions in nearly half of the patients,” Dr. Guzman reported.

Presentations by the other residents included results of a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa (Dr. Eichstadt), an analysis of the association between skin toxicity and better response in melanoma patients treated with immune checkpoint inhibitors (Dr. Gulati), a study of the risks of COVID-19 infection and mortality for patients on biologics (Dr. Klebanov), and a comparison of compliance rates of atopic dermatitis patients on systemic medications with those of psoriasis patients on systemic medications (Dr. Waldman). Access all of the abstracts presented by the top residents here. 

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2020 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the virtual 16th Annual Coastal Dermatology Symposium on October 16, 2020.

Disparities driven by socioeconomic factors have been shown to affect outcomes for patients with a variety of cancer types. Researchers found that this was also true for patients with multiple myeloma, according to a report published in Hematology/Oncology and Stem Cell Therapy.

In particular, survival was affected by a variety of socioeconomic factors.

Researchers conducting the study queried the National Cancer Database for patients diagnosed with multiple myeloma between 2004 and 2016. Only those 56,102 patients who received systemic therapy as the first-line treatment were included, according to Thejus T. Jayakrishnan, MD, of Allegheny Health Network, Pittsburgh, and colleagues.

Enrollment rates for therapy were calculated using receiving systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator). The incident rate ratios were analyzed using Poisson regression. A multivariate Cox proportional hazards model was used for survival analysis of 50,543 patients, and differences were determined as hazard ratios.

Significant differences

The study showed that therapy enrollment was significantly affected by race and sex (P < .005), with the enrollment rate for women and for non-Hispanic Blacks both being lower versus men and non-Hispanic Whites, respectively.

Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were found to be associated with poor survival (HR >1), whereas being a woman or a non-Hispanic Black (who were speculated to have more favorable cytogenetic profiles), having a higher income, and having treatment at an academic center were all associated with improved survival (each category at HR <1).

“Disparities in [multiple myeloma] exist and are caused by a complex interplay of multiple factors, with socioeconomic factors such as insurance and income playing a dominant role. The disparities not only exact high human cost but also negatively impact the economics of health care,” the researchers concluded.

The study was not funded and the authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Jayakrishnan TT et al. Hematol Oncol Stem Cell Ther. 2020 Oct 10. doi: 10.1016/j.hemonc.2020.09.005.

Disparities driven by socioeconomic factors have been shown to affect outcomes for patients with a variety of cancer types. Researchers found that this was also true for patients with multiple myeloma, according to a report published in Hematology/Oncology and Stem Cell Therapy.

In particular, survival was affected by a variety of socioeconomic factors.

Researchers conducting the study queried the National Cancer Database for patients diagnosed with multiple myeloma between 2004 and 2016. Only those 56,102 patients who received systemic therapy as the first-line treatment were included, according to Thejus T. Jayakrishnan, MD, of Allegheny Health Network, Pittsburgh, and colleagues.

Enrollment rates for therapy were calculated using receiving systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator). The incident rate ratios were analyzed using Poisson regression. A multivariate Cox proportional hazards model was used for survival analysis of 50,543 patients, and differences were determined as hazard ratios.

Significant differences

The study showed that therapy enrollment was significantly affected by race and sex (P < .005), with the enrollment rate for women and for non-Hispanic Blacks both being lower versus men and non-Hispanic Whites, respectively.

Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were found to be associated with poor survival (HR >1), whereas being a woman or a non-Hispanic Black (who were speculated to have more favorable cytogenetic profiles), having a higher income, and having treatment at an academic center were all associated with improved survival (each category at HR <1).

“Disparities in [multiple myeloma] exist and are caused by a complex interplay of multiple factors, with socioeconomic factors such as insurance and income playing a dominant role. The disparities not only exact high human cost but also negatively impact the economics of health care,” the researchers concluded.

The study was not funded and the authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Jayakrishnan TT et al. Hematol Oncol Stem Cell Ther. 2020 Oct 10. doi: 10.1016/j.hemonc.2020.09.005.

Disparities driven by socioeconomic factors have been shown to affect outcomes for patients with a variety of cancer types. Researchers found that this was also true for patients with multiple myeloma, according to a report published in Hematology/Oncology and Stem Cell Therapy.

In particular, survival was affected by a variety of socioeconomic factors.

Researchers conducting the study queried the National Cancer Database for patients diagnosed with multiple myeloma between 2004 and 2016. Only those 56,102 patients who received systemic therapy as the first-line treatment were included, according to Thejus T. Jayakrishnan, MD, of Allegheny Health Network, Pittsburgh, and colleagues.

Enrollment rates for therapy were calculated using receiving systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator). The incident rate ratios were analyzed using Poisson regression. A multivariate Cox proportional hazards model was used for survival analysis of 50,543 patients, and differences were determined as hazard ratios.

Significant differences

The study showed that therapy enrollment was significantly affected by race and sex (P < .005), with the enrollment rate for women and for non-Hispanic Blacks both being lower versus men and non-Hispanic Whites, respectively.

Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were found to be associated with poor survival (HR >1), whereas being a woman or a non-Hispanic Black (who were speculated to have more favorable cytogenetic profiles), having a higher income, and having treatment at an academic center were all associated with improved survival (each category at HR <1).

“Disparities in [multiple myeloma] exist and are caused by a complex interplay of multiple factors, with socioeconomic factors such as insurance and income playing a dominant role. The disparities not only exact high human cost but also negatively impact the economics of health care,” the researchers concluded.

The study was not funded and the authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Jayakrishnan TT et al. Hematol Oncol Stem Cell Ther. 2020 Oct 10. doi: 10.1016/j.hemonc.2020.09.005.

Although it appeared that the hair loss was preceded by some dry skin, the patch of hair loss was smooth and nonscarring, consistent with a diagnosis of alopecia areata (AA).

AA typically is found on the scalp in solitary areas but can affect the whole body, including the eyelashes and eyebrows. Affected hair typically is narrower at the proximal end, resembling an exclamation point, as the hair fails to grow and falls out. Sometimes, patches of alopecia may coalesce into a larger area. Nail changes may be noted, as well. Nails may become brittle, with pitting and/or longitudinal ridges. Patients are usually asymptomatic but may complain of pruritus.

AA is believed to be an autoimmune disorder. It affects males and females of all ages but is more common in children and young adults. AA is believed to result from a T-cell–mediated immune response that transitions the hair follicles from the growth phase to the resting phase. This leads to sudden hair loss and inhibition of regrowth of the hair. However, the hair follicle is not permanently destroyed as in other processes of alopecia. There is also an association between AA and other autoimmune disorders such as vitiligo, thyroid disease, and lupus.

The diagnosis usually is made clinically, as in this patient, but a definitive diagnosis can be made by biopsy and pathology. Other differential diagnoses to consider are trichotillomania, tinea, traumatic alopecia, and lupus.

In almost half of cases, AA is self-resolving; therefore, in first episodes of localized disease, watchful waiting is appropriate. Treatment is tailored to the individual patient and may be difficult. Intralesional corticosteroids often are used for mild cases. Typically, 10 mg/mL of a glucocorticoid is injected into the mid-dermis every 4 to 6 weeks; however, this treatment carries a risk of transient or even permanent atrophy of the injection site. Potent topical corticosteroids often are used, especially in children who do not tolerate intralesional injections, and success can be variable. Other topical treatments to consider are photochemotherapy (psoralen plus UVA), or an irritant agent such as anthralin and a vasodilator such as minoxidil. Regrowth can be expected in a few months to a year, but recurrence is common.

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Image courtesy of Stacy Nguy, MD, and text courtesy of Stacy Nguy, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Although it appeared that the hair loss was preceded by some dry skin, the patch of hair loss was smooth and nonscarring, consistent with a diagnosis of alopecia areata (AA).

AA typically is found on the scalp in solitary areas but can affect the whole body, including the eyelashes and eyebrows. Affected hair typically is narrower at the proximal end, resembling an exclamation point, as the hair fails to grow and falls out. Sometimes, patches of alopecia may coalesce into a larger area. Nail changes may be noted, as well. Nails may become brittle, with pitting and/or longitudinal ridges. Patients are usually asymptomatic but may complain of pruritus.

AA is believed to be an autoimmune disorder. It affects males and females of all ages but is more common in children and young adults. AA is believed to result from a T-cell–mediated immune response that transitions the hair follicles from the growth phase to the resting phase. This leads to sudden hair loss and inhibition of regrowth of the hair. However, the hair follicle is not permanently destroyed as in other processes of alopecia. There is also an association between AA and other autoimmune disorders such as vitiligo, thyroid disease, and lupus.

The diagnosis usually is made clinically, as in this patient, but a definitive diagnosis can be made by biopsy and pathology. Other differential diagnoses to consider are trichotillomania, tinea, traumatic alopecia, and lupus.

In almost half of cases, AA is self-resolving; therefore, in first episodes of localized disease, watchful waiting is appropriate. Treatment is tailored to the individual patient and may be difficult. Intralesional corticosteroids often are used for mild cases. Typically, 10 mg/mL of a glucocorticoid is injected into the mid-dermis every 4 to 6 weeks; however, this treatment carries a risk of transient or even permanent atrophy of the injection site. Potent topical corticosteroids often are used, especially in children who do not tolerate intralesional injections, and success can be variable. Other topical treatments to consider are photochemotherapy (psoralen plus UVA), or an irritant agent such as anthralin and a vasodilator such as minoxidil. Regrowth can be expected in a few months to a year, but recurrence is common.

‌

Image courtesy of Stacy Nguy, MD, and text courtesy of Stacy Nguy, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Although it appeared that the hair loss was preceded by some dry skin, the patch of hair loss was smooth and nonscarring, consistent with a diagnosis of alopecia areata (AA).

AA typically is found on the scalp in solitary areas but can affect the whole body, including the eyelashes and eyebrows. Affected hair typically is narrower at the proximal end, resembling an exclamation point, as the hair fails to grow and falls out. Sometimes, patches of alopecia may coalesce into a larger area. Nail changes may be noted, as well. Nails may become brittle, with pitting and/or longitudinal ridges. Patients are usually asymptomatic but may complain of pruritus.

AA is believed to be an autoimmune disorder. It affects males and females of all ages but is more common in children and young adults. AA is believed to result from a T-cell–mediated immune response that transitions the hair follicles from the growth phase to the resting phase. This leads to sudden hair loss and inhibition of regrowth of the hair. However, the hair follicle is not permanently destroyed as in other processes of alopecia. There is also an association between AA and other autoimmune disorders such as vitiligo, thyroid disease, and lupus.

The diagnosis usually is made clinically, as in this patient, but a definitive diagnosis can be made by biopsy and pathology. Other differential diagnoses to consider are trichotillomania, tinea, traumatic alopecia, and lupus.

In almost half of cases, AA is self-resolving; therefore, in first episodes of localized disease, watchful waiting is appropriate. Treatment is tailored to the individual patient and may be difficult. Intralesional corticosteroids often are used for mild cases. Typically, 10 mg/mL of a glucocorticoid is injected into the mid-dermis every 4 to 6 weeks; however, this treatment carries a risk of transient or even permanent atrophy of the injection site. Potent topical corticosteroids often are used, especially in children who do not tolerate intralesional injections, and success can be variable. Other topical treatments to consider are photochemotherapy (psoralen plus UVA), or an irritant agent such as anthralin and a vasodilator such as minoxidil. Regrowth can be expected in a few months to a year, but recurrence is common.

‌

Image courtesy of Stacy Nguy, MD, and text courtesy of Stacy Nguy, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

COVID-19–positive patients undergoing an invasive strategy for acute coronary syndrome presented hours later than uninfected historical controls, had a far higher incidence of cardiogenic shock, and their in-hospital mortality rate was four- to fivefold greater, according to data from the Global Multicenter Prospective COVID–ACS Registry. These phenomena are probably interrelated, according to Anthony Gershlick, MBBS, who presented the registry results at the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

“We know that increasing ischemic time leads to bigger infarcts. And we know that bigger infarcts lead to cardiogenic shock, with its known higher mortality,” said Dr. Gershlick, professor of interventional cardiology at the University of Leicester (England).

“These data suggest that patients may have presented late, likely due to COVID concerns, and they had worse outcomes. If these data are borne out, future public information strategies need to be reassuring, proactive, simple, and more effective because we think patients stayed away,” the cardiologist added. “There are important public information messages to be taken from these data about getting patients to come to hospital during such pandemics.”

He presented prospectively collected registry data on 144 patients with confirmed ST-elevation MI (STEMI) and 122 with non-ST–elevation MI (NSTEMI), all COVID-19 positive on presentation at 85 hospitals in the United Kingdom, Europe, and North America during March through August of 2020. Since the initial message to the public early in the pandemic in many places was to try to avoid the hospital, the investigators selected for their no-COVID comparison group the data on more than 22,000 STEMI and NSTEMI patients included in two British national databases covering 2018-2019.

The COVID-positive STEMI patients were significantly younger, had more comorbidities, and had a higher mean heart rate and lower systolic blood pressure at admission than the non-COVID STEMI control group. Their median time from symptom onset to admission was 339 minutes, compared with 178 minutes in controls. Their door-to-balloon time averaged 83 minutes, versus 37 minutes in the era before the pandemic.

“I suspect that’s got something to do with the donning and doffing of personal protective equipment,” he said at the meeting sponsored by the Cardiovascular Research Foundation.

The in-hospital mortality rates were strikingly different: 27.1% in COVID-positive STEMI patients versus 5.7% in controls. Bleeding Academic Research Consortium type 3-5 bleeding was increased as well, by a margin of 2.8% to 0.3%. So was stroke, with a 2.1% in-hospital incidence in COVID-positive STEMI patients and a 0.1% rate in the comparator arm.

“But the biggest headline here for me was that the cardiogenic shock rate was 20.1% in the COVID-positive patients versus 8.7% in the non-COVID STEMI patients,” the cardiologist continued.

The same pattern held true among the COVID-positive NSTEMI patients: They were younger, sicker, and slower to present to the hospital than the non-COVID group. The in-hospital mortality rate was 6.6% in the COVID-positive NSTEMI patients, compared with 1.2% in the reference group. The COVID-positive patients had a 2.5% bleeding rate versus 0.1% in the controls. And the incidence of cardiogenic shock was 5%, compared with 1.4% in the controls from before the pandemic.

“Even though NSTEMI is traditionally regarded as lower risk, this is really quite dramatic. These are sick patients,” Dr. Gershlick observed.

Nearly two-thirds of in-hospital deaths in COVID-positive ACS patients were cardiovascular, and three-quarters of those cardiovascular deaths occurred in patients with cardiogenic shock. Thirty-two percent of deaths in COVID-positive ACS patients were of respiratory causes, and 4.9% were neurologic.

Notably, the ischemic time of patients with cardiogenic shock who died – that is, the time from symptom onset to balloon deployment – averaged 1,271 minutes, compared with 441 minutes in those who died without being in cardiogenic shock.

Session comoderator Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center in New York, commented, “One of the striking things that is resonating with me is the high incidence of cardiogenic shock and the mortality. It’s akin to what we’ve seen in New York.”

[email protected]

COVID-19–positive patients undergoing an invasive strategy for acute coronary syndrome presented hours later than uninfected historical controls, had a far higher incidence of cardiogenic shock, and their in-hospital mortality rate was four- to fivefold greater, according to data from the Global Multicenter Prospective COVID–ACS Registry. These phenomena are probably interrelated, according to Anthony Gershlick, MBBS, who presented the registry results at the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

“We know that increasing ischemic time leads to bigger infarcts. And we know that bigger infarcts lead to cardiogenic shock, with its known higher mortality,” said Dr. Gershlick, professor of interventional cardiology at the University of Leicester (England).

“These data suggest that patients may have presented late, likely due to COVID concerns, and they had worse outcomes. If these data are borne out, future public information strategies need to be reassuring, proactive, simple, and more effective because we think patients stayed away,” the cardiologist added. “There are important public information messages to be taken from these data about getting patients to come to hospital during such pandemics.”

He presented prospectively collected registry data on 144 patients with confirmed ST-elevation MI (STEMI) and 122 with non-ST–elevation MI (NSTEMI), all COVID-19 positive on presentation at 85 hospitals in the United Kingdom, Europe, and North America during March through August of 2020. Since the initial message to the public early in the pandemic in many places was to try to avoid the hospital, the investigators selected for their no-COVID comparison group the data on more than 22,000 STEMI and NSTEMI patients included in two British national databases covering 2018-2019.

The COVID-positive STEMI patients were significantly younger, had more comorbidities, and had a higher mean heart rate and lower systolic blood pressure at admission than the non-COVID STEMI control group. Their median time from symptom onset to admission was 339 minutes, compared with 178 minutes in controls. Their door-to-balloon time averaged 83 minutes, versus 37 minutes in the era before the pandemic.

“I suspect that’s got something to do with the donning and doffing of personal protective equipment,” he said at the meeting sponsored by the Cardiovascular Research Foundation.

The in-hospital mortality rates were strikingly different: 27.1% in COVID-positive STEMI patients versus 5.7% in controls. Bleeding Academic Research Consortium type 3-5 bleeding was increased as well, by a margin of 2.8% to 0.3%. So was stroke, with a 2.1% in-hospital incidence in COVID-positive STEMI patients and a 0.1% rate in the comparator arm.

“But the biggest headline here for me was that the cardiogenic shock rate was 20.1% in the COVID-positive patients versus 8.7% in the non-COVID STEMI patients,” the cardiologist continued.

The same pattern held true among the COVID-positive NSTEMI patients: They were younger, sicker, and slower to present to the hospital than the non-COVID group. The in-hospital mortality rate was 6.6% in the COVID-positive NSTEMI patients, compared with 1.2% in the reference group. The COVID-positive patients had a 2.5% bleeding rate versus 0.1% in the controls. And the incidence of cardiogenic shock was 5%, compared with 1.4% in the controls from before the pandemic.

“Even though NSTEMI is traditionally regarded as lower risk, this is really quite dramatic. These are sick patients,” Dr. Gershlick observed.

Nearly two-thirds of in-hospital deaths in COVID-positive ACS patients were cardiovascular, and three-quarters of those cardiovascular deaths occurred in patients with cardiogenic shock. Thirty-two percent of deaths in COVID-positive ACS patients were of respiratory causes, and 4.9% were neurologic.

Notably, the ischemic time of patients with cardiogenic shock who died – that is, the time from symptom onset to balloon deployment – averaged 1,271 minutes, compared with 441 minutes in those who died without being in cardiogenic shock.

Session comoderator Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center in New York, commented, “One of the striking things that is resonating with me is the high incidence of cardiogenic shock and the mortality. It’s akin to what we’ve seen in New York.”

[email protected]

COVID-19–positive patients undergoing an invasive strategy for acute coronary syndrome presented hours later than uninfected historical controls, had a far higher incidence of cardiogenic shock, and their in-hospital mortality rate was four- to fivefold greater, according to data from the Global Multicenter Prospective COVID–ACS Registry. These phenomena are probably interrelated, according to Anthony Gershlick, MBBS, who presented the registry results at the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

“We know that increasing ischemic time leads to bigger infarcts. And we know that bigger infarcts lead to cardiogenic shock, with its known higher mortality,” said Dr. Gershlick, professor of interventional cardiology at the University of Leicester (England).

“These data suggest that patients may have presented late, likely due to COVID concerns, and they had worse outcomes. If these data are borne out, future public information strategies need to be reassuring, proactive, simple, and more effective because we think patients stayed away,” the cardiologist added. “There are important public information messages to be taken from these data about getting patients to come to hospital during such pandemics.”

He presented prospectively collected registry data on 144 patients with confirmed ST-elevation MI (STEMI) and 122 with non-ST–elevation MI (NSTEMI), all COVID-19 positive on presentation at 85 hospitals in the United Kingdom, Europe, and North America during March through August of 2020. Since the initial message to the public early in the pandemic in many places was to try to avoid the hospital, the investigators selected for their no-COVID comparison group the data on more than 22,000 STEMI and NSTEMI patients included in two British national databases covering 2018-2019.

The COVID-positive STEMI patients were significantly younger, had more comorbidities, and had a higher mean heart rate and lower systolic blood pressure at admission than the non-COVID STEMI control group. Their median time from symptom onset to admission was 339 minutes, compared with 178 minutes in controls. Their door-to-balloon time averaged 83 minutes, versus 37 minutes in the era before the pandemic.

“I suspect that’s got something to do with the donning and doffing of personal protective equipment,” he said at the meeting sponsored by the Cardiovascular Research Foundation.

The in-hospital mortality rates were strikingly different: 27.1% in COVID-positive STEMI patients versus 5.7% in controls. Bleeding Academic Research Consortium type 3-5 bleeding was increased as well, by a margin of 2.8% to 0.3%. So was stroke, with a 2.1% in-hospital incidence in COVID-positive STEMI patients and a 0.1% rate in the comparator arm.

“But the biggest headline here for me was that the cardiogenic shock rate was 20.1% in the COVID-positive patients versus 8.7% in the non-COVID STEMI patients,” the cardiologist continued.

The same pattern held true among the COVID-positive NSTEMI patients: They were younger, sicker, and slower to present to the hospital than the non-COVID group. The in-hospital mortality rate was 6.6% in the COVID-positive NSTEMI patients, compared with 1.2% in the reference group. The COVID-positive patients had a 2.5% bleeding rate versus 0.1% in the controls. And the incidence of cardiogenic shock was 5%, compared with 1.4% in the controls from before the pandemic.

“Even though NSTEMI is traditionally regarded as lower risk, this is really quite dramatic. These are sick patients,” Dr. Gershlick observed.

Nearly two-thirds of in-hospital deaths in COVID-positive ACS patients were cardiovascular, and three-quarters of those cardiovascular deaths occurred in patients with cardiogenic shock. Thirty-two percent of deaths in COVID-positive ACS patients were of respiratory causes, and 4.9% were neurologic.

Notably, the ischemic time of patients with cardiogenic shock who died – that is, the time from symptom onset to balloon deployment – averaged 1,271 minutes, compared with 441 minutes in those who died without being in cardiogenic shock.

Session comoderator Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center in New York, commented, “One of the striking things that is resonating with me is the high incidence of cardiogenic shock and the mortality. It’s akin to what we’ve seen in New York.”

[email protected]

The recent death of “Black Panther” star Chadwick Boseman has resulted in colorectal cancer (CRC) screening guidelines receiving more attention. Mr. Boseman was diagnosed with Stage 3 CRC in 2016 and underwent treatment. He passed away 4 years later at the young age of 44.

Mr. Boseman’s death has highlighted two important concerns about current screening guidelines for CRC. These include racial disparities in patients with colon cancer and the fact that more younger patients are getting this disease.

There are at least three different sets of CRC screening recommendations from different trusted professional organizations that primary care physicians must decide how to follow. These organizations each published their guidelines indicating review of the best available evidence. On first glance there is discrepancy between these guidelines, but a closer look at them reveals they have a lot of similarities.

The U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gatroenterological Association, and the American Society for Gastrointestinal Endoscopy, is one of the organizations that offers guidelines. The MSTF recommends CRC screening for non-African American average risked persons at the age of 50 years (strong recommendation; moderate quality evidence). The first-tier options for this recommendation are to have a colonoscopy every 10 years or annual fecal immunochemial test. Additionally, the MSTF recommends beginning screening of African Americans at age 45 years (weak recommendation; very-low-quality evidence). This recommendation cites higher incidence rates, earlier mean age at onset, higher proportion of cancers before age 50 years and late-stage presentation. The MSTF indicates that the increased rate of CRC at an earlier age in African Americans is caused by a combination of biologic and societal factors, but do not point to what those are. This earlier screening is not backed by evidence that it in fact improves morbidity or mortality outcomes. The MSTF also address screening among high-risk individuals. Those with first degree relatives with CRC or advanced adenomas diagnosed before the age of 60 years should be screened beginning at age 40 years or 10 years younger than the age the relative was diagnosed, whichever comes first, according to the MSTF recommendations. These individuals should have a colonoscopy every 5 years, the MSTF says. Those with first degree relatives with CRC or advanced adenomas diagnosed at older than 60 years should have CRC beginning at 40 years, though with the same testing intervals as average-risk individuals.¹

The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP), however, endorse the guidelines set forth by the United States Preventive Services Task Force (USPSTF). These guidelines were published in 2016 in the JAMA and notably are currently under review. These guidelines recommend routine screening for those at average risk at the age of 50 years. In the publication of these guidelines, the increasing incidence of CRC in those under 50 was acknowledged. It is however stated that the modest benefit of earlier diagnosis made via screening is not better than the increased risk of increased lifetime colonoscopy.²

The publication specifically addresses the disparity among Black adults who have the highest incidence and mortality rates in comparison with other racial/ethnic groups. These guidelines specifically state that there are higher rates of colon cancer among black adults. They however clarify that they think it is because of decreased screening and treatment in this group. When compared with other groups and the screening and treatment is controlled for, there is no longer a difference. Lowering the age for starting screening, therefore, won’t help resolve the disparity because the higher cases in Black adults has resulted from not enough Black adults being screened at the recommended age of 50, according to the USPSTF recommendation statement. As such, rather than changing the age of screening for Black adults, this publication recommends efforts to ensure that screening, follow-up, and treatment are received.

The USPSTF specifically did not include adults with known disorders that have a genetic predisposition to CRC or those with a first degree relative with CRC. They instead refer to other professional organizations for these recommendations.²

The American Cancer Society (ACS) also had a separate guideline published in CA: A Cancer Journal for Clinicians. It provides a qualified recommendation that CRC screening begin at age 45 years for those with average risk. The guideline also includes a strong recommendation for CRC screening beginning at age 50 years. The qualified recommendation for the younger age group is based on the incidence of colorectal cancer being similar between those aged 45-49 and those aged 50-54 years. The ACS also hypothesized that screening at an earlier age will decrease the disparity among population groups with a higher burden. Importantly, this updated guideline prioritized incidence reduction rather than mortality reduction. The ACS also stressed the need for a multipronged approach to mitigate barriers to CRC screening at the individual, provider, organizational, and policy levels. Similar to the USPSTF, the ACS did not address the screening of those with known disorders that have a genetic predisposition to CRC or those with a first degree relative with CRC.³

In all of the publications discussing CRC screening guidelines, it is stressed that there is not sufficient uptake of any of these recommendations. Rather than conduct earlier screening, in my opinion, we should focus on programmatic ways to ensure that the existing screening recommendations are followed. This is a space in which we can help affect the disparity seen among population groups.

The most important screening test is the one that patients are willing to use. Primary care physicians can use any of these guidelines to have conversations with patients about risk and when to start screening. Although these guidelines may seem to be different from each other, each one includes strong recommendations with the same information.

Additional studies should be done to determine the benefits and harms of screening in patients with known risk factors such as obesity, cigarette smoking, diabetes, high consumption of alcohol, high consumption of red meat and processed food, inactivity, and low intake of dietary fiber, fruits, and vegetables. It is possible that the higher burden of disease among Black adults is related to societal factors leading to increased obesity and dietary habits that increase rates of CRC.

Primary care physicians would be better served by a tool that allows for risk stratification to help guide early screening for all patients. For certain patients, such a tool might result in them qualifying for screening that begins at a later age than the current guidelines recommend. Finally, primary care physicians must remember that these are just the guidelines for screening for CRC. They all specifically exclude patients experiencing any symptoms. As such, patients with unexplained bleeding, anemia, weight loss, and other symptoms should be evaluated fully, including being considered for colonoscopy to diagnose CRC. Primary care physicians should use these guidelines to screen their asymptomatic patients and should ensure that they provide evaluation of any of the symptoms of CRC.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is also program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on editorial advisory board of Family Practice News.

References

1. Rex DK et al. Gastrointest Endosc. 2017;86(1):18-33.

2. US Preventive Services Task Force. JAMA. 2016;315(23):2564-2575.

3. Wolf AMD et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

[email protected]

The recent death of “Black Panther” star Chadwick Boseman has resulted in colorectal cancer (CRC) screening guidelines receiving more attention. Mr. Boseman was diagnosed with Stage 3 CRC in 2016 and underwent treatment. He passed away 4 years later at the young age of 44.

Mr. Boseman’s death has highlighted two important concerns about current screening guidelines for CRC. These include racial disparities in patients with colon cancer and the fact that more younger patients are getting this disease.

There are at least three different sets of CRC screening recommendations from different trusted professional organizations that primary care physicians must decide how to follow. These organizations each published their guidelines indicating review of the best available evidence. On first glance there is discrepancy between these guidelines, but a closer look at them reveals they have a lot of similarities.

The U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gatroenterological Association, and the American Society for Gastrointestinal Endoscopy, is one of the organizations that offers guidelines. The MSTF recommends CRC screening for non-African American average risked persons at the age of 50 years (strong recommendation; moderate quality evidence). The first-tier options for this recommendation are to have a colonoscopy every 10 years or annual fecal immunochemial test. Additionally, the MSTF recommends beginning screening of African Americans at age 45 years (weak recommendation; very-low-quality evidence). This recommendation cites higher incidence rates, earlier mean age at onset, higher proportion of cancers before age 50 years and late-stage presentation. The MSTF indicates that the increased rate of CRC at an earlier age in African Americans is caused by a combination of biologic and societal factors, but do not point to what those are. This earlier screening is not backed by evidence that it in fact improves morbidity or mortality outcomes. The MSTF also address screening among high-risk individuals. Those with first degree relatives with CRC or advanced adenomas diagnosed before the age of 60 years should be screened beginning at age 40 years or 10 years younger than the age the relative was diagnosed, whichever comes first, according to the MSTF recommendations. These individuals should have a colonoscopy every 5 years, the MSTF says. Those with first degree relatives with CRC or advanced adenomas diagnosed at older than 60 years should have CRC beginning at 40 years, though with the same testing intervals as average-risk individuals.¹

The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP), however, endorse the guidelines set forth by the United States Preventive Services Task Force (USPSTF). These guidelines were published in 2016 in the JAMA and notably are currently under review. These guidelines recommend routine screening for those at average risk at the age of 50 years. In the publication of these guidelines, the increasing incidence of CRC in those under 50 was acknowledged. It is however stated that the modest benefit of earlier diagnosis made via screening is not better than the increased risk of increased lifetime colonoscopy.²

The publication specifically addresses the disparity among Black adults who have the highest incidence and mortality rates in comparison with other racial/ethnic groups. These guidelines specifically state that there are higher rates of colon cancer among black adults. They however clarify that they think it is because of decreased screening and treatment in this group. When compared with other groups and the screening and treatment is controlled for, there is no longer a difference. Lowering the age for starting screening, therefore, won’t help resolve the disparity because the higher cases in Black adults has resulted from not enough Black adults being screened at the recommended age of 50, according to the USPSTF recommendation statement. As such, rather than changing the age of screening for Black adults, this publication recommends efforts to ensure that screening, follow-up, and treatment are received.

The USPSTF specifically did not include adults with known disorders that have a genetic predisposition to CRC or those with a first degree relative with CRC. They instead refer to other professional organizations for these recommendations.²

The American Cancer Society (ACS) also had a separate guideline published in CA: A Cancer Journal for Clinicians. It provides a qualified recommendation that CRC screening begin at age 45 years for those with average risk. The guideline also includes a strong recommendation for CRC screening beginning at age 50 years. The qualified recommendation for the younger age group is based on the incidence of colorectal cancer being similar between those aged 45-49 and those aged 50-54 years. The ACS also hypothesized that screening at an earlier age will decrease the disparity among population groups with a higher burden. Importantly, this updated guideline prioritized incidence reduction rather than mortality reduction. The ACS also stressed the need for a multipronged approach to mitigate barriers to CRC screening at the individual, provider, organizational, and policy levels. Similar to the USPSTF, the ACS did not address the screening of those with known disorders that have a genetic predisposition to CRC or those with a first degree relative with CRC.³

In all of the publications discussing CRC screening guidelines, it is stressed that there is not sufficient uptake of any of these recommendations. Rather than conduct earlier screening, in my opinion, we should focus on programmatic ways to ensure that the existing screening recommendations are followed. This is a space in which we can help affect the disparity seen among population groups.

The most important screening test is the one that patients are willing to use. Primary care physicians can use any of these guidelines to have conversations with patients about risk and when to start screening. Although these guidelines may seem to be different from each other, each one includes strong recommendations with the same information.

Additional studies should be done to determine the benefits and harms of screening in patients with known risk factors such as obesity, cigarette smoking, diabetes, high consumption of alcohol, high consumption of red meat and processed food, inactivity, and low intake of dietary fiber, fruits, and vegetables. It is possible that the higher burden of disease among Black adults is related to societal factors leading to increased obesity and dietary habits that increase rates of CRC.

Primary care physicians would be better served by a tool that allows for risk stratification to help guide early screening for all patients. For certain patients, such a tool might result in them qualifying for screening that begins at a later age than the current guidelines recommend. Finally, primary care physicians must remember that these are just the guidelines for screening for CRC. They all specifically exclude patients experiencing any symptoms. As such, patients with unexplained bleeding, anemia, weight loss, and other symptoms should be evaluated fully, including being considered for colonoscopy to diagnose CRC. Primary care physicians should use these guidelines to screen their asymptomatic patients and should ensure that they provide evaluation of any of the symptoms of CRC.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is also program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on editorial advisory board of Family Practice News.

References

1. Rex DK et al. Gastrointest Endosc. 2017;86(1):18-33.

2. US Preventive Services Task Force. JAMA. 2016;315(23):2564-2575.

3. Wolf AMD et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

[email protected]

The recent death of “Black Panther” star Chadwick Boseman has resulted in colorectal cancer (CRC) screening guidelines receiving more attention. Mr. Boseman was diagnosed with Stage 3 CRC in 2016 and underwent treatment. He passed away 4 years later at the young age of 44.

Mr. Boseman’s death has highlighted two important concerns about current screening guidelines for CRC. These include racial disparities in patients with colon cancer and the fact that more younger patients are getting this disease.

There are at least three different sets of CRC screening recommendations from different trusted professional organizations that primary care physicians must decide how to follow. These organizations each published their guidelines indicating review of the best available evidence. On first glance there is discrepancy between these guidelines, but a closer look at them reveals they have a lot of similarities.

The U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gatroenterological Association, and the American Society for Gastrointestinal Endoscopy, is one of the organizations that offers guidelines. The MSTF recommends CRC screening for non-African American average risked persons at the age of 50 years (strong recommendation; moderate quality evidence). The first-tier options for this recommendation are to have a colonoscopy every 10 years or annual fecal immunochemial test. Additionally, the MSTF recommends beginning screening of African Americans at age 45 years (weak recommendation; very-low-quality evidence). This recommendation cites higher incidence rates, earlier mean age at onset, higher proportion of cancers before age 50 years and late-stage presentation. The MSTF indicates that the increased rate of CRC at an earlier age in African Americans is caused by a combination of biologic and societal factors, but do not point to what those are. This earlier screening is not backed by evidence that it in fact improves morbidity or mortality outcomes. The MSTF also address screening among high-risk individuals. Those with first degree relatives with CRC or advanced adenomas diagnosed before the age of 60 years should be screened beginning at age 40 years or 10 years younger than the age the relative was diagnosed, whichever comes first, according to the MSTF recommendations. These individuals should have a colonoscopy every 5 years, the MSTF says. Those with first degree relatives with CRC or advanced adenomas diagnosed at older than 60 years should have CRC beginning at 40 years, though with the same testing intervals as average-risk individuals.¹

The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP), however, endorse the guidelines set forth by the United States Preventive Services Task Force (USPSTF). These guidelines were published in 2016 in the JAMA and notably are currently under review. These guidelines recommend routine screening for those at average risk at the age of 50 years. In the publication of these guidelines, the increasing incidence of CRC in those under 50 was acknowledged. It is however stated that the modest benefit of earlier diagnosis made via screening is not better than the increased risk of increased lifetime colonoscopy.²

The publication specifically addresses the disparity among Black adults who have the highest incidence and mortality rates in comparison with other racial/ethnic groups. These guidelines specifically state that there are higher rates of colon cancer among black adults. They however clarify that they think it is because of decreased screening and treatment in this group. When compared with other groups and the screening and treatment is controlled for, there is no longer a difference. Lowering the age for starting screening, therefore, won’t help resolve the disparity because the higher cases in Black adults has resulted from not enough Black adults being screened at the recommended age of 50, according to the USPSTF recommendation statement. As such, rather than changing the age of screening for Black adults, this publication recommends efforts to ensure that screening, follow-up, and treatment are received.

The USPSTF specifically did not include adults with known disorders that have a genetic predisposition to CRC or those with a first degree relative with CRC. They instead refer to other professional organizations for these recommendations.²

The American Cancer Society (ACS) also had a separate guideline published in CA: A Cancer Journal for Clinicians. It provides a qualified recommendation that CRC screening begin at age 45 years for those with average risk. The guideline also includes a strong recommendation for CRC screening beginning at age 50 years. The qualified recommendation for the younger age group is based on the incidence of colorectal cancer being similar between those aged 45-49 and those aged 50-54 years. The ACS also hypothesized that screening at an earlier age will decrease the disparity among population groups with a higher burden. Importantly, this updated guideline prioritized incidence reduction rather than mortality reduction. The ACS also stressed the need for a multipronged approach to mitigate barriers to CRC screening at the individual, provider, organizational, and policy levels. Similar to the USPSTF, the ACS did not address the screening of those with known disorders that have a genetic predisposition to CRC or those with a first degree relative with CRC.³

In all of the publications discussing CRC screening guidelines, it is stressed that there is not sufficient uptake of any of these recommendations. Rather than conduct earlier screening, in my opinion, we should focus on programmatic ways to ensure that the existing screening recommendations are followed. This is a space in which we can help affect the disparity seen among population groups.

The most important screening test is the one that patients are willing to use. Primary care physicians can use any of these guidelines to have conversations with patients about risk and when to start screening. Although these guidelines may seem to be different from each other, each one includes strong recommendations with the same information.

Additional studies should be done to determine the benefits and harms of screening in patients with known risk factors such as obesity, cigarette smoking, diabetes, high consumption of alcohol, high consumption of red meat and processed food, inactivity, and low intake of dietary fiber, fruits, and vegetables. It is possible that the higher burden of disease among Black adults is related to societal factors leading to increased obesity and dietary habits that increase rates of CRC.

Primary care physicians would be better served by a tool that allows for risk stratification to help guide early screening for all patients. For certain patients, such a tool might result in them qualifying for screening that begins at a later age than the current guidelines recommend. Finally, primary care physicians must remember that these are just the guidelines for screening for CRC. They all specifically exclude patients experiencing any symptoms. As such, patients with unexplained bleeding, anemia, weight loss, and other symptoms should be evaluated fully, including being considered for colonoscopy to diagnose CRC. Primary care physicians should use these guidelines to screen their asymptomatic patients and should ensure that they provide evaluation of any of the symptoms of CRC.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is also program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on editorial advisory board of Family Practice News.

References

1. Rex DK et al. Gastrointest Endosc. 2017;86(1):18-33.

2. US Preventive Services Task Force. JAMA. 2016;315(23):2564-2575.

3. Wolf AMD et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

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Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.