An updated worldwide estimate of complementary and alternative medicine (CAM) use among individuals with diabetes found widespread use, though it varied greatly by region and is sometimes hard to define.

The report is the first literature review of the subject since 2007. The researchers looked at CAM use by region, as well as by patient categories such as those with advanced diabetes and by length of time since diagnosis. The most commonly reported CAMs in use were herbal medicine, acupuncture, homeopathy, and spiritual healing.

Only about one-third of patients disclosed their CAM use to their physician or health care provider. “We suggest that health care professionals should carefully anticipate the likelihood of their [patients’] diabetic CAM use in order to enhance treatment optimization and promote medication adherence, as well as to provide a fully informed consultation,” said first author Abdulaziz S. Alzahrani, a PhD student at the University of Birmingham (England). The study was published March 8, 2021, in the European Journal of Clinical Pharmacology.

Patients also have a responsibility, said Gregory Rhee, PhD, assistant professor of public health sciences at the University of Connecticut, Farmington. He was the lead author of a 2018 survey of CAM use in adults aged 65 years and older with diabetes in the United States using data from the 2012 National Health Interview Survey, and found that 25% had used CAM in some form in the prior year. “They need to be more up front, more proactive talking about CAM use with their doctors, and the second part is the physician. They also should be better educated in terms of CAM use. Traditionally, the physician in Western societies have pretty much ignored CAM use. But they are getting aware of CAM use and also we know that people are coming from multiple cultural backgrounds. The physicians and other health care providers should be better informed about CAM, and they should be better educated about it to provide patients better practice,” said Dr. Rhee.

He also distinguished between approaches like yoga or Tai Chi, which are physically oriented and not particularly controversial, and herbal medicines or dietary supplements. “Those can be controversial because we do not have strong scientific evidence to support those modalities for effectiveness on diabetes management,” Dr. Rhee added.

Mr. Alzahrani and colleagues conducted a meta-analysis of 38 studies, which included data from 25 countries. The included studies varied in their approach. For example, 16 studies focused exclusively on herbal and nutritional supplements. The most commonly mentioned CAMs were acupuncture and mind-body therapies (each named in six studies), religious and spiritual healing (five studies), and homeopathy (four studies). Among 31 studies focusing on herbal and nutritional supplements, the most common herbs mentioned were cinnamon and fenugreek (mentioned in 18 studies), garlic (17 studies), aloe vera (14 studies), and black seed (12 studies).

Prevalence of CAM use varied widely, ranging from 17% in Jordan to 89% in India and in a separate study in Jordan. The pooled prevalence of CAM use was 51% (95% confidence interval, 43%-59%). Subgroup analyses found the highest rate of CAM use in Europe (76%) and Africa (55%), and the lowest in North America (45%).

When the researchers examined patient characteristics, they found no significant relationship between CAM use and established ethnicity groups, or between type 1 and type 2 diabetes. The prevalence ratio was lower among men (PR, 0.86; 95% CI, 0.81-0.91). PRs for CAM use were lower among those with diabetic complications (PR, 0.81; 95% CI, 0.66-0.99). Individuals with diabetes of at least 5 years’ duration were more likely to use CAM than those with shorter duration of illness (PR, 1.71; 95% CI, 1.04-1.32).

Most (78%) CAM users employed it as an addition to their treatment regimen (95% CI, 56-94%), while 21% used it as an alternative to prescribed medicine (95% CI, 12-31%). More than two-thirds (67%) of individuals did not disclose CAM use to health care professionals (95% CI, 58-76%).

Although CAM use can be a source of friction between patients and physicians, Dr. Rhee also sees it as an opportunity. Patients from diverse backgrounds may be using CAM, often as a result of different cultural backgrounds. He cited the belief in some Asian countries that the balance of Yin and Yang is key to health, which many patients believe can be addressed through CAM. “If we want to promote cultural diversity, if we really care about patient diversity, I think CAM is one of the potential sources where the doctors should know [more about] the issue,” said Dr. Rhee.

The study was funded by the University of Birmingham. Dr. Rhee and Mr. Alzahrani have no relevant financial disclosures.

An updated worldwide estimate of complementary and alternative medicine (CAM) use among individuals with diabetes found widespread use, though it varied greatly by region and is sometimes hard to define.

The report is the first literature review of the subject since 2007. The researchers looked at CAM use by region, as well as by patient categories such as those with advanced diabetes and by length of time since diagnosis. The most commonly reported CAMs in use were herbal medicine, acupuncture, homeopathy, and spiritual healing.

Only about one-third of patients disclosed their CAM use to their physician or health care provider. “We suggest that health care professionals should carefully anticipate the likelihood of their [patients’] diabetic CAM use in order to enhance treatment optimization and promote medication adherence, as well as to provide a fully informed consultation,” said first author Abdulaziz S. Alzahrani, a PhD student at the University of Birmingham (England). The study was published March 8, 2021, in the European Journal of Clinical Pharmacology.

Patients also have a responsibility, said Gregory Rhee, PhD, assistant professor of public health sciences at the University of Connecticut, Farmington. He was the lead author of a 2018 survey of CAM use in adults aged 65 years and older with diabetes in the United States using data from the 2012 National Health Interview Survey, and found that 25% had used CAM in some form in the prior year. “They need to be more up front, more proactive talking about CAM use with their doctors, and the second part is the physician. They also should be better educated in terms of CAM use. Traditionally, the physician in Western societies have pretty much ignored CAM use. But they are getting aware of CAM use and also we know that people are coming from multiple cultural backgrounds. The physicians and other health care providers should be better informed about CAM, and they should be better educated about it to provide patients better practice,” said Dr. Rhee.

He also distinguished between approaches like yoga or Tai Chi, which are physically oriented and not particularly controversial, and herbal medicines or dietary supplements. “Those can be controversial because we do not have strong scientific evidence to support those modalities for effectiveness on diabetes management,” Dr. Rhee added.

Mr. Alzahrani and colleagues conducted a meta-analysis of 38 studies, which included data from 25 countries. The included studies varied in their approach. For example, 16 studies focused exclusively on herbal and nutritional supplements. The most commonly mentioned CAMs were acupuncture and mind-body therapies (each named in six studies), religious and spiritual healing (five studies), and homeopathy (four studies). Among 31 studies focusing on herbal and nutritional supplements, the most common herbs mentioned were cinnamon and fenugreek (mentioned in 18 studies), garlic (17 studies), aloe vera (14 studies), and black seed (12 studies).

Prevalence of CAM use varied widely, ranging from 17% in Jordan to 89% in India and in a separate study in Jordan. The pooled prevalence of CAM use was 51% (95% confidence interval, 43%-59%). Subgroup analyses found the highest rate of CAM use in Europe (76%) and Africa (55%), and the lowest in North America (45%).

When the researchers examined patient characteristics, they found no significant relationship between CAM use and established ethnicity groups, or between type 1 and type 2 diabetes. The prevalence ratio was lower among men (PR, 0.86; 95% CI, 0.81-0.91). PRs for CAM use were lower among those with diabetic complications (PR, 0.81; 95% CI, 0.66-0.99). Individuals with diabetes of at least 5 years’ duration were more likely to use CAM than those with shorter duration of illness (PR, 1.71; 95% CI, 1.04-1.32).

Most (78%) CAM users employed it as an addition to their treatment regimen (95% CI, 56-94%), while 21% used it as an alternative to prescribed medicine (95% CI, 12-31%). More than two-thirds (67%) of individuals did not disclose CAM use to health care professionals (95% CI, 58-76%).

Although CAM use can be a source of friction between patients and physicians, Dr. Rhee also sees it as an opportunity. Patients from diverse backgrounds may be using CAM, often as a result of different cultural backgrounds. He cited the belief in some Asian countries that the balance of Yin and Yang is key to health, which many patients believe can be addressed through CAM. “If we want to promote cultural diversity, if we really care about patient diversity, I think CAM is one of the potential sources where the doctors should know [more about] the issue,” said Dr. Rhee.

The study was funded by the University of Birmingham. Dr. Rhee and Mr. Alzahrani have no relevant financial disclosures.

An updated worldwide estimate of complementary and alternative medicine (CAM) use among individuals with diabetes found widespread use, though it varied greatly by region and is sometimes hard to define.

The report is the first literature review of the subject since 2007. The researchers looked at CAM use by region, as well as by patient categories such as those with advanced diabetes and by length of time since diagnosis. The most commonly reported CAMs in use were herbal medicine, acupuncture, homeopathy, and spiritual healing.

Only about one-third of patients disclosed their CAM use to their physician or health care provider. “We suggest that health care professionals should carefully anticipate the likelihood of their [patients’] diabetic CAM use in order to enhance treatment optimization and promote medication adherence, as well as to provide a fully informed consultation,” said first author Abdulaziz S. Alzahrani, a PhD student at the University of Birmingham (England). The study was published March 8, 2021, in the European Journal of Clinical Pharmacology.

Patients also have a responsibility, said Gregory Rhee, PhD, assistant professor of public health sciences at the University of Connecticut, Farmington. He was the lead author of a 2018 survey of CAM use in adults aged 65 years and older with diabetes in the United States using data from the 2012 National Health Interview Survey, and found that 25% had used CAM in some form in the prior year. “They need to be more up front, more proactive talking about CAM use with their doctors, and the second part is the physician. They also should be better educated in terms of CAM use. Traditionally, the physician in Western societies have pretty much ignored CAM use. But they are getting aware of CAM use and also we know that people are coming from multiple cultural backgrounds. The physicians and other health care providers should be better informed about CAM, and they should be better educated about it to provide patients better practice,” said Dr. Rhee.

He also distinguished between approaches like yoga or Tai Chi, which are physically oriented and not particularly controversial, and herbal medicines or dietary supplements. “Those can be controversial because we do not have strong scientific evidence to support those modalities for effectiveness on diabetes management,” Dr. Rhee added.

Mr. Alzahrani and colleagues conducted a meta-analysis of 38 studies, which included data from 25 countries. The included studies varied in their approach. For example, 16 studies focused exclusively on herbal and nutritional supplements. The most commonly mentioned CAMs were acupuncture and mind-body therapies (each named in six studies), religious and spiritual healing (five studies), and homeopathy (four studies). Among 31 studies focusing on herbal and nutritional supplements, the most common herbs mentioned were cinnamon and fenugreek (mentioned in 18 studies), garlic (17 studies), aloe vera (14 studies), and black seed (12 studies).

Prevalence of CAM use varied widely, ranging from 17% in Jordan to 89% in India and in a separate study in Jordan. The pooled prevalence of CAM use was 51% (95% confidence interval, 43%-59%). Subgroup analyses found the highest rate of CAM use in Europe (76%) and Africa (55%), and the lowest in North America (45%).

When the researchers examined patient characteristics, they found no significant relationship between CAM use and established ethnicity groups, or between type 1 and type 2 diabetes. The prevalence ratio was lower among men (PR, 0.86; 95% CI, 0.81-0.91). PRs for CAM use were lower among those with diabetic complications (PR, 0.81; 95% CI, 0.66-0.99). Individuals with diabetes of at least 5 years’ duration were more likely to use CAM than those with shorter duration of illness (PR, 1.71; 95% CI, 1.04-1.32).

Most (78%) CAM users employed it as an addition to their treatment regimen (95% CI, 56-94%), while 21% used it as an alternative to prescribed medicine (95% CI, 12-31%). More than two-thirds (67%) of individuals did not disclose CAM use to health care professionals (95% CI, 58-76%).

Although CAM use can be a source of friction between patients and physicians, Dr. Rhee also sees it as an opportunity. Patients from diverse backgrounds may be using CAM, often as a result of different cultural backgrounds. He cited the belief in some Asian countries that the balance of Yin and Yang is key to health, which many patients believe can be addressed through CAM. “If we want to promote cultural diversity, if we really care about patient diversity, I think CAM is one of the potential sources where the doctors should know [more about] the issue,” said Dr. Rhee.

The study was funded by the University of Birmingham. Dr. Rhee and Mr. Alzahrani have no relevant financial disclosures.

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Obesity rates among children jumped substantially in the first months of the COVID-19 pandemic, according to a study published online in Pediatrics. Experts worry the excess weight will be a continuing problem for these children.

“Across the board in the span of a year, there has been a 2% increase in obesity, which is really striking,” lead author Brian P. Jenssen, MD, said in an interview.

The prevalence of obesity in a large pediatric primary care network increased from 13.7% to 15.4%.

Preexisting disparities by race or ethnicity and socioeconomic status worsened, noted Dr. Jenssen, a primary care pediatrician affiliated with Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania, Philadelphia.

Dr. Jenssen and colleagues compared the average obesity rate from June to December 2020 with the rate from June to December 2019 among patients in the CHOP Care Network, which includes 29 urban, suburban, and semirural clinics in the Philadelphia region. In June 2020, the volume of patient visits “returned to near-normal” after a dramatic decline in March 2020, the study authors wrote.

The investigators examined body mass index at all visits for patients aged 2-17 years for whom height and weight were documented. Patients with a BMI at or above the 95th percentile were classified as obese. The analysis included approximately 169,000 visits in 2019 and about 145,000 in 2020.

The average age of the patients was 9.2 years, and 48.9% were girls. In all, 21.4% were non-Hispanic Black, and about 30% were publicly insured.

Increases in obesity rates were more pronounced among patients aged 5-9 years and among patients who were Hispanic/Latino, non-Hispanic Black, publicly insured, or from lower-income neighborhoods.

Whereas the obesity rate increased 1% for patients aged 13-17 years, the rate increased 2.6% for patients aged 5-9 years.

Nearly 25% of Hispanic/Latino or non-Hispanic Black patients seen during the pandemic were obese, compared with 11.3% of non-Hispanic White patients. Before the pandemic, differences by race or ethnicity had been about 10%-11%.

Limiting the analysis to preventive visits did not meaningfully change the results, wrote Dr. Jenssen and colleagues.

“Having any increase in the obesity rates is alarming,” said Sandra Hassink, MD, medical director for the American Academy of Pediatrics’ (AAP’s) Institute for Healthy Childhood Weight. “I think what we’re seeing is what we feared.”

Before the pandemic, children received appropriately portioned breakfasts and lunches at school, but during the pandemic, they had less access to such meals, the academy noted. Disruptions to schooling, easier access to unhealthy snacks, increased screen time, and economic issues such as parents’ job losses were further factors, Hassink said.
 

Tackling the weight gain

In December 2020, the AAP issued two clinical guidance documents to highlight the importance of addressing obesity during the pandemic. Recommendations included physician counseling of families about maintaining healthy nutrition, minimizing sedentary time, and getting enough sleep and physical activity, as well as the assessment of all patients for onset of obesity and the maintenance of obesity treatment for patients with obesity.

In addition to clinical assessments and guidance, Dr. Jenssen emphasized that a return to routines may be crucial. Prepandemic studies have shown that many children, especially those insured by Medicaid, gain more weight during the summer when they are out of school, he noted. Many of the same factors are present during the pandemic, he said.

“One solution, and probably the most important solution, is getting kids back in school,” Dr. Jenssen said. School disruptions also have affected children’s learning and mental health, but those effects may be harder to quantify than BMI, he said.

Dr. Jenssen suggests that parents do their best to model good routines and habits. For example, they might decide that they and their children will stop drinking soda as a family, or opt for an apple instead of a bag of chips. They can walk around the house or up and down stairs when talking. “Those sorts of little things can make a big difference in the long run,” Dr. Jenssen said.

Clinicians should address obesity in a compassionate and caring way, be aware of community resources to help families adopt healthy lifestyles, and “look for the comorbidities of obesity,” such as type 2 diabetes, liver disease, sleep apnea, knee problems, and hypertension, Dr. Hassink said.

Policies that address other factors, such as the cost of healthy foods and the marketing of unhealthy foods, may also be needed, Dr. Hassink said.

“I’ve always thought of obesity as kind of the canary in the coal mine,” Dr. Hassink said. “It is important to keep our minds on the fact that it is a chronic disease. But it also indicates a lot of things about how we are able to support a healthy population.”
 

Potato chips, red meat, and sugary drinks

Other researchers have assessed how healthy behaviors tended to take a turn for the worse when routines were disrupted during the pandemic. Steven B. Heymsfield, MD, a professor in the metabolism and body composition laboratory at Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and collaborators documented how diet and activity changed for children during the pandemic.

Dr. Heymsfield worked with researchers in Italy to examine changes in behavior among 41 children and adolescents with obesity in Verona, Italy, during an early lockdown.

As part of a longitudinal observational study, they had baseline data about diet and physical activity from interviews conducted from May to July 2019. They repeated the interviews 3 weeks after a mandatory quarantine.

Intake of potato chips, red meat, and sugary drinks had increased, time spent in sports activities had decreased by more than 2 hours per week, and screen time had increased by more than 4 hours per day, the researchers found. Their study was published in Obesity.

Unpublished follow-up data indicate that “there was further deterioration in the diets and activity patterns” for some but not all of the participants, Dr. Heymsfield said.

He said he was hopeful that children who experienced the onset of obesity during the pandemic may lose weight when routines return to normal, but added that it is unclear whether that will happen.

“My impression from the limited written literature on this question is that for some kids who gain weight during the lockdown or, by analogy, the summer months, the weight doesn’t go back down again. It is not universal, but it is a known phenomenon that it is a bit of a ratchet,” he said. “They just sort of slowly ratchet their weights up, up to adulthood.”

Recognizing weight gain during the pandemic may be an important first step.

“The first thing is not to ignore it,” Dr. Heymsfield said. “Anything that can be done to prevent excess weight gain during childhood – not to promote anorexia or anything like that, but just being careful – is very important, because these behaviors are formed early in life, and they persist.”

CHOP supported the research. Dr. Jenssen and Dr. Hassink have disclosed no relevant financial relationships. Dr. Heymsfield is a medical adviser for Medifast, a weight loss company.

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

Obesity rates among children jumped substantially in the first months of the COVID-19 pandemic, according to a study published online in Pediatrics. Experts worry the excess weight will be a continuing problem for these children.

“Across the board in the span of a year, there has been a 2% increase in obesity, which is really striking,” lead author Brian P. Jenssen, MD, said in an interview.

The prevalence of obesity in a large pediatric primary care network increased from 13.7% to 15.4%.

Preexisting disparities by race or ethnicity and socioeconomic status worsened, noted Dr. Jenssen, a primary care pediatrician affiliated with Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania, Philadelphia.

Dr. Jenssen and colleagues compared the average obesity rate from June to December 2020 with the rate from June to December 2019 among patients in the CHOP Care Network, which includes 29 urban, suburban, and semirural clinics in the Philadelphia region. In June 2020, the volume of patient visits “returned to near-normal” after a dramatic decline in March 2020, the study authors wrote.

The investigators examined body mass index at all visits for patients aged 2-17 years for whom height and weight were documented. Patients with a BMI at or above the 95th percentile were classified as obese. The analysis included approximately 169,000 visits in 2019 and about 145,000 in 2020.

The average age of the patients was 9.2 years, and 48.9% were girls. In all, 21.4% were non-Hispanic Black, and about 30% were publicly insured.

Increases in obesity rates were more pronounced among patients aged 5-9 years and among patients who were Hispanic/Latino, non-Hispanic Black, publicly insured, or from lower-income neighborhoods.

Whereas the obesity rate increased 1% for patients aged 13-17 years, the rate increased 2.6% for patients aged 5-9 years.

Nearly 25% of Hispanic/Latino or non-Hispanic Black patients seen during the pandemic were obese, compared with 11.3% of non-Hispanic White patients. Before the pandemic, differences by race or ethnicity had been about 10%-11%.

Limiting the analysis to preventive visits did not meaningfully change the results, wrote Dr. Jenssen and colleagues.

“Having any increase in the obesity rates is alarming,” said Sandra Hassink, MD, medical director for the American Academy of Pediatrics’ (AAP’s) Institute for Healthy Childhood Weight. “I think what we’re seeing is what we feared.”

Before the pandemic, children received appropriately portioned breakfasts and lunches at school, but during the pandemic, they had less access to such meals, the academy noted. Disruptions to schooling, easier access to unhealthy snacks, increased screen time, and economic issues such as parents’ job losses were further factors, Hassink said.
 

Tackling the weight gain

In December 2020, the AAP issued two clinical guidance documents to highlight the importance of addressing obesity during the pandemic. Recommendations included physician counseling of families about maintaining healthy nutrition, minimizing sedentary time, and getting enough sleep and physical activity, as well as the assessment of all patients for onset of obesity and the maintenance of obesity treatment for patients with obesity.

In addition to clinical assessments and guidance, Dr. Jenssen emphasized that a return to routines may be crucial. Prepandemic studies have shown that many children, especially those insured by Medicaid, gain more weight during the summer when they are out of school, he noted. Many of the same factors are present during the pandemic, he said.

“One solution, and probably the most important solution, is getting kids back in school,” Dr. Jenssen said. School disruptions also have affected children’s learning and mental health, but those effects may be harder to quantify than BMI, he said.

Dr. Jenssen suggests that parents do their best to model good routines and habits. For example, they might decide that they and their children will stop drinking soda as a family, or opt for an apple instead of a bag of chips. They can walk around the house or up and down stairs when talking. “Those sorts of little things can make a big difference in the long run,” Dr. Jenssen said.

Clinicians should address obesity in a compassionate and caring way, be aware of community resources to help families adopt healthy lifestyles, and “look for the comorbidities of obesity,” such as type 2 diabetes, liver disease, sleep apnea, knee problems, and hypertension, Dr. Hassink said.

Policies that address other factors, such as the cost of healthy foods and the marketing of unhealthy foods, may also be needed, Dr. Hassink said.

“I’ve always thought of obesity as kind of the canary in the coal mine,” Dr. Hassink said. “It is important to keep our minds on the fact that it is a chronic disease. But it also indicates a lot of things about how we are able to support a healthy population.”
 

Potato chips, red meat, and sugary drinks

Other researchers have assessed how healthy behaviors tended to take a turn for the worse when routines were disrupted during the pandemic. Steven B. Heymsfield, MD, a professor in the metabolism and body composition laboratory at Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and collaborators documented how diet and activity changed for children during the pandemic.

Dr. Heymsfield worked with researchers in Italy to examine changes in behavior among 41 children and adolescents with obesity in Verona, Italy, during an early lockdown.

As part of a longitudinal observational study, they had baseline data about diet and physical activity from interviews conducted from May to July 2019. They repeated the interviews 3 weeks after a mandatory quarantine.

Intake of potato chips, red meat, and sugary drinks had increased, time spent in sports activities had decreased by more than 2 hours per week, and screen time had increased by more than 4 hours per day, the researchers found. Their study was published in Obesity.

Unpublished follow-up data indicate that “there was further deterioration in the diets and activity patterns” for some but not all of the participants, Dr. Heymsfield said.

He said he was hopeful that children who experienced the onset of obesity during the pandemic may lose weight when routines return to normal, but added that it is unclear whether that will happen.

“My impression from the limited written literature on this question is that for some kids who gain weight during the lockdown or, by analogy, the summer months, the weight doesn’t go back down again. It is not universal, but it is a known phenomenon that it is a bit of a ratchet,” he said. “They just sort of slowly ratchet their weights up, up to adulthood.”

Recognizing weight gain during the pandemic may be an important first step.

“The first thing is not to ignore it,” Dr. Heymsfield said. “Anything that can be done to prevent excess weight gain during childhood – not to promote anorexia or anything like that, but just being careful – is very important, because these behaviors are formed early in life, and they persist.”

CHOP supported the research. Dr. Jenssen and Dr. Hassink have disclosed no relevant financial relationships. Dr. Heymsfield is a medical adviser for Medifast, a weight loss company.

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

Obesity rates among children jumped substantially in the first months of the COVID-19 pandemic, according to a study published online in Pediatrics. Experts worry the excess weight will be a continuing problem for these children.

“Across the board in the span of a year, there has been a 2% increase in obesity, which is really striking,” lead author Brian P. Jenssen, MD, said in an interview.

The prevalence of obesity in a large pediatric primary care network increased from 13.7% to 15.4%.

Preexisting disparities by race or ethnicity and socioeconomic status worsened, noted Dr. Jenssen, a primary care pediatrician affiliated with Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania, Philadelphia.

Dr. Jenssen and colleagues compared the average obesity rate from June to December 2020 with the rate from June to December 2019 among patients in the CHOP Care Network, which includes 29 urban, suburban, and semirural clinics in the Philadelphia region. In June 2020, the volume of patient visits “returned to near-normal” after a dramatic decline in March 2020, the study authors wrote.

The investigators examined body mass index at all visits for patients aged 2-17 years for whom height and weight were documented. Patients with a BMI at or above the 95th percentile were classified as obese. The analysis included approximately 169,000 visits in 2019 and about 145,000 in 2020.

The average age of the patients was 9.2 years, and 48.9% were girls. In all, 21.4% were non-Hispanic Black, and about 30% were publicly insured.

Increases in obesity rates were more pronounced among patients aged 5-9 years and among patients who were Hispanic/Latino, non-Hispanic Black, publicly insured, or from lower-income neighborhoods.

Whereas the obesity rate increased 1% for patients aged 13-17 years, the rate increased 2.6% for patients aged 5-9 years.

Nearly 25% of Hispanic/Latino or non-Hispanic Black patients seen during the pandemic were obese, compared with 11.3% of non-Hispanic White patients. Before the pandemic, differences by race or ethnicity had been about 10%-11%.

Limiting the analysis to preventive visits did not meaningfully change the results, wrote Dr. Jenssen and colleagues.

“Having any increase in the obesity rates is alarming,” said Sandra Hassink, MD, medical director for the American Academy of Pediatrics’ (AAP’s) Institute for Healthy Childhood Weight. “I think what we’re seeing is what we feared.”

Before the pandemic, children received appropriately portioned breakfasts and lunches at school, but during the pandemic, they had less access to such meals, the academy noted. Disruptions to schooling, easier access to unhealthy snacks, increased screen time, and economic issues such as parents’ job losses were further factors, Hassink said.
 

Tackling the weight gain

In December 2020, the AAP issued two clinical guidance documents to highlight the importance of addressing obesity during the pandemic. Recommendations included physician counseling of families about maintaining healthy nutrition, minimizing sedentary time, and getting enough sleep and physical activity, as well as the assessment of all patients for onset of obesity and the maintenance of obesity treatment for patients with obesity.

In addition to clinical assessments and guidance, Dr. Jenssen emphasized that a return to routines may be crucial. Prepandemic studies have shown that many children, especially those insured by Medicaid, gain more weight during the summer when they are out of school, he noted. Many of the same factors are present during the pandemic, he said.

“One solution, and probably the most important solution, is getting kids back in school,” Dr. Jenssen said. School disruptions also have affected children’s learning and mental health, but those effects may be harder to quantify than BMI, he said.

Dr. Jenssen suggests that parents do their best to model good routines and habits. For example, they might decide that they and their children will stop drinking soda as a family, or opt for an apple instead of a bag of chips. They can walk around the house or up and down stairs when talking. “Those sorts of little things can make a big difference in the long run,” Dr. Jenssen said.

Clinicians should address obesity in a compassionate and caring way, be aware of community resources to help families adopt healthy lifestyles, and “look for the comorbidities of obesity,” such as type 2 diabetes, liver disease, sleep apnea, knee problems, and hypertension, Dr. Hassink said.

Policies that address other factors, such as the cost of healthy foods and the marketing of unhealthy foods, may also be needed, Dr. Hassink said.

“I’ve always thought of obesity as kind of the canary in the coal mine,” Dr. Hassink said. “It is important to keep our minds on the fact that it is a chronic disease. But it also indicates a lot of things about how we are able to support a healthy population.”
 

Potato chips, red meat, and sugary drinks

Other researchers have assessed how healthy behaviors tended to take a turn for the worse when routines were disrupted during the pandemic. Steven B. Heymsfield, MD, a professor in the metabolism and body composition laboratory at Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and collaborators documented how diet and activity changed for children during the pandemic.

Dr. Heymsfield worked with researchers in Italy to examine changes in behavior among 41 children and adolescents with obesity in Verona, Italy, during an early lockdown.

As part of a longitudinal observational study, they had baseline data about diet and physical activity from interviews conducted from May to July 2019. They repeated the interviews 3 weeks after a mandatory quarantine.

Intake of potato chips, red meat, and sugary drinks had increased, time spent in sports activities had decreased by more than 2 hours per week, and screen time had increased by more than 4 hours per day, the researchers found. Their study was published in Obesity.

Unpublished follow-up data indicate that “there was further deterioration in the diets and activity patterns” for some but not all of the participants, Dr. Heymsfield said.

He said he was hopeful that children who experienced the onset of obesity during the pandemic may lose weight when routines return to normal, but added that it is unclear whether that will happen.

“My impression from the limited written literature on this question is that for some kids who gain weight during the lockdown or, by analogy, the summer months, the weight doesn’t go back down again. It is not universal, but it is a known phenomenon that it is a bit of a ratchet,” he said. “They just sort of slowly ratchet their weights up, up to adulthood.”

Recognizing weight gain during the pandemic may be an important first step.

“The first thing is not to ignore it,” Dr. Heymsfield said. “Anything that can be done to prevent excess weight gain during childhood – not to promote anorexia or anything like that, but just being careful – is very important, because these behaviors are formed early in life, and they persist.”

CHOP supported the research. Dr. Jenssen and Dr. Hassink have disclosed no relevant financial relationships. Dr. Heymsfield is a medical adviser for Medifast, a weight loss company.

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

Background: More than a decade has passed since the last CAP guidelines. Since then there have been new trials and epidemiological studies. There have also been changes to the process for guideline development. This guideline has moved away from the narrative style of guidelines to the GRADE format and PICO framework with hopes of answering specific questions by looking at the quality of evidence.

Other recommendations include not routinely testing for urine pneumococcal or legionella antigens in nonsevere CAP; using PSI over CURB-65, in addition to clinical judgment, to determine need for inpatient care; using severe CAP criteria and clinical judgment for determining ICU need; not adding anaerobic coverage for aspiration pneumonia; and treating most cases of CAP that are clinically stable and uncomplicated for 5-7 days.

Bottom line: Given new data, updated recommendations have been made to help optimize CAP therapy.

Citation: Metlay JP et al. Diagnosis and treatment of adults with community-acquired pneumonia: An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.

Dr. Horton is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.

Background: More than a decade has passed since the last CAP guidelines. Since then there have been new trials and epidemiological studies. There have also been changes to the process for guideline development. This guideline has moved away from the narrative style of guidelines to the GRADE format and PICO framework with hopes of answering specific questions by looking at the quality of evidence.

Other recommendations include not routinely testing for urine pneumococcal or legionella antigens in nonsevere CAP; using PSI over CURB-65, in addition to clinical judgment, to determine need for inpatient care; using severe CAP criteria and clinical judgment for determining ICU need; not adding anaerobic coverage for aspiration pneumonia; and treating most cases of CAP that are clinically stable and uncomplicated for 5-7 days.

Bottom line: Given new data, updated recommendations have been made to help optimize CAP therapy.

Citation: Metlay JP et al. Diagnosis and treatment of adults with community-acquired pneumonia: An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.

Dr. Horton is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.

Background: More than a decade has passed since the last CAP guidelines. Since then there have been new trials and epidemiological studies. There have also been changes to the process for guideline development. This guideline has moved away from the narrative style of guidelines to the GRADE format and PICO framework with hopes of answering specific questions by looking at the quality of evidence.

Other recommendations include not routinely testing for urine pneumococcal or legionella antigens in nonsevere CAP; using PSI over CURB-65, in addition to clinical judgment, to determine need for inpatient care; using severe CAP criteria and clinical judgment for determining ICU need; not adding anaerobic coverage for aspiration pneumonia; and treating most cases of CAP that are clinically stable and uncomplicated for 5-7 days.

Bottom line: Given new data, updated recommendations have been made to help optimize CAP therapy.

Citation: Metlay JP et al. Diagnosis and treatment of adults with community-acquired pneumonia: An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-67.

Dr. Horton is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.

Breast cancer is the second most common malignancy in women (after primary skin cancer) and is the second leading cause of cancer-related death in this population. In 2020, the American Cancer Society reported an estimated 276,480 new breast cancer diagnoses and 42,170 breast cancer–related deaths.¹ Despite the fact that routine screening with mammography and sonography is standard, the incidence of advanced breast cancer at the time of diagnosis has remained stable over time, suggesting that life-threatening breast cancers are not being caught at an earlier stage. The number of breast cancers with distant metastases at the time of diagnosis also has not decreased.² Therefore, although screening tests are valuable, they are imperfect and not without limitations.

Cutaneous metastasis is defined as the spread of malignant cells from an internal neoplasm to the skin, which can occur either by contiguous invasion or by distant metastasis through hematogenous or lymphatic routes.³ The diagnosis of cutaneous metastasis requires a high index of suspicion on the part of the clinician.⁴ Of the various internal malignancies in women, breast cancer most frequently results in metastasis to the skin,⁵ with up to 24% of patients with metastatic breast cancer developing cutaneous lesions.⁶

In recent years, there have been multiple reports of skin lesions prompting the diagnosis of a previously unknown breast cancer. In a study by Lookingbill et al,⁶ 6.3% of patients with breast cancer presented with cutaneous involvement at the time of diagnosis, with 3.5% having skin symptoms as the presenting sign. Although there have been studies analyzing cutaneous metastasis from various internal malignancies, none thus far have focused on cutaneous metastasis as a presenting sign of breast cancer. This systematic review aimed to highlight the diverse clinical presentations of cutaneous metastatic breast cancer and their clinical implications.

Methods

Study Selection
This study utilized the PRISMA guidelines for systematic reviews.⁷ A review of the literature was conducted using the following databases: MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO.

Search Strategy and Analysis
We completed our search of each of the databases on December 16, 2017, using the phrases cutaneous metastasis and breast cancer to find relevant case reports and retrospective studies. Three authors (C.J., S.R., and M.A.) manually reviewed the resulting abstracts. If an abstract did not include enough information to determine inclusion, the full-text version was reviewed by 2 of the authors (C.J. and S.R.). Two of the authors (C.J. and M.A.) also assessed each source for relevancy and included the articles deemed eligible (Figure 1).

For a retrospective review to be included, it must have specified the number of breast cancer cases and the number of cutaneous metastases presenting initially or simultaneously to the breast cancer diagnosis. Bansal et al⁸ defined a simultaneous diagnosis as a skin lesion presenting with other concerns associated with the primary malignancy.

Results

The initial search of MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO yielded a total of 722 articles. Seven other articles found separately while undergoing our initial research were added to this total. Abstracts were manually screened, with 657 articles discarded after failing to meet the predetermined inclusion criteria. After removal of 25 duplicate articles, the full text of the remaining 47 articles were reviewed, leading to the elimination of an additional 11 articles that did not meet the necessary criteria. This resulted in 36 articles (Figure 1), including 27 individual case reports (Table 1) and 9 retrospective reviews (Table 2). Approximately 13.7% of patients in the 9 retrospective reviews presented with a skin lesion before or simultaneous to the diagnosis of breast cancer (Figure 2).

Forty-one percent (17/41) of the patients with cutaneous metastasis as a presenting feature of their breast cancer fell outside the age range for breast cancer screening recommended by the US Preventive Services Task Force,⁴² with 24% of the patients younger than 50 years and 17% older than 74 years (Figure 3).

Comment

Our systematic review demonstrated that cutaneous lesions may be the first clinical manifestation of an undetected primary malignancy.⁴⁰ These lesions often occur on the chest but may involve the face, abdomen, or extremities. Although asymptomatic erythematous nodules and plaques are the most common clinical presentations, lesions may be tender or pruritic or may even resemble benign skin conditions, including dermatitis, cellulitis, urticaria, and papulovesicular eruptions, causing them to go unrecognized.

Nevertheless, cutaneous metastasis of a visceral malignancy generally is observed late in the disease course, often following the diagnosis of a primary malignancy.¹⁴ Breast cancer is the most common internal malignancy to feature cutaneous spread, with the largest case series revealing a 23.9% rate of cutaneous metastases in females with breast carcinoma.⁶ Because of its proximity, the chest wall is the most common location for cutaneous lesions of metastatic breast cancer.

Malignant cells from a primary breast tumor may spread to the skin via lymphatic, hematogenous, or contiguous tissue dissemination, as well as iatrogenically through direct implantation during surgical procedures.³ The mechanism of neoplasm spread may likewise influence the clinical appearance of the resulting lesions. The localized lymphedema with a peau d’orange appearance of inflammatory metastatic breast carcinoma or the erythematous plaques of carcinoma erysipeloides are caused by embolized tumor cells obstructing dermal lymphatic vessels.^3,11 On the other hand, the indurated erythematous plaques of carcinoma en cuirasse are caused by diffuse cutaneous and subcutaneous infiltration of tumor cells that also may be associated with marked reduction in breast volume.³

A primary breast cancer is classically diagnosed with a combination of clinical breast examination, radiologic imaging (ultrasound, mammogram, breast magnetic resonance imaging, or computed tomography), and fine-needle aspiration or lesional biopsy with histopathology.⁹ Given that in 20% of metastasized breast cancers the primary tumor may not be identified, a negative breast examination and imaging do not rule out breast cancer, especially if cutaneous biopsy reveals a primary malignancy.⁴³ Histopathology and immunohistochemistry can thereby confirm the presence of metastatic cutaneous lesions and help characterize the breast cancer type involved, with adenocarcinomas being most commonly implicated.²⁸ Although both ductal and lobular adenocarcinomas stain positive for cytokeratin 7, estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15, carcinoembryonic antigen, and mammaglobin, only the former shows positivity for e-cadherin markers.³ Conversely, inflammatory carcinoma stains positive for CD31 and podoplanin, telangiectatic carcinoma stains positive for CD31, and mammary Paget disease stains positive for cytokeratin 7 and mucin 1, cell surface associated.³ Apart from cutaneous biopsy, fine-needle aspiration cytology can likewise provide a simple and rapid method of diagnosis with high sensitivity and specificity.¹⁴

Conclusion

Although cutaneous metastasis as the presenting sign of a breast malignancy is rare, a high index of suspicion should be exercised when encountering rapid-onset, out-of-place nodules or plaques in female patients, particularly nodules or plaques presenting on the chest.

Breast cancer is the second most common malignancy in women (after primary skin cancer) and is the second leading cause of cancer-related death in this population. In 2020, the American Cancer Society reported an estimated 276,480 new breast cancer diagnoses and 42,170 breast cancer–related deaths.¹ Despite the fact that routine screening with mammography and sonography is standard, the incidence of advanced breast cancer at the time of diagnosis has remained stable over time, suggesting that life-threatening breast cancers are not being caught at an earlier stage. The number of breast cancers with distant metastases at the time of diagnosis also has not decreased.² Therefore, although screening tests are valuable, they are imperfect and not without limitations.

Cutaneous metastasis is defined as the spread of malignant cells from an internal neoplasm to the skin, which can occur either by contiguous invasion or by distant metastasis through hematogenous or lymphatic routes.³ The diagnosis of cutaneous metastasis requires a high index of suspicion on the part of the clinician.⁴ Of the various internal malignancies in women, breast cancer most frequently results in metastasis to the skin,⁵ with up to 24% of patients with metastatic breast cancer developing cutaneous lesions.⁶

In recent years, there have been multiple reports of skin lesions prompting the diagnosis of a previously unknown breast cancer. In a study by Lookingbill et al,⁶ 6.3% of patients with breast cancer presented with cutaneous involvement at the time of diagnosis, with 3.5% having skin symptoms as the presenting sign. Although there have been studies analyzing cutaneous metastasis from various internal malignancies, none thus far have focused on cutaneous metastasis as a presenting sign of breast cancer. This systematic review aimed to highlight the diverse clinical presentations of cutaneous metastatic breast cancer and their clinical implications.

Methods

Study Selection
This study utilized the PRISMA guidelines for systematic reviews.⁷ A review of the literature was conducted using the following databases: MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO.

Search Strategy and Analysis
We completed our search of each of the databases on December 16, 2017, using the phrases cutaneous metastasis and breast cancer to find relevant case reports and retrospective studies. Three authors (C.J., S.R., and M.A.) manually reviewed the resulting abstracts. If an abstract did not include enough information to determine inclusion, the full-text version was reviewed by 2 of the authors (C.J. and S.R.). Two of the authors (C.J. and M.A.) also assessed each source for relevancy and included the articles deemed eligible (Figure 1).

For a retrospective review to be included, it must have specified the number of breast cancer cases and the number of cutaneous metastases presenting initially or simultaneously to the breast cancer diagnosis. Bansal et al⁸ defined a simultaneous diagnosis as a skin lesion presenting with other concerns associated with the primary malignancy.

Results

The initial search of MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO yielded a total of 722 articles. Seven other articles found separately while undergoing our initial research were added to this total. Abstracts were manually screened, with 657 articles discarded after failing to meet the predetermined inclusion criteria. After removal of 25 duplicate articles, the full text of the remaining 47 articles were reviewed, leading to the elimination of an additional 11 articles that did not meet the necessary criteria. This resulted in 36 articles (Figure 1), including 27 individual case reports (Table 1) and 9 retrospective reviews (Table 2). Approximately 13.7% of patients in the 9 retrospective reviews presented with a skin lesion before or simultaneous to the diagnosis of breast cancer (Figure 2).

Forty-one percent (17/41) of the patients with cutaneous metastasis as a presenting feature of their breast cancer fell outside the age range for breast cancer screening recommended by the US Preventive Services Task Force,⁴² with 24% of the patients younger than 50 years and 17% older than 74 years (Figure 3).

Comment

Our systematic review demonstrated that cutaneous lesions may be the first clinical manifestation of an undetected primary malignancy.⁴⁰ These lesions often occur on the chest but may involve the face, abdomen, or extremities. Although asymptomatic erythematous nodules and plaques are the most common clinical presentations, lesions may be tender or pruritic or may even resemble benign skin conditions, including dermatitis, cellulitis, urticaria, and papulovesicular eruptions, causing them to go unrecognized.

Nevertheless, cutaneous metastasis of a visceral malignancy generally is observed late in the disease course, often following the diagnosis of a primary malignancy.¹⁴ Breast cancer is the most common internal malignancy to feature cutaneous spread, with the largest case series revealing a 23.9% rate of cutaneous metastases in females with breast carcinoma.⁶ Because of its proximity, the chest wall is the most common location for cutaneous lesions of metastatic breast cancer.

Malignant cells from a primary breast tumor may spread to the skin via lymphatic, hematogenous, or contiguous tissue dissemination, as well as iatrogenically through direct implantation during surgical procedures.³ The mechanism of neoplasm spread may likewise influence the clinical appearance of the resulting lesions. The localized lymphedema with a peau d’orange appearance of inflammatory metastatic breast carcinoma or the erythematous plaques of carcinoma erysipeloides are caused by embolized tumor cells obstructing dermal lymphatic vessels.^3,11 On the other hand, the indurated erythematous plaques of carcinoma en cuirasse are caused by diffuse cutaneous and subcutaneous infiltration of tumor cells that also may be associated with marked reduction in breast volume.³

A primary breast cancer is classically diagnosed with a combination of clinical breast examination, radiologic imaging (ultrasound, mammogram, breast magnetic resonance imaging, or computed tomography), and fine-needle aspiration or lesional biopsy with histopathology.⁹ Given that in 20% of metastasized breast cancers the primary tumor may not be identified, a negative breast examination and imaging do not rule out breast cancer, especially if cutaneous biopsy reveals a primary malignancy.⁴³ Histopathology and immunohistochemistry can thereby confirm the presence of metastatic cutaneous lesions and help characterize the breast cancer type involved, with adenocarcinomas being most commonly implicated.²⁸ Although both ductal and lobular adenocarcinomas stain positive for cytokeratin 7, estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15, carcinoembryonic antigen, and mammaglobin, only the former shows positivity for e-cadherin markers.³ Conversely, inflammatory carcinoma stains positive for CD31 and podoplanin, telangiectatic carcinoma stains positive for CD31, and mammary Paget disease stains positive for cytokeratin 7 and mucin 1, cell surface associated.³ Apart from cutaneous biopsy, fine-needle aspiration cytology can likewise provide a simple and rapid method of diagnosis with high sensitivity and specificity.¹⁴

Conclusion

Although cutaneous metastasis as the presenting sign of a breast malignancy is rare, a high index of suspicion should be exercised when encountering rapid-onset, out-of-place nodules or plaques in female patients, particularly nodules or plaques presenting on the chest.

Breast cancer is the second most common malignancy in women (after primary skin cancer) and is the second leading cause of cancer-related death in this population. In 2020, the American Cancer Society reported an estimated 276,480 new breast cancer diagnoses and 42,170 breast cancer–related deaths.¹ Despite the fact that routine screening with mammography and sonography is standard, the incidence of advanced breast cancer at the time of diagnosis has remained stable over time, suggesting that life-threatening breast cancers are not being caught at an earlier stage. The number of breast cancers with distant metastases at the time of diagnosis also has not decreased.² Therefore, although screening tests are valuable, they are imperfect and not without limitations.

Cutaneous metastasis is defined as the spread of malignant cells from an internal neoplasm to the skin, which can occur either by contiguous invasion or by distant metastasis through hematogenous or lymphatic routes.³ The diagnosis of cutaneous metastasis requires a high index of suspicion on the part of the clinician.⁴ Of the various internal malignancies in women, breast cancer most frequently results in metastasis to the skin,⁵ with up to 24% of patients with metastatic breast cancer developing cutaneous lesions.⁶

In recent years, there have been multiple reports of skin lesions prompting the diagnosis of a previously unknown breast cancer. In a study by Lookingbill et al,⁶ 6.3% of patients with breast cancer presented with cutaneous involvement at the time of diagnosis, with 3.5% having skin symptoms as the presenting sign. Although there have been studies analyzing cutaneous metastasis from various internal malignancies, none thus far have focused on cutaneous metastasis as a presenting sign of breast cancer. This systematic review aimed to highlight the diverse clinical presentations of cutaneous metastatic breast cancer and their clinical implications.

Methods

Study Selection
This study utilized the PRISMA guidelines for systematic reviews.⁷ A review of the literature was conducted using the following databases: MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO.

Search Strategy and Analysis
We completed our search of each of the databases on December 16, 2017, using the phrases cutaneous metastasis and breast cancer to find relevant case reports and retrospective studies. Three authors (C.J., S.R., and M.A.) manually reviewed the resulting abstracts. If an abstract did not include enough information to determine inclusion, the full-text version was reviewed by 2 of the authors (C.J. and S.R.). Two of the authors (C.J. and M.A.) also assessed each source for relevancy and included the articles deemed eligible (Figure 1).

For a retrospective review to be included, it must have specified the number of breast cancer cases and the number of cutaneous metastases presenting initially or simultaneously to the breast cancer diagnosis. Bansal et al⁸ defined a simultaneous diagnosis as a skin lesion presenting with other concerns associated with the primary malignancy.

Results

The initial search of MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO yielded a total of 722 articles. Seven other articles found separately while undergoing our initial research were added to this total. Abstracts were manually screened, with 657 articles discarded after failing to meet the predetermined inclusion criteria. After removal of 25 duplicate articles, the full text of the remaining 47 articles were reviewed, leading to the elimination of an additional 11 articles that did not meet the necessary criteria. This resulted in 36 articles (Figure 1), including 27 individual case reports (Table 1) and 9 retrospective reviews (Table 2). Approximately 13.7% of patients in the 9 retrospective reviews presented with a skin lesion before or simultaneous to the diagnosis of breast cancer (Figure 2).

Forty-one percent (17/41) of the patients with cutaneous metastasis as a presenting feature of their breast cancer fell outside the age range for breast cancer screening recommended by the US Preventive Services Task Force,⁴² with 24% of the patients younger than 50 years and 17% older than 74 years (Figure 3).

Comment

Our systematic review demonstrated that cutaneous lesions may be the first clinical manifestation of an undetected primary malignancy.⁴⁰ These lesions often occur on the chest but may involve the face, abdomen, or extremities. Although asymptomatic erythematous nodules and plaques are the most common clinical presentations, lesions may be tender or pruritic or may even resemble benign skin conditions, including dermatitis, cellulitis, urticaria, and papulovesicular eruptions, causing them to go unrecognized.

Nevertheless, cutaneous metastasis of a visceral malignancy generally is observed late in the disease course, often following the diagnosis of a primary malignancy.¹⁴ Breast cancer is the most common internal malignancy to feature cutaneous spread, with the largest case series revealing a 23.9% rate of cutaneous metastases in females with breast carcinoma.⁶ Because of its proximity, the chest wall is the most common location for cutaneous lesions of metastatic breast cancer.

Malignant cells from a primary breast tumor may spread to the skin via lymphatic, hematogenous, or contiguous tissue dissemination, as well as iatrogenically through direct implantation during surgical procedures.³ The mechanism of neoplasm spread may likewise influence the clinical appearance of the resulting lesions. The localized lymphedema with a peau d’orange appearance of inflammatory metastatic breast carcinoma or the erythematous plaques of carcinoma erysipeloides are caused by embolized tumor cells obstructing dermal lymphatic vessels.^3,11 On the other hand, the indurated erythematous plaques of carcinoma en cuirasse are caused by diffuse cutaneous and subcutaneous infiltration of tumor cells that also may be associated with marked reduction in breast volume.³

A primary breast cancer is classically diagnosed with a combination of clinical breast examination, radiologic imaging (ultrasound, mammogram, breast magnetic resonance imaging, or computed tomography), and fine-needle aspiration or lesional biopsy with histopathology.⁹ Given that in 20% of metastasized breast cancers the primary tumor may not be identified, a negative breast examination and imaging do not rule out breast cancer, especially if cutaneous biopsy reveals a primary malignancy.⁴³ Histopathology and immunohistochemistry can thereby confirm the presence of metastatic cutaneous lesions and help characterize the breast cancer type involved, with adenocarcinomas being most commonly implicated.²⁸ Although both ductal and lobular adenocarcinomas stain positive for cytokeratin 7, estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15, carcinoembryonic antigen, and mammaglobin, only the former shows positivity for e-cadherin markers.³ Conversely, inflammatory carcinoma stains positive for CD31 and podoplanin, telangiectatic carcinoma stains positive for CD31, and mammary Paget disease stains positive for cytokeratin 7 and mucin 1, cell surface associated.³ Apart from cutaneous biopsy, fine-needle aspiration cytology can likewise provide a simple and rapid method of diagnosis with high sensitivity and specificity.¹⁴

Conclusion

Although cutaneous metastasis as the presenting sign of a breast malignancy is rare, a high index of suspicion should be exercised when encountering rapid-onset, out-of-place nodules or plaques in female patients, particularly nodules or plaques presenting on the chest.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

The number of new COVID-19 cases in children increased for the second consecutive week in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 64,000 new cases were reported among children for the week of March 19-25 – up from 57,000 the week before, which, in turn, marked the end of an 8-week decline in new cases. That brings the number of children infected with the coronavirus to over 3.4 million since the beginning of the pandemic, or 13.4% of all reported cases, the AAP and CHA said in their weekly COVID-19 report.

For just the week of March 19-25, however, the proportion of all cases occurring in children was quite a bit higher, 19.1%. That’s higher than at any other point during the pandemic, passing the previous high of 18.7% set just a week earlier, based on the data collected by AAP/CHA from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

The national infection rate was 4,525 cases per 100,000 children for the week of March 19-25, compared with 4,440 per 100,000 the previous week. States falling the farthest from that national mark were Hawaii at 1,101 per 100,000 and North Dakota at 8,848, the AAP and CHA said.

There was double-digit increase, 11, in the number of child deaths, as the total went from 268 to 279 despite Virginia’s revising its mortality data downward. The mortality rate for children remains 0.01%, and children represent only 0.06% of all COVID-19–related deaths in the 43 states, along with New York City, Puerto Rico, and Guam, that are reporting deaths by age, the report shows.

The state/local-level data show that Texas has the highest number of child deaths (48), followed by Arizona (26), New York City (22), California (16), and Illinois (16), while nine states and the District of Columbia have not yet reported a death, the AAP and CHA said.

[email protected]

The number of new COVID-19 cases in children increased for the second consecutive week in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 64,000 new cases were reported among children for the week of March 19-25 – up from 57,000 the week before, which, in turn, marked the end of an 8-week decline in new cases. That brings the number of children infected with the coronavirus to over 3.4 million since the beginning of the pandemic, or 13.4% of all reported cases, the AAP and CHA said in their weekly COVID-19 report.

For just the week of March 19-25, however, the proportion of all cases occurring in children was quite a bit higher, 19.1%. That’s higher than at any other point during the pandemic, passing the previous high of 18.7% set just a week earlier, based on the data collected by AAP/CHA from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

The national infection rate was 4,525 cases per 100,000 children for the week of March 19-25, compared with 4,440 per 100,000 the previous week. States falling the farthest from that national mark were Hawaii at 1,101 per 100,000 and North Dakota at 8,848, the AAP and CHA said.

There was double-digit increase, 11, in the number of child deaths, as the total went from 268 to 279 despite Virginia’s revising its mortality data downward. The mortality rate for children remains 0.01%, and children represent only 0.06% of all COVID-19–related deaths in the 43 states, along with New York City, Puerto Rico, and Guam, that are reporting deaths by age, the report shows.

The state/local-level data show that Texas has the highest number of child deaths (48), followed by Arizona (26), New York City (22), California (16), and Illinois (16), while nine states and the District of Columbia have not yet reported a death, the AAP and CHA said.

[email protected]

The number of new COVID-19 cases in children increased for the second consecutive week in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 64,000 new cases were reported among children for the week of March 19-25 – up from 57,000 the week before, which, in turn, marked the end of an 8-week decline in new cases. That brings the number of children infected with the coronavirus to over 3.4 million since the beginning of the pandemic, or 13.4% of all reported cases, the AAP and CHA said in their weekly COVID-19 report.

For just the week of March 19-25, however, the proportion of all cases occurring in children was quite a bit higher, 19.1%. That’s higher than at any other point during the pandemic, passing the previous high of 18.7% set just a week earlier, based on the data collected by AAP/CHA from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

The national infection rate was 4,525 cases per 100,000 children for the week of March 19-25, compared with 4,440 per 100,000 the previous week. States falling the farthest from that national mark were Hawaii at 1,101 per 100,000 and North Dakota at 8,848, the AAP and CHA said.

There was double-digit increase, 11, in the number of child deaths, as the total went from 268 to 279 despite Virginia’s revising its mortality data downward. The mortality rate for children remains 0.01%, and children represent only 0.06% of all COVID-19–related deaths in the 43 states, along with New York City, Puerto Rico, and Guam, that are reporting deaths by age, the report shows.

The state/local-level data show that Texas has the highest number of child deaths (48), followed by Arizona (26), New York City (22), California (16), and Illinois (16), while nine states and the District of Columbia have not yet reported a death, the AAP and CHA said.

[email protected]

The combination of ixabepilone and bevacizumab demonstrated efficacy in patients with platinum-resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in a phase 2 trial.

The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.

These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).

“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
 

Study rationale and details

Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.

At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.

Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.

After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m² on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).

Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
 

Efficacy and safety

The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.

As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.

Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.

Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.

Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
 

Comparison with AURELIA

Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.

According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.

An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.

Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”

“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”

Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.

“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.

The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.

The combination of ixabepilone and bevacizumab demonstrated efficacy in patients with platinum-resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in a phase 2 trial.

The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.

These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).

“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
 

Study rationale and details

Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.

At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.

Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.

After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m² on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).

Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
 

Efficacy and safety

The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.

As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.

Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.

Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.

Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
 

Comparison with AURELIA

Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.

According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.

An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.

Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”

“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”

Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.

“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.

The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.

The combination of ixabepilone and bevacizumab demonstrated efficacy in patients with platinum-resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in a phase 2 trial.

The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.

These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).

“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
 

Study rationale and details

Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.

At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.

Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.

After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m² on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).

Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
 

Efficacy and safety

The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.

As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.

Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.

Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.

Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
 

Comparison with AURELIA

Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.

According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.

An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.

Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”

“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”

Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.

“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.

The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.