Clinician Reviews

Despite a new meta-analysis claiming to show that testosterone replacement therapy for men with hypogonadism does not increase the risk of cardiovascular outcomes such as myocardial infarction or stroke, experts say the jury is still out.

A more definitive answer for cardiovascular safety of testosterone therapy will come from the TRAVERSE dedicated cardiovascular outcome trial, sponsored by AbbVie, which will have up to 5 years of follow-up, with results expected later this year.

The current meta-analysis by Jemma Hudson of Aberdeen (Scotland) University and colleagues was published online in The Lancet Healthy Longevity. The work will also be presented June 13 at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia, by senior author Channa Y. Jayasena, MD, PhD.

In 2014, the U.S. Food and Drug Administration mandated a label on testosterone products warning of possible increased cardiovascular risks and to reserve the therapy for symptomatic hypogonadism only. In contrast, the European Medicines Agency concluded that when hypogonadism is properly diagnosed and managed, there is currently no clear, consistent evidence that testosterone therapy causes increased cardiovascular risk.

To address this uncertainty, Dr. Hudson and colleagues formed a global collaborative to obtain individual patient data on cardiovascular outcomes from randomized controlled trials of testosterone therapy for men with hypogonadism.

They pooled data from 35 trials published from 1992 to Aug. 27, 2018, including 17 trials (3,431 patients) for which the researchers obtained patient-level data. The individual trials were 3-12 months long, except for one 3-year trial.

During a mean follow-up of 9.5 months, there was no significant increase in cardiovascular outcomes in men randomized to testosterone therapy versus placebo (odds ratio, 1.07; P = .62), nor were there any significantly increased risks of death, stroke, or different types of cardiovascular outcome, although those numbers were small.  

This is “the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism,” according to the researchers. “The current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism,” they conclude.

However, they also acknowledge that “long-term data are needed to fully evaluate the safety of testosterone.”

Erin D. Michos, MD, coauthor of an accompanying editorial, told this news organization, “This study doesn’t say to me that low testosterone necessarily needs to be treated. It’s still not indicated in people just for a low number [for blood testosterone] with less-severe symptoms. It really comes down to each individual person, how symptomatic they are, and their cardiovascular risk.”

‘Trial is not definitive’

Dr. Michos is not the only person to be skeptical. Together with Steven Nissen, MD, an investigator for the TRAVERSE trial, she agrees that this new evidence is not yet decisive, largely because the individual trials in the meta-analysis were short and not designed as cardiovascular outcome trials.

Dr. Nissen, a cardiologist at Cleveland Clinic, added that the individual trials were heterogeneous, with “very few real cardiovascular events,” so the meta-analysis “is not definitive,” he said in an interview.

While this meta-analysis “that pooled together a lot of smaller studies is reassuring that there’s no signal of harm, it’s really inconclusive because the follow-up was really short – a mean of only 9.5 months – and you really need a larger study with longer follow up to be more conclusive,” Dr. Michos noted.

“We should have more data soon” from TRAVERSE, said Dr. Michos, from the division of cardiology, Johns Hopkins University, Baltimore, who is not involved with that study.

Meanwhile, “I don’t think [this analysis] changes the current recommendations,” she said.

“We should continue to use caution as indicated by the FDA label and only use testosterone therapy selectively in people who have true symptoms of hypogonadism,” and be cautious about using it particularly in men at higher cardiovascular risk because of family history or known personal heart disease.

On the other hand, the meta-analysis did not show harm, she noted, “so we don’t necessarily need to pull patients off therapy if they are already taking it. But I wouldn’t right now just start new patients on it unless they had a strong indication.”

“Certainly, great caution is advised regarding the use of testosterone replacement therapy in people with established atherosclerosis due to the findings of plaque progression in the testosterone trials and the excess cardiovascular events observed in the TOM trial, write Dr. Michos and fellow editorialist Matthew J. Budoff, MD, of University of California, Los Angeles, in their editorial.
 

Earlier data inconclusive

Testosterone concentrations progressively decline in men with advancing age, at about 2% per year, Dr. Michos and Dr. Budoff write. In addition, men with obesity or with diabetes have low levels of testosterone, Dr. Michos noted.

Low testosterone blood levels have been associated with insulin resistance, inflammation, dyslipidemia, and atherosclerosis. Testosterone replacement therapy has been used to increase libido, improve erectile dysfunction, and boost energy levels, mood, and muscle strength.

But it is well known that testosterone increases hematocrit, which has the potential to increase the risk of venous thromboembolism.

Two large observational studies have reported increased risks of myocardial infarction, stroke, and death in men taking testosterone, compared with nonusers, but the study designs have been widely criticized, Dr. Hudson and coauthors say in their article.  

A placebo-controlled trial was stopped early by its data- and safety-monitoring board following increased cardiovascular events in men aged 65 and older who received 6 months of testosterone. Other controlled trials have not observed these effects, but none was sufficiently powered.
 

Meta-analysis results

Dr. Hudson and colleagues performed a meta-analysis of 35 trials in 5,601 men aged 18 years and older with low baseline testosterone (≤ 350 nmol/dL) who had been randomized to testosterone replacement therapy or placebo for at least 3 months, for which there were data on mortality, stroke, and cardiovascular outcomes.

The men were a mean age of 65, had a mean body mass index of 30 kg/m², and most (88%) were White. A quarter had angina, 8% had a previous myocardial infarction, and 27% had diabetes. 

Cardiovascular and cerebrovascular outcomes were not primary outcomes.

During a mean follow-up of 9.5 months, in the 13 trials that provided this information, the rate of cardiovascular events was similar in the men who received testosterone (120/1,601, 7.5%) compared with those who received placebo (110/1,519, 7.2%).

In the 14 trials that provided this information, fewer deaths were reported during testosterone treatment (6/1,621, 0.4%) than during placebo treatment (12/1,537, 0.8%), but these numbers were too small to establish whether testosterone reduced mortality risk.

The most common cardiovascular events were arrhythmia, followed by coronary heart disease, heart failure, and myocardial infarction.

Patient age, baseline testosterone, smoking status, or diabetes status were not associated with cardiovascular risk.

The only detected adverse effects were edema and a modest lowering of HDL cholesterol.

“Men who develop sexual dysfunction, unexplained anemia, or osteoporosis should be tested for low testosterone,” senior author of the meta-analysis Dr. Jayasena said in an email to this news organization.

However, Dr. Jayasena added, “Mass screening for testosterone has no benefit in asymptomatic men.”

“Older men may still benefit from testosterone, but only if they have the clinical features [of hypogonadism] and low testosterone levels,” he concluded.  

The current study is supported by the Health Technology Assessment program of the National Institute for Health Research. The TRAVERSE trial is sponsored by AbbVie. Dr. Jayasena has reported receiving research grants from LogixX Pharma. Dr. Hudson has reported no relevant financial relationships. Disclosures for the other authors are listed in the article. Dr. Michos has reported receiving support from the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine and serving on medical advisory boards for Novartis, Esperion, Amarin, and AstraZeneca outside the submitted work. Dr. Budoff has reported receiving grant support from General Electric.
 

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

Despite a new meta-analysis claiming to show that testosterone replacement therapy for men with hypogonadism does not increase the risk of cardiovascular outcomes such as myocardial infarction or stroke, experts say the jury is still out.

A more definitive answer for cardiovascular safety of testosterone therapy will come from the TRAVERSE dedicated cardiovascular outcome trial, sponsored by AbbVie, which will have up to 5 years of follow-up, with results expected later this year.

The current meta-analysis by Jemma Hudson of Aberdeen (Scotland) University and colleagues was published online in The Lancet Healthy Longevity. The work will also be presented June 13 at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia, by senior author Channa Y. Jayasena, MD, PhD.

In 2014, the U.S. Food and Drug Administration mandated a label on testosterone products warning of possible increased cardiovascular risks and to reserve the therapy for symptomatic hypogonadism only. In contrast, the European Medicines Agency concluded that when hypogonadism is properly diagnosed and managed, there is currently no clear, consistent evidence that testosterone therapy causes increased cardiovascular risk.

To address this uncertainty, Dr. Hudson and colleagues formed a global collaborative to obtain individual patient data on cardiovascular outcomes from randomized controlled trials of testosterone therapy for men with hypogonadism.

They pooled data from 35 trials published from 1992 to Aug. 27, 2018, including 17 trials (3,431 patients) for which the researchers obtained patient-level data. The individual trials were 3-12 months long, except for one 3-year trial.

During a mean follow-up of 9.5 months, there was no significant increase in cardiovascular outcomes in men randomized to testosterone therapy versus placebo (odds ratio, 1.07; P = .62), nor were there any significantly increased risks of death, stroke, or different types of cardiovascular outcome, although those numbers were small.  

This is “the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism,” according to the researchers. “The current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism,” they conclude.

However, they also acknowledge that “long-term data are needed to fully evaluate the safety of testosterone.”

Erin D. Michos, MD, coauthor of an accompanying editorial, told this news organization, “This study doesn’t say to me that low testosterone necessarily needs to be treated. It’s still not indicated in people just for a low number [for blood testosterone] with less-severe symptoms. It really comes down to each individual person, how symptomatic they are, and their cardiovascular risk.”

‘Trial is not definitive’

Dr. Michos is not the only person to be skeptical. Together with Steven Nissen, MD, an investigator for the TRAVERSE trial, she agrees that this new evidence is not yet decisive, largely because the individual trials in the meta-analysis were short and not designed as cardiovascular outcome trials.

Dr. Nissen, a cardiologist at Cleveland Clinic, added that the individual trials were heterogeneous, with “very few real cardiovascular events,” so the meta-analysis “is not definitive,” he said in an interview.

While this meta-analysis “that pooled together a lot of smaller studies is reassuring that there’s no signal of harm, it’s really inconclusive because the follow-up was really short – a mean of only 9.5 months – and you really need a larger study with longer follow up to be more conclusive,” Dr. Michos noted.

“We should have more data soon” from TRAVERSE, said Dr. Michos, from the division of cardiology, Johns Hopkins University, Baltimore, who is not involved with that study.

Meanwhile, “I don’t think [this analysis] changes the current recommendations,” she said.

“We should continue to use caution as indicated by the FDA label and only use testosterone therapy selectively in people who have true symptoms of hypogonadism,” and be cautious about using it particularly in men at higher cardiovascular risk because of family history or known personal heart disease.

On the other hand, the meta-analysis did not show harm, she noted, “so we don’t necessarily need to pull patients off therapy if they are already taking it. But I wouldn’t right now just start new patients on it unless they had a strong indication.”

“Certainly, great caution is advised regarding the use of testosterone replacement therapy in people with established atherosclerosis due to the findings of plaque progression in the testosterone trials and the excess cardiovascular events observed in the TOM trial, write Dr. Michos and fellow editorialist Matthew J. Budoff, MD, of University of California, Los Angeles, in their editorial.
 

Earlier data inconclusive

Testosterone concentrations progressively decline in men with advancing age, at about 2% per year, Dr. Michos and Dr. Budoff write. In addition, men with obesity or with diabetes have low levels of testosterone, Dr. Michos noted.

Low testosterone blood levels have been associated with insulin resistance, inflammation, dyslipidemia, and atherosclerosis. Testosterone replacement therapy has been used to increase libido, improve erectile dysfunction, and boost energy levels, mood, and muscle strength.

But it is well known that testosterone increases hematocrit, which has the potential to increase the risk of venous thromboembolism.

Two large observational studies have reported increased risks of myocardial infarction, stroke, and death in men taking testosterone, compared with nonusers, but the study designs have been widely criticized, Dr. Hudson and coauthors say in their article.  

A placebo-controlled trial was stopped early by its data- and safety-monitoring board following increased cardiovascular events in men aged 65 and older who received 6 months of testosterone. Other controlled trials have not observed these effects, but none was sufficiently powered.
 

Meta-analysis results

Dr. Hudson and colleagues performed a meta-analysis of 35 trials in 5,601 men aged 18 years and older with low baseline testosterone (≤ 350 nmol/dL) who had been randomized to testosterone replacement therapy or placebo for at least 3 months, for which there were data on mortality, stroke, and cardiovascular outcomes.

The men were a mean age of 65, had a mean body mass index of 30 kg/m², and most (88%) were White. A quarter had angina, 8% had a previous myocardial infarction, and 27% had diabetes. 

Cardiovascular and cerebrovascular outcomes were not primary outcomes.

During a mean follow-up of 9.5 months, in the 13 trials that provided this information, the rate of cardiovascular events was similar in the men who received testosterone (120/1,601, 7.5%) compared with those who received placebo (110/1,519, 7.2%).

In the 14 trials that provided this information, fewer deaths were reported during testosterone treatment (6/1,621, 0.4%) than during placebo treatment (12/1,537, 0.8%), but these numbers were too small to establish whether testosterone reduced mortality risk.

The most common cardiovascular events were arrhythmia, followed by coronary heart disease, heart failure, and myocardial infarction.

Patient age, baseline testosterone, smoking status, or diabetes status were not associated with cardiovascular risk.

The only detected adverse effects were edema and a modest lowering of HDL cholesterol.

“Men who develop sexual dysfunction, unexplained anemia, or osteoporosis should be tested for low testosterone,” senior author of the meta-analysis Dr. Jayasena said in an email to this news organization.

However, Dr. Jayasena added, “Mass screening for testosterone has no benefit in asymptomatic men.”

“Older men may still benefit from testosterone, but only if they have the clinical features [of hypogonadism] and low testosterone levels,” he concluded.  

The current study is supported by the Health Technology Assessment program of the National Institute for Health Research. The TRAVERSE trial is sponsored by AbbVie. Dr. Jayasena has reported receiving research grants from LogixX Pharma. Dr. Hudson has reported no relevant financial relationships. Disclosures for the other authors are listed in the article. Dr. Michos has reported receiving support from the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine and serving on medical advisory boards for Novartis, Esperion, Amarin, and AstraZeneca outside the submitted work. Dr. Budoff has reported receiving grant support from General Electric.
 

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

Despite a new meta-analysis claiming to show that testosterone replacement therapy for men with hypogonadism does not increase the risk of cardiovascular outcomes such as myocardial infarction or stroke, experts say the jury is still out.

A more definitive answer for cardiovascular safety of testosterone therapy will come from the TRAVERSE dedicated cardiovascular outcome trial, sponsored by AbbVie, which will have up to 5 years of follow-up, with results expected later this year.

The current meta-analysis by Jemma Hudson of Aberdeen (Scotland) University and colleagues was published online in The Lancet Healthy Longevity. The work will also be presented June 13 at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia, by senior author Channa Y. Jayasena, MD, PhD.

In 2014, the U.S. Food and Drug Administration mandated a label on testosterone products warning of possible increased cardiovascular risks and to reserve the therapy for symptomatic hypogonadism only. In contrast, the European Medicines Agency concluded that when hypogonadism is properly diagnosed and managed, there is currently no clear, consistent evidence that testosterone therapy causes increased cardiovascular risk.

To address this uncertainty, Dr. Hudson and colleagues formed a global collaborative to obtain individual patient data on cardiovascular outcomes from randomized controlled trials of testosterone therapy for men with hypogonadism.

They pooled data from 35 trials published from 1992 to Aug. 27, 2018, including 17 trials (3,431 patients) for which the researchers obtained patient-level data. The individual trials were 3-12 months long, except for one 3-year trial.

During a mean follow-up of 9.5 months, there was no significant increase in cardiovascular outcomes in men randomized to testosterone therapy versus placebo (odds ratio, 1.07; P = .62), nor were there any significantly increased risks of death, stroke, or different types of cardiovascular outcome, although those numbers were small.  

This is “the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism,” according to the researchers. “The current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism,” they conclude.

However, they also acknowledge that “long-term data are needed to fully evaluate the safety of testosterone.”

Erin D. Michos, MD, coauthor of an accompanying editorial, told this news organization, “This study doesn’t say to me that low testosterone necessarily needs to be treated. It’s still not indicated in people just for a low number [for blood testosterone] with less-severe symptoms. It really comes down to each individual person, how symptomatic they are, and their cardiovascular risk.”

‘Trial is not definitive’

Dr. Michos is not the only person to be skeptical. Together with Steven Nissen, MD, an investigator for the TRAVERSE trial, she agrees that this new evidence is not yet decisive, largely because the individual trials in the meta-analysis were short and not designed as cardiovascular outcome trials.

Dr. Nissen, a cardiologist at Cleveland Clinic, added that the individual trials were heterogeneous, with “very few real cardiovascular events,” so the meta-analysis “is not definitive,” he said in an interview.

While this meta-analysis “that pooled together a lot of smaller studies is reassuring that there’s no signal of harm, it’s really inconclusive because the follow-up was really short – a mean of only 9.5 months – and you really need a larger study with longer follow up to be more conclusive,” Dr. Michos noted.

“We should have more data soon” from TRAVERSE, said Dr. Michos, from the division of cardiology, Johns Hopkins University, Baltimore, who is not involved with that study.

Meanwhile, “I don’t think [this analysis] changes the current recommendations,” she said.

“We should continue to use caution as indicated by the FDA label and only use testosterone therapy selectively in people who have true symptoms of hypogonadism,” and be cautious about using it particularly in men at higher cardiovascular risk because of family history or known personal heart disease.

On the other hand, the meta-analysis did not show harm, she noted, “so we don’t necessarily need to pull patients off therapy if they are already taking it. But I wouldn’t right now just start new patients on it unless they had a strong indication.”

“Certainly, great caution is advised regarding the use of testosterone replacement therapy in people with established atherosclerosis due to the findings of plaque progression in the testosterone trials and the excess cardiovascular events observed in the TOM trial, write Dr. Michos and fellow editorialist Matthew J. Budoff, MD, of University of California, Los Angeles, in their editorial.
 

Earlier data inconclusive

Testosterone concentrations progressively decline in men with advancing age, at about 2% per year, Dr. Michos and Dr. Budoff write. In addition, men with obesity or with diabetes have low levels of testosterone, Dr. Michos noted.

Low testosterone blood levels have been associated with insulin resistance, inflammation, dyslipidemia, and atherosclerosis. Testosterone replacement therapy has been used to increase libido, improve erectile dysfunction, and boost energy levels, mood, and muscle strength.

But it is well known that testosterone increases hematocrit, which has the potential to increase the risk of venous thromboembolism.

Two large observational studies have reported increased risks of myocardial infarction, stroke, and death in men taking testosterone, compared with nonusers, but the study designs have been widely criticized, Dr. Hudson and coauthors say in their article.  

A placebo-controlled trial was stopped early by its data- and safety-monitoring board following increased cardiovascular events in men aged 65 and older who received 6 months of testosterone. Other controlled trials have not observed these effects, but none was sufficiently powered.
 

Meta-analysis results

Dr. Hudson and colleagues performed a meta-analysis of 35 trials in 5,601 men aged 18 years and older with low baseline testosterone (≤ 350 nmol/dL) who had been randomized to testosterone replacement therapy or placebo for at least 3 months, for which there were data on mortality, stroke, and cardiovascular outcomes.

The men were a mean age of 65, had a mean body mass index of 30 kg/m², and most (88%) were White. A quarter had angina, 8% had a previous myocardial infarction, and 27% had diabetes. 

Cardiovascular and cerebrovascular outcomes were not primary outcomes.

During a mean follow-up of 9.5 months, in the 13 trials that provided this information, the rate of cardiovascular events was similar in the men who received testosterone (120/1,601, 7.5%) compared with those who received placebo (110/1,519, 7.2%).

In the 14 trials that provided this information, fewer deaths were reported during testosterone treatment (6/1,621, 0.4%) than during placebo treatment (12/1,537, 0.8%), but these numbers were too small to establish whether testosterone reduced mortality risk.

The most common cardiovascular events were arrhythmia, followed by coronary heart disease, heart failure, and myocardial infarction.

Patient age, baseline testosterone, smoking status, or diabetes status were not associated with cardiovascular risk.

The only detected adverse effects were edema and a modest lowering of HDL cholesterol.

“Men who develop sexual dysfunction, unexplained anemia, or osteoporosis should be tested for low testosterone,” senior author of the meta-analysis Dr. Jayasena said in an email to this news organization.

However, Dr. Jayasena added, “Mass screening for testosterone has no benefit in asymptomatic men.”

“Older men may still benefit from testosterone, but only if they have the clinical features [of hypogonadism] and low testosterone levels,” he concluded.  

The current study is supported by the Health Technology Assessment program of the National Institute for Health Research. The TRAVERSE trial is sponsored by AbbVie. Dr. Jayasena has reported receiving research grants from LogixX Pharma. Dr. Hudson has reported no relevant financial relationships. Disclosures for the other authors are listed in the article. Dr. Michos has reported receiving support from the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine and serving on medical advisory boards for Novartis, Esperion, Amarin, and AstraZeneca outside the submitted work. Dr. Budoff has reported receiving grant support from General Electric.
 

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.

Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.

The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m², and weight at least 176 pounds in a randomized study.

After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.

At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.

Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.

Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.

The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.

The authors wrote: “The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease).”

A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).

No differences found between groups

“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.

More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).

Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.

The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.

Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”

“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”

“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.

She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.

She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.

The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.

Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).

Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.

Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.

Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.

The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m², and weight at least 176 pounds in a randomized study.

After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.

At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.

Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.

Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.

The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.

The authors wrote: “The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease).”

A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).

No differences found between groups

“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.

More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).

Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.

The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.

Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”

“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”

“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.

She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.

She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.

The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.

Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).

Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.

Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.

Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.

The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m², and weight at least 176 pounds in a randomized study.

After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.

At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.

Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.

Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.

The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.

The authors wrote: “The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease).”

A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).

No differences found between groups

“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.

More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).

Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.

The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.

Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”

“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”

“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.

She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.

She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.

The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.

Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).

Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.

CHARLOTTE, N.C. – Sleep and alcohol consumption in young adults seems to follow a “vicious cycle,” as one observer called it. Young adults those who drink more go to bed later, sleep less, and have worse-quality sleep than those who drink less, and those who went to bed earlier and slept longer tended to drink less the next day, a study of drinking and sleeping habits in 21- to 29-year-olds found.

“Sleep is a potential factor that we could intervene on to really identify how to improve drinking behaviors among young adults,” David Reichenberger, a graduate student at Penn State University, University Park, said in an interview after he presented his findings at the annual meeting of the Associated Professional Sleep Societies.

This is one of the few studies of alcohol consumption and sleep patterns that used an objective measure of alcohol consumption, Mr. Reichenberger said. The study evaluated sleep and alcohol consumption patterns in 222 regularly drinking young adults over 6 consecutive days. Study participants completed morning smartphone-based questionnaires, reporting their previous night’s bedtime, sleep duration, sleep quality, and number of drinks consumed. They also wore an alcohol monitor that continuously measured their transdermal alcohol consumption (TAC).

The study analyzed the data using two sets of multilevel models: A linear model that looked at how each drinking predictor was associated with each sleep variable and a Poisson model to determine how sleep predicted next-day alcohol use.

“We found that higher average peak TAC – that is, how intoxicated they got – was associated with a 19-minute later bedtime among young adults,” Mr. Reichenberger said. “Later bedtimes were then associated with a 26% greater TAC among those adults” (P < .02).
 

Patterns of alcohol consumption and sleep

On days when participants recorded a higher peak TAC, bedtime was delayed, sleep duration was shorter, and subjective sleep quality was worse, he said. However, none of the sleep variables predicted next-day peak TAC.

“We found an association between the duration of the drinking episode and later bedtimes among young adults,” he added. “And on days when the drinking episodes were longer, subsequent sleep was delayed and sleep quality was worse. But we also found that after nights when they had a later bedtime, next-day drinking episodes were about 7% longer.”

Conversely, young adults who had earlier bedtimes and longer sleep durations tended to consume fewer drinks and they achieved lower intoxication levels the next day, Mr. Reichenberger said.

Between-person results showed that young adults who tended to go to bed later drank on average 24% more the next day (P < .01). Also, each extra hour of sleep was associated with a 14% decrease in drinking the next day (P < .03).

Participants who drank more went to bed on average 12-19 minutes later (P < .01) and slept 5 fewer minutes (P < .01). Within-person results showed that on nights when participants drank more than usual they went to bed 8-13 minutes later (P < .01), slept 2-4 fewer minutes (P < .03), and had worse sleep quality (P < .01).

Mr. Reichenberger acknowledged one limitation of the study: Measuring sleep and alcohol consumption patterns over 6 days might not be long enough. Future studies should address that.
 

A ‘vicious cycle’

Hans P.A. Van Dongen, PhD, director of the Sleep and Performance Research Center at Washington State University, Spokane, said in an interview that the findings imply a “vicious cycle” between sleep and alcohol consumption. “You create a problem and then it perpetuates itself or reinforces itself.”

In older adults, alcohol tends to act as a “sleep aid,” Dr. Van Dongen noted. “Then it disrupts their sleep later on and then the next night they need to use the sleep aid again because they had a really poor night and they’re tired and they want to fall asleep.”

He added: “I think what is new here is that’s not very likely the mechanism that they’re using alcohol as a sleep aid in younger adults that we see in older adults, so I think there is a new element to it. Now does anybody know how that works exactly? No, that’s the next thing.”

The Penn State study identifies “a signal there that needs to be followed up on,” Dr. Van Dongen said. “There’s something nature’s trying to tell us but it’s not exactly clear what it’s trying to tell us.”

The National Institute on Drug Abuse provided funding for the study. Mr. Reichenberger has no relevant disclosures. Dr. Van Dongen has no disclosures to report.

CHARLOTTE, N.C. – Sleep and alcohol consumption in young adults seems to follow a “vicious cycle,” as one observer called it. Young adults those who drink more go to bed later, sleep less, and have worse-quality sleep than those who drink less, and those who went to bed earlier and slept longer tended to drink less the next day, a study of drinking and sleeping habits in 21- to 29-year-olds found.

“Sleep is a potential factor that we could intervene on to really identify how to improve drinking behaviors among young adults,” David Reichenberger, a graduate student at Penn State University, University Park, said in an interview after he presented his findings at the annual meeting of the Associated Professional Sleep Societies.

This is one of the few studies of alcohol consumption and sleep patterns that used an objective measure of alcohol consumption, Mr. Reichenberger said. The study evaluated sleep and alcohol consumption patterns in 222 regularly drinking young adults over 6 consecutive days. Study participants completed morning smartphone-based questionnaires, reporting their previous night’s bedtime, sleep duration, sleep quality, and number of drinks consumed. They also wore an alcohol monitor that continuously measured their transdermal alcohol consumption (TAC).

The study analyzed the data using two sets of multilevel models: A linear model that looked at how each drinking predictor was associated with each sleep variable and a Poisson model to determine how sleep predicted next-day alcohol use.

“We found that higher average peak TAC – that is, how intoxicated they got – was associated with a 19-minute later bedtime among young adults,” Mr. Reichenberger said. “Later bedtimes were then associated with a 26% greater TAC among those adults” (P < .02).
 

Patterns of alcohol consumption and sleep

On days when participants recorded a higher peak TAC, bedtime was delayed, sleep duration was shorter, and subjective sleep quality was worse, he said. However, none of the sleep variables predicted next-day peak TAC.

“We found an association between the duration of the drinking episode and later bedtimes among young adults,” he added. “And on days when the drinking episodes were longer, subsequent sleep was delayed and sleep quality was worse. But we also found that after nights when they had a later bedtime, next-day drinking episodes were about 7% longer.”

Conversely, young adults who had earlier bedtimes and longer sleep durations tended to consume fewer drinks and they achieved lower intoxication levels the next day, Mr. Reichenberger said.

Between-person results showed that young adults who tended to go to bed later drank on average 24% more the next day (P < .01). Also, each extra hour of sleep was associated with a 14% decrease in drinking the next day (P < .03).

Participants who drank more went to bed on average 12-19 minutes later (P < .01) and slept 5 fewer minutes (P < .01). Within-person results showed that on nights when participants drank more than usual they went to bed 8-13 minutes later (P < .01), slept 2-4 fewer minutes (P < .03), and had worse sleep quality (P < .01).

Mr. Reichenberger acknowledged one limitation of the study: Measuring sleep and alcohol consumption patterns over 6 days might not be long enough. Future studies should address that.
 

A ‘vicious cycle’

Hans P.A. Van Dongen, PhD, director of the Sleep and Performance Research Center at Washington State University, Spokane, said in an interview that the findings imply a “vicious cycle” between sleep and alcohol consumption. “You create a problem and then it perpetuates itself or reinforces itself.”

In older adults, alcohol tends to act as a “sleep aid,” Dr. Van Dongen noted. “Then it disrupts their sleep later on and then the next night they need to use the sleep aid again because they had a really poor night and they’re tired and they want to fall asleep.”

He added: “I think what is new here is that’s not very likely the mechanism that they’re using alcohol as a sleep aid in younger adults that we see in older adults, so I think there is a new element to it. Now does anybody know how that works exactly? No, that’s the next thing.”

The Penn State study identifies “a signal there that needs to be followed up on,” Dr. Van Dongen said. “There’s something nature’s trying to tell us but it’s not exactly clear what it’s trying to tell us.”

The National Institute on Drug Abuse provided funding for the study. Mr. Reichenberger has no relevant disclosures. Dr. Van Dongen has no disclosures to report.

CHARLOTTE, N.C. – Sleep and alcohol consumption in young adults seems to follow a “vicious cycle,” as one observer called it. Young adults those who drink more go to bed later, sleep less, and have worse-quality sleep than those who drink less, and those who went to bed earlier and slept longer tended to drink less the next day, a study of drinking and sleeping habits in 21- to 29-year-olds found.

“Sleep is a potential factor that we could intervene on to really identify how to improve drinking behaviors among young adults,” David Reichenberger, a graduate student at Penn State University, University Park, said in an interview after he presented his findings at the annual meeting of the Associated Professional Sleep Societies.

This is one of the few studies of alcohol consumption and sleep patterns that used an objective measure of alcohol consumption, Mr. Reichenberger said. The study evaluated sleep and alcohol consumption patterns in 222 regularly drinking young adults over 6 consecutive days. Study participants completed morning smartphone-based questionnaires, reporting their previous night’s bedtime, sleep duration, sleep quality, and number of drinks consumed. They also wore an alcohol monitor that continuously measured their transdermal alcohol consumption (TAC).

The study analyzed the data using two sets of multilevel models: A linear model that looked at how each drinking predictor was associated with each sleep variable and a Poisson model to determine how sleep predicted next-day alcohol use.

“We found that higher average peak TAC – that is, how intoxicated they got – was associated with a 19-minute later bedtime among young adults,” Mr. Reichenberger said. “Later bedtimes were then associated with a 26% greater TAC among those adults” (P < .02).
 

Patterns of alcohol consumption and sleep

On days when participants recorded a higher peak TAC, bedtime was delayed, sleep duration was shorter, and subjective sleep quality was worse, he said. However, none of the sleep variables predicted next-day peak TAC.

“We found an association between the duration of the drinking episode and later bedtimes among young adults,” he added. “And on days when the drinking episodes were longer, subsequent sleep was delayed and sleep quality was worse. But we also found that after nights when they had a later bedtime, next-day drinking episodes were about 7% longer.”

Conversely, young adults who had earlier bedtimes and longer sleep durations tended to consume fewer drinks and they achieved lower intoxication levels the next day, Mr. Reichenberger said.

Between-person results showed that young adults who tended to go to bed later drank on average 24% more the next day (P < .01). Also, each extra hour of sleep was associated with a 14% decrease in drinking the next day (P < .03).

Participants who drank more went to bed on average 12-19 minutes later (P < .01) and slept 5 fewer minutes (P < .01). Within-person results showed that on nights when participants drank more than usual they went to bed 8-13 minutes later (P < .01), slept 2-4 fewer minutes (P < .03), and had worse sleep quality (P < .01).

Mr. Reichenberger acknowledged one limitation of the study: Measuring sleep and alcohol consumption patterns over 6 days might not be long enough. Future studies should address that.
 

A ‘vicious cycle’

Hans P.A. Van Dongen, PhD, director of the Sleep and Performance Research Center at Washington State University, Spokane, said in an interview that the findings imply a “vicious cycle” between sleep and alcohol consumption. “You create a problem and then it perpetuates itself or reinforces itself.”

In older adults, alcohol tends to act as a “sleep aid,” Dr. Van Dongen noted. “Then it disrupts their sleep later on and then the next night they need to use the sleep aid again because they had a really poor night and they’re tired and they want to fall asleep.”

He added: “I think what is new here is that’s not very likely the mechanism that they’re using alcohol as a sleep aid in younger adults that we see in older adults, so I think there is a new element to it. Now does anybody know how that works exactly? No, that’s the next thing.”

The Penn State study identifies “a signal there that needs to be followed up on,” Dr. Van Dongen said. “There’s something nature’s trying to tell us but it’s not exactly clear what it’s trying to tell us.”

The National Institute on Drug Abuse provided funding for the study. Mr. Reichenberger has no relevant disclosures. Dr. Van Dongen has no disclosures to report.

A Missouri lawsuit adds a new twist to the kind of “bodily harm” in a car that’s covered by insurance.

On June 7, a three-judge panel of the state’s Court of Appeals, Western District, affirmed a $5.2 million settlement by a woman who caught a sexually transmitted disease from her former boyfriend in his car.

The woman, identified in court documents as M.O., said she contracted human papillomavirus from her boyfriend. She said he knew he had the disease but didn’t tell her.

An arbitrator found in May 2021 that the in-car sex had “directly caused, or directly contributed to cause” the STD transmission. The man was found liable. The woman was awarded $5.2 million to be paid by GEICO, which insured the man’s vehicle.

GEICO filed for the award to be overturned, alleging it had been denied due process and that the arbitration deal was unenforceable.

Court documents show that GEICO claimed the man’s policy covered only injuries that came “out of the ownership, maintenance or use of the ... auto” and that the woman’s “injuries arose from an intervening cause – namely, her failure to prevent transmission of STDs by having unprotected sex.”

The state appellate panel ruled that the lower court made no mistake in the case and upheld the decision.

The Kansas City Star reported that one of the judges concurred but said GEICO was offered “no meaningful opportunity to participate” in the lawsuit and existing law “relegat(es) the insurer to the status of a bystander.”

“This case presents novel and potentially important issues about whether an insurance carrier can be held liable under such policies for the consequences of two adults voluntarily having unprotected sex in the insured’s automobile,” noted U.S. Magistrate Judge Angel D. Mitchell in court documents. “Interpretation of these policies could have far-reaching implications for other policies with similar terms.”

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

A Missouri lawsuit adds a new twist to the kind of “bodily harm” in a car that’s covered by insurance.

On June 7, a three-judge panel of the state’s Court of Appeals, Western District, affirmed a $5.2 million settlement by a woman who caught a sexually transmitted disease from her former boyfriend in his car.

The woman, identified in court documents as M.O., said she contracted human papillomavirus from her boyfriend. She said he knew he had the disease but didn’t tell her.

An arbitrator found in May 2021 that the in-car sex had “directly caused, or directly contributed to cause” the STD transmission. The man was found liable. The woman was awarded $5.2 million to be paid by GEICO, which insured the man’s vehicle.

GEICO filed for the award to be overturned, alleging it had been denied due process and that the arbitration deal was unenforceable.

Court documents show that GEICO claimed the man’s policy covered only injuries that came “out of the ownership, maintenance or use of the ... auto” and that the woman’s “injuries arose from an intervening cause – namely, her failure to prevent transmission of STDs by having unprotected sex.”

The state appellate panel ruled that the lower court made no mistake in the case and upheld the decision.

The Kansas City Star reported that one of the judges concurred but said GEICO was offered “no meaningful opportunity to participate” in the lawsuit and existing law “relegat(es) the insurer to the status of a bystander.”

“This case presents novel and potentially important issues about whether an insurance carrier can be held liable under such policies for the consequences of two adults voluntarily having unprotected sex in the insured’s automobile,” noted U.S. Magistrate Judge Angel D. Mitchell in court documents. “Interpretation of these policies could have far-reaching implications for other policies with similar terms.”

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

A Missouri lawsuit adds a new twist to the kind of “bodily harm” in a car that’s covered by insurance.

On June 7, a three-judge panel of the state’s Court of Appeals, Western District, affirmed a $5.2 million settlement by a woman who caught a sexually transmitted disease from her former boyfriend in his car.

The woman, identified in court documents as M.O., said she contracted human papillomavirus from her boyfriend. She said he knew he had the disease but didn’t tell her.

An arbitrator found in May 2021 that the in-car sex had “directly caused, or directly contributed to cause” the STD transmission. The man was found liable. The woman was awarded $5.2 million to be paid by GEICO, which insured the man’s vehicle.

GEICO filed for the award to be overturned, alleging it had been denied due process and that the arbitration deal was unenforceable.

Court documents show that GEICO claimed the man’s policy covered only injuries that came “out of the ownership, maintenance or use of the ... auto” and that the woman’s “injuries arose from an intervening cause – namely, her failure to prevent transmission of STDs by having unprotected sex.”

The state appellate panel ruled that the lower court made no mistake in the case and upheld the decision.

The Kansas City Star reported that one of the judges concurred but said GEICO was offered “no meaningful opportunity to participate” in the lawsuit and existing law “relegat(es) the insurer to the status of a bystander.”

“This case presents novel and potentially important issues about whether an insurance carrier can be held liable under such policies for the consequences of two adults voluntarily having unprotected sex in the insured’s automobile,” noted U.S. Magistrate Judge Angel D. Mitchell in court documents. “Interpretation of these policies could have far-reaching implications for other policies with similar terms.”

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

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

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

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

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

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

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

People with HIV have an increased risk of breakthrough SARS-CoV-2 infections, a new study finds, and the authors say an additional primary vaccine dose should be considered for all who are living with the disease.

Currently, an additional primary dose administered 28 days after a second dose of the mRNA (Moderna or Pfizer) vaccines or after the first dose of the Johnson & Johnson (J&J) vaccine is recommended only for those with advanced or untreated HIV.

The Centers for Disease Control and Prevention recommends boosters for all adults with or without HIV.

Sally B. Coburn, PhD, of the department of epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, led the study, which was published online in JAMA Network Open. In their study, the researchers estimate the risk of breakthrough infections among fully vaccinated adults on the basis of HIV status in the United States.

Adults with HIV who were fully vaccinated before June 30, 2021, were matched with adults without HIV with regard to date of full vaccination, age, race/ethnicity, and sex. All were followed through Dec. 31, 2021.

Patients were considered fully vaccinated either 14 days after the second dose of the Pfizer or Moderna shots or 14 days after the single dose of the J&J shot.
 

Breakthrough risk 28% higher

In the study of 113,994 patients, researchers found that risk of breakthrough SARS-CoV-2 infection was low overall (3.8%) but was 28% higher among people with HIV in comparison with people without HIV (adjusted hazard ratio, 1.28; 95% confidence interval, 1.19-1.37).

The breakthrough rate was also higher in the HIV group (55 cases per 1,000 person-years, vs. 43 cases per 1,000 person-years in people without HIV).

Patients were drawn from the Corona-Infectious-Virus Epidemiology Team (CIVET)–II of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which is part of the International Epidemiology Databases to Evaluate AIDS (IeDEA) collaboration involving four cohorts.

Among people with HIV, those younger than 45 years (vs. those aged 45-54) and those with a history of COVID-19 were more likely to experience breakthrough infections. Those who did not get any additional shots after the primary vaccination were more likely to have breakthrough infections, amplifying the need to get boosters, the authors wrote.

There was no link between breakthrough infections and HIV viral load suppression, but high CD4 counts (> 500 cells/mm³) were associated with fewer breakthrough cases among people with HIV, they noted.

Monica Gandhi, MD, professor of medicine and associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, praised the study, noting that until now, large studies have not examined the rate of breakthrough infections among vaccinated people with HIV and people without HIV in the United States.

She told this news organization she agrees with the authors that a third dose for all who are living with HIV is needed because rates of breakthrough infections were high across all populations during the Omicron surge (which largely occurred after the period of this study).

She said she was not convinced the third shot was needed before Omicron, because breakthrough rates in both HIV and non-HIV groups were low.

“However, the most interesting part of this study for me was how well the vaccines worked in people with HIV with generally higher CD4 counts and virologic suppression, again telling us as HIV providers how well the HIV medicines work and how our patients with HIV have relatively normal immune systems if treated,” she said.

One limitation was that the study population was 92% male. Also, those without regular access to health care (who may be at greater risk for COVID-19) were less likely to be included in the study. People engaged in care may seek more frequent COVID-19 testing, which could lead to higher detection of breakthrough infections than in the general population.

“Future analyses should account for testing practices and include a larger proportion of women with HIV,” the authors wrote. “Ultimately, policy makers must determine the appropriate balance between preventing further COVID-19 infections and possibly unnecessary additional vaccinations.”

Coauthor Keri N. Althoff, PhD, told this news organization that there’s one unanswered question that would strengthen the call to action by the CDC: Do people with HIV have more severe postvaccination COVID-19 breakthrough illness?

“We have a second paper that is a preprint and currently under peer review,” she said. “In this paper, we found that people with HIV with a CD4 count less than 350 cells/mm³ were more likely to be hospitalized with postvaccination COVID-19 breakthrough illness compared to similar people without HIV. “

At a minimum, Dr. Althoff said, policymakers should consider including people with HIV with a CD4 less than 350 cells/mm³ (loosening the restriction to less than 200 cells/mm³) in their recommendations for people who are moderately or severely immunocompromised.

The research was funded with supplemental funds to the North American AIDS Cohort Collaboration on Research and Design. Dr. Coburn reports no relevant financial relationships. A coauthor has received grants from the Canadian Institutes of Health Research, Alberta Innovates, and University of Calgary/Alberta Health Services outside the submitted work. One coauthor reports serving as a consultant to Trio Health, Kennedy Dundas, and MedIQ outside the submitted work.

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

People with HIV have an increased risk of breakthrough SARS-CoV-2 infections, a new study finds, and the authors say an additional primary vaccine dose should be considered for all who are living with the disease.

Currently, an additional primary dose administered 28 days after a second dose of the mRNA (Moderna or Pfizer) vaccines or after the first dose of the Johnson & Johnson (J&J) vaccine is recommended only for those with advanced or untreated HIV.

The Centers for Disease Control and Prevention recommends boosters for all adults with or without HIV.

Sally B. Coburn, PhD, of the department of epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, led the study, which was published online in JAMA Network Open. In their study, the researchers estimate the risk of breakthrough infections among fully vaccinated adults on the basis of HIV status in the United States.

Adults with HIV who were fully vaccinated before June 30, 2021, were matched with adults without HIV with regard to date of full vaccination, age, race/ethnicity, and sex. All were followed through Dec. 31, 2021.

Patients were considered fully vaccinated either 14 days after the second dose of the Pfizer or Moderna shots or 14 days after the single dose of the J&J shot.
 

Breakthrough risk 28% higher

In the study of 113,994 patients, researchers found that risk of breakthrough SARS-CoV-2 infection was low overall (3.8%) but was 28% higher among people with HIV in comparison with people without HIV (adjusted hazard ratio, 1.28; 95% confidence interval, 1.19-1.37).

The breakthrough rate was also higher in the HIV group (55 cases per 1,000 person-years, vs. 43 cases per 1,000 person-years in people without HIV).

Patients were drawn from the Corona-Infectious-Virus Epidemiology Team (CIVET)–II of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which is part of the International Epidemiology Databases to Evaluate AIDS (IeDEA) collaboration involving four cohorts.

Among people with HIV, those younger than 45 years (vs. those aged 45-54) and those with a history of COVID-19 were more likely to experience breakthrough infections. Those who did not get any additional shots after the primary vaccination were more likely to have breakthrough infections, amplifying the need to get boosters, the authors wrote.

There was no link between breakthrough infections and HIV viral load suppression, but high CD4 counts (> 500 cells/mm³) were associated with fewer breakthrough cases among people with HIV, they noted.

Monica Gandhi, MD, professor of medicine and associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, praised the study, noting that until now, large studies have not examined the rate of breakthrough infections among vaccinated people with HIV and people without HIV in the United States.

She told this news organization she agrees with the authors that a third dose for all who are living with HIV is needed because rates of breakthrough infections were high across all populations during the Omicron surge (which largely occurred after the period of this study).

She said she was not convinced the third shot was needed before Omicron, because breakthrough rates in both HIV and non-HIV groups were low.

“However, the most interesting part of this study for me was how well the vaccines worked in people with HIV with generally higher CD4 counts and virologic suppression, again telling us as HIV providers how well the HIV medicines work and how our patients with HIV have relatively normal immune systems if treated,” she said.

One limitation was that the study population was 92% male. Also, those without regular access to health care (who may be at greater risk for COVID-19) were less likely to be included in the study. People engaged in care may seek more frequent COVID-19 testing, which could lead to higher detection of breakthrough infections than in the general population.

“Future analyses should account for testing practices and include a larger proportion of women with HIV,” the authors wrote. “Ultimately, policy makers must determine the appropriate balance between preventing further COVID-19 infections and possibly unnecessary additional vaccinations.”

Coauthor Keri N. Althoff, PhD, told this news organization that there’s one unanswered question that would strengthen the call to action by the CDC: Do people with HIV have more severe postvaccination COVID-19 breakthrough illness?

“We have a second paper that is a preprint and currently under peer review,” she said. “In this paper, we found that people with HIV with a CD4 count less than 350 cells/mm³ were more likely to be hospitalized with postvaccination COVID-19 breakthrough illness compared to similar people without HIV. “

At a minimum, Dr. Althoff said, policymakers should consider including people with HIV with a CD4 less than 350 cells/mm³ (loosening the restriction to less than 200 cells/mm³) in their recommendations for people who are moderately or severely immunocompromised.

The research was funded with supplemental funds to the North American AIDS Cohort Collaboration on Research and Design. Dr. Coburn reports no relevant financial relationships. A coauthor has received grants from the Canadian Institutes of Health Research, Alberta Innovates, and University of Calgary/Alberta Health Services outside the submitted work. One coauthor reports serving as a consultant to Trio Health, Kennedy Dundas, and MedIQ outside the submitted work.

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

People with HIV have an increased risk of breakthrough SARS-CoV-2 infections, a new study finds, and the authors say an additional primary vaccine dose should be considered for all who are living with the disease.

Currently, an additional primary dose administered 28 days after a second dose of the mRNA (Moderna or Pfizer) vaccines or after the first dose of the Johnson & Johnson (J&J) vaccine is recommended only for those with advanced or untreated HIV.

The Centers for Disease Control and Prevention recommends boosters for all adults with or without HIV.

Sally B. Coburn, PhD, of the department of epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, led the study, which was published online in JAMA Network Open. In their study, the researchers estimate the risk of breakthrough infections among fully vaccinated adults on the basis of HIV status in the United States.

Adults with HIV who were fully vaccinated before June 30, 2021, were matched with adults without HIV with regard to date of full vaccination, age, race/ethnicity, and sex. All were followed through Dec. 31, 2021.

Patients were considered fully vaccinated either 14 days after the second dose of the Pfizer or Moderna shots or 14 days after the single dose of the J&J shot.
 

Breakthrough risk 28% higher

In the study of 113,994 patients, researchers found that risk of breakthrough SARS-CoV-2 infection was low overall (3.8%) but was 28% higher among people with HIV in comparison with people without HIV (adjusted hazard ratio, 1.28; 95% confidence interval, 1.19-1.37).

The breakthrough rate was also higher in the HIV group (55 cases per 1,000 person-years, vs. 43 cases per 1,000 person-years in people without HIV).

Patients were drawn from the Corona-Infectious-Virus Epidemiology Team (CIVET)–II of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which is part of the International Epidemiology Databases to Evaluate AIDS (IeDEA) collaboration involving four cohorts.

Among people with HIV, those younger than 45 years (vs. those aged 45-54) and those with a history of COVID-19 were more likely to experience breakthrough infections. Those who did not get any additional shots after the primary vaccination were more likely to have breakthrough infections, amplifying the need to get boosters, the authors wrote.

There was no link between breakthrough infections and HIV viral load suppression, but high CD4 counts (> 500 cells/mm³) were associated with fewer breakthrough cases among people with HIV, they noted.

Monica Gandhi, MD, professor of medicine and associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, praised the study, noting that until now, large studies have not examined the rate of breakthrough infections among vaccinated people with HIV and people without HIV in the United States.

She told this news organization she agrees with the authors that a third dose for all who are living with HIV is needed because rates of breakthrough infections were high across all populations during the Omicron surge (which largely occurred after the period of this study).

She said she was not convinced the third shot was needed before Omicron, because breakthrough rates in both HIV and non-HIV groups were low.

“However, the most interesting part of this study for me was how well the vaccines worked in people with HIV with generally higher CD4 counts and virologic suppression, again telling us as HIV providers how well the HIV medicines work and how our patients with HIV have relatively normal immune systems if treated,” she said.

One limitation was that the study population was 92% male. Also, those without regular access to health care (who may be at greater risk for COVID-19) were less likely to be included in the study. People engaged in care may seek more frequent COVID-19 testing, which could lead to higher detection of breakthrough infections than in the general population.

“Future analyses should account for testing practices and include a larger proportion of women with HIV,” the authors wrote. “Ultimately, policy makers must determine the appropriate balance between preventing further COVID-19 infections and possibly unnecessary additional vaccinations.”

Coauthor Keri N. Althoff, PhD, told this news organization that there’s one unanswered question that would strengthen the call to action by the CDC: Do people with HIV have more severe postvaccination COVID-19 breakthrough illness?

“We have a second paper that is a preprint and currently under peer review,” she said. “In this paper, we found that people with HIV with a CD4 count less than 350 cells/mm³ were more likely to be hospitalized with postvaccination COVID-19 breakthrough illness compared to similar people without HIV. “

At a minimum, Dr. Althoff said, policymakers should consider including people with HIV with a CD4 less than 350 cells/mm³ (loosening the restriction to less than 200 cells/mm³) in their recommendations for people who are moderately or severely immunocompromised.

The research was funded with supplemental funds to the North American AIDS Cohort Collaboration on Research and Design. Dr. Coburn reports no relevant financial relationships. A coauthor has received grants from the Canadian Institutes of Health Research, Alberta Innovates, and University of Calgary/Alberta Health Services outside the submitted work. One coauthor reports serving as a consultant to Trio Health, Kennedy Dundas, and MedIQ outside the submitted work.

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

During the first year of the pandemic, profound changes in screen use and sleep timing occurred among U.S. adolescents as a result of spending more time using electronic devices, going to bed later, and getting up later, compared with before the pandemic, new research indicates.

The excessive screen time negatively affected sleep, said lead investigator Orsolya Kiss, PhD, with the Center for Health Sciences at SRI International, Menlo Park, Calif.

And what’s “concerning,” she told this news organization, is that there is no indication of any spontaneous decline in screen use in 2021, when there were fewer restrictions.

Dr. Kiss said she is “very much interested to see what future studies will show.”

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Sleep takes a pandemic hit

“Adolescents and families have turned to online activities and social platforms more than ever before to maintain wellbeing, [to] connect with friends and family, and for online schooling,” Dr. Kiss said in a conference statement.

She and her colleagues examined longitudinal data from 5,027 adolescents aged 11-14 years who are participating in the ongoing Adolescent Brain Cognitive Development (ABCD) study.

As part of the study, participants reported sleep and daily screen time use prior to and at six time points during the first year of the pandemic (May 2020 to March 2021).

During the first year of the pandemic, relative to before the pandemic, recreational screen time was dramatically higher, with adolescents spending about 45 minutes more on social media and 20 minutes more playing video games, Dr. Kiss reported.

The jump in screen time was coupled with changes in sleep patterns.

Adolescents’ wake up times were delayed about 1.5 hours during May and August 2020, relative to prepandemic levels. The delay was partly due to summer break; wake-up times returned to earlier times in the fall of 2020.

During all pandemic assessments, bedtimes were delayed by about 1 hour, even when the new school year started. This was particularly the case in older adolescents and girls.

The findings highlight the need to promote “balanced and informed use of social media platforms, video games, and other digital technology to ensure adequate opportunity to sleep and maintain other healthy behaviors during this critical period of developmental change,” the authors wrote in their conference abstract.
 

Mental illness risk

In an interview, Ruth Benca, MD, PhD, co-chair of the Alliance for Sleep, noted that “during adolescence, the tendency to become more of a night owl naturally worsens, and when kids have no sleep schedule imposed on them, these patterns become exacerbated.”

Dr. Benca, who was not involved in the study, also noted that altered sleep patterns are risk factors for psychiatric illness.

“Adolescence, in particular, is so critical for brain development, and it really raises the question of whether sleep disturbances in adolescence or poor sleep patterns are contributing to the increase psychiatric epidemic we’re seeing in adolescents and children these days,” said Dr. Benca, with Wake Forest University School of Medicine and Atrium Health Wake Forest Baptist, Winston-Salem, N.C.

Also weighing in on the study, journalist and author Lisa Lewis, MS, based in Southern California, said, “It’s not surprising that tech use and social media – which is such an important part of their social worlds – went up during the pandemic.”

Ms. Lewis, a parent of two teenagers, played a key role in California’s new healthy school start times law, the first of its kind in the nation, and is the author of the newly released book, The Sleep-Deprived Teen (Mango Publishing).

“Far too many adolescents aren’t getting anywhere close to the 8-10 hours of nightly sleep they need,” Ms. Lewis said in an interview.

She noted that the the American Academy of Pediatrics recommends no tech use an hour before bed.

“And there are other house rules parents can implement, such as charging all devices in a central location, like the kitchen. Making sleep a priority helps teens, but it helps parents too: No one functions well when they’re sleep-deprived,” Ms. Lewis added.

Support for the study was provided by the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Benca is a consultant for Idorsia Pharmaceuticals. Ms. Lewis has no relevant disclosures.

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

During the first year of the pandemic, profound changes in screen use and sleep timing occurred among U.S. adolescents as a result of spending more time using electronic devices, going to bed later, and getting up later, compared with before the pandemic, new research indicates.

The excessive screen time negatively affected sleep, said lead investigator Orsolya Kiss, PhD, with the Center for Health Sciences at SRI International, Menlo Park, Calif.

And what’s “concerning,” she told this news organization, is that there is no indication of any spontaneous decline in screen use in 2021, when there were fewer restrictions.

Dr. Kiss said she is “very much interested to see what future studies will show.”

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Sleep takes a pandemic hit

“Adolescents and families have turned to online activities and social platforms more than ever before to maintain wellbeing, [to] connect with friends and family, and for online schooling,” Dr. Kiss said in a conference statement.

She and her colleagues examined longitudinal data from 5,027 adolescents aged 11-14 years who are participating in the ongoing Adolescent Brain Cognitive Development (ABCD) study.

As part of the study, participants reported sleep and daily screen time use prior to and at six time points during the first year of the pandemic (May 2020 to March 2021).

During the first year of the pandemic, relative to before the pandemic, recreational screen time was dramatically higher, with adolescents spending about 45 minutes more on social media and 20 minutes more playing video games, Dr. Kiss reported.

The jump in screen time was coupled with changes in sleep patterns.

Adolescents’ wake up times were delayed about 1.5 hours during May and August 2020, relative to prepandemic levels. The delay was partly due to summer break; wake-up times returned to earlier times in the fall of 2020.

During all pandemic assessments, bedtimes were delayed by about 1 hour, even when the new school year started. This was particularly the case in older adolescents and girls.

The findings highlight the need to promote “balanced and informed use of social media platforms, video games, and other digital technology to ensure adequate opportunity to sleep and maintain other healthy behaviors during this critical period of developmental change,” the authors wrote in their conference abstract.
 

Mental illness risk

In an interview, Ruth Benca, MD, PhD, co-chair of the Alliance for Sleep, noted that “during adolescence, the tendency to become more of a night owl naturally worsens, and when kids have no sleep schedule imposed on them, these patterns become exacerbated.”

Dr. Benca, who was not involved in the study, also noted that altered sleep patterns are risk factors for psychiatric illness.

“Adolescence, in particular, is so critical for brain development, and it really raises the question of whether sleep disturbances in adolescence or poor sleep patterns are contributing to the increase psychiatric epidemic we’re seeing in adolescents and children these days,” said Dr. Benca, with Wake Forest University School of Medicine and Atrium Health Wake Forest Baptist, Winston-Salem, N.C.

Also weighing in on the study, journalist and author Lisa Lewis, MS, based in Southern California, said, “It’s not surprising that tech use and social media – which is such an important part of their social worlds – went up during the pandemic.”

Ms. Lewis, a parent of two teenagers, played a key role in California’s new healthy school start times law, the first of its kind in the nation, and is the author of the newly released book, The Sleep-Deprived Teen (Mango Publishing).

“Far too many adolescents aren’t getting anywhere close to the 8-10 hours of nightly sleep they need,” Ms. Lewis said in an interview.

She noted that the the American Academy of Pediatrics recommends no tech use an hour before bed.

“And there are other house rules parents can implement, such as charging all devices in a central location, like the kitchen. Making sleep a priority helps teens, but it helps parents too: No one functions well when they’re sleep-deprived,” Ms. Lewis added.

Support for the study was provided by the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Benca is a consultant for Idorsia Pharmaceuticals. Ms. Lewis has no relevant disclosures.

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

During the first year of the pandemic, profound changes in screen use and sleep timing occurred among U.S. adolescents as a result of spending more time using electronic devices, going to bed later, and getting up later, compared with before the pandemic, new research indicates.

The excessive screen time negatively affected sleep, said lead investigator Orsolya Kiss, PhD, with the Center for Health Sciences at SRI International, Menlo Park, Calif.

And what’s “concerning,” she told this news organization, is that there is no indication of any spontaneous decline in screen use in 2021, when there were fewer restrictions.

Dr. Kiss said she is “very much interested to see what future studies will show.”

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Sleep takes a pandemic hit

“Adolescents and families have turned to online activities and social platforms more than ever before to maintain wellbeing, [to] connect with friends and family, and for online schooling,” Dr. Kiss said in a conference statement.

She and her colleagues examined longitudinal data from 5,027 adolescents aged 11-14 years who are participating in the ongoing Adolescent Brain Cognitive Development (ABCD) study.

As part of the study, participants reported sleep and daily screen time use prior to and at six time points during the first year of the pandemic (May 2020 to March 2021).

During the first year of the pandemic, relative to before the pandemic, recreational screen time was dramatically higher, with adolescents spending about 45 minutes more on social media and 20 minutes more playing video games, Dr. Kiss reported.

The jump in screen time was coupled with changes in sleep patterns.

Adolescents’ wake up times were delayed about 1.5 hours during May and August 2020, relative to prepandemic levels. The delay was partly due to summer break; wake-up times returned to earlier times in the fall of 2020.

During all pandemic assessments, bedtimes were delayed by about 1 hour, even when the new school year started. This was particularly the case in older adolescents and girls.

The findings highlight the need to promote “balanced and informed use of social media platforms, video games, and other digital technology to ensure adequate opportunity to sleep and maintain other healthy behaviors during this critical period of developmental change,” the authors wrote in their conference abstract.
 

Mental illness risk

In an interview, Ruth Benca, MD, PhD, co-chair of the Alliance for Sleep, noted that “during adolescence, the tendency to become more of a night owl naturally worsens, and when kids have no sleep schedule imposed on them, these patterns become exacerbated.”

Dr. Benca, who was not involved in the study, also noted that altered sleep patterns are risk factors for psychiatric illness.

“Adolescence, in particular, is so critical for brain development, and it really raises the question of whether sleep disturbances in adolescence or poor sleep patterns are contributing to the increase psychiatric epidemic we’re seeing in adolescents and children these days,” said Dr. Benca, with Wake Forest University School of Medicine and Atrium Health Wake Forest Baptist, Winston-Salem, N.C.

Also weighing in on the study, journalist and author Lisa Lewis, MS, based in Southern California, said, “It’s not surprising that tech use and social media – which is such an important part of their social worlds – went up during the pandemic.”

Ms. Lewis, a parent of two teenagers, played a key role in California’s new healthy school start times law, the first of its kind in the nation, and is the author of the newly released book, The Sleep-Deprived Teen (Mango Publishing).

“Far too many adolescents aren’t getting anywhere close to the 8-10 hours of nightly sleep they need,” Ms. Lewis said in an interview.

She noted that the the American Academy of Pediatrics recommends no tech use an hour before bed.

“And there are other house rules parents can implement, such as charging all devices in a central location, like the kitchen. Making sleep a priority helps teens, but it helps parents too: No one functions well when they’re sleep-deprived,” Ms. Lewis added.

Support for the study was provided by the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Benca is a consultant for Idorsia Pharmaceuticals. Ms. Lewis has no relevant disclosures.

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

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.

A person’s ‘genetic’ height – the height they are predicted to reach independent of environmental influences – may be an underappreciated risk factor for a wide range of chronic conditions, according to a study published in PLOS Genetics.

Prior studies have investigated height as a risk factor for chronic diseases, such as a higher risk for atrial fibrillation and a reduced risk of cardiovascular disease. It’s been consistently difficult, however, to eliminate the confounding influences of diet, socioeconomics, lifestyle behaviors, and other environmental factors that may interfere with a person’s reaching their expected height based on their genes.

This study, however, was able to better parse those differences by using Mendelian randomization within the comprehensive clinical and genetic dataset of a national health care system biobank. Mendelian randomization uses “genetic instruments for exposures of interest under the assumption that genotype is less susceptible to confounding than measured exposures,” the authors explained. The findings confirmed previously suspected associations between height and a range of cardiovascular and metabolic conditions as well as revealing new associations with several other conditions.
 

Prior associations confirmed, new associations uncovered

The results confirmed that being tall is linked to a higher risk of atrial fibrillation and varicose veins, and a lower risk of coronary heart disease, high blood pressure, and high cholesterol. The study also uncovered new associations between greater height and a higher risk of peripheral neuropathy, which is caused by damage to nerves on the extremities, as well as skin and bone infections, such as leg and foot ulcers.

The meta-analysis “identified five additional traits associated with genetically-predicted height,” wrote Sridharan Raghavan, MD, assistant professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues. “Two were genitourinary conditions – erectile dysfunction and urinary retention – that can be associated with neuropathy, and a third was a phecode for nonspecific skin disorders that may be related to skin infections – consistent with the race/ethnicity stratified results.”
 

Removing potential confounders

F. Perry Wilson, MD, associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study, said the findings were not particularly surprising overall, but it’s striking that the researchers had ”such a large cohort with such detailed electronic health records allowing for the comparison of genetic height with a variety of clinical outcomes.” He also noted the study’s strength in using Mendelian randomization so that the exposure is the predicted genetic height instead of a person’s measured height.

“This is key, since lots of things affect actual height – nutrition is an important one that could certainly be linked to disease as well,” Dr. Wilson said. ”By using genetic height, the authors remove these potential confounders. Since genetic height is “assigned” at birth (or conception), there is little opportunity for confounding. Of course, it is possible that some of the gene variants used to predict genetic height actually do something else, such as make you seek out less nutritious meals, but by and large this is how these types of studies need to be done.”
 

Height may impact over 100 clinical traits

The study relied on data from the U.S. Veteran Affairs Million Veteran Program with 222,300 non-Hispanic White and 58,151 non-Hispanic Black participants. The researchers first estimated the likelihood of participants’ genetic height based on 3,290 genetic variants determined to affect genetic height in a recent European-ancestry genome-wide meta-analysis. Then they compared these estimates with participants’ actual height in the VA medical record, adjusting for age, sex, and other genetic characteristics.

In doing so, the researchers found 345 clinical traits that were associated with the actual measured height in White participants plus another 17 clinical trials linked to actual measured height in Black participants. An overall 127 of these clinical traits were significantly associated with White participants’ genetically predicted height, and two of them were significantly associated with Black participants’ genetically predicted height.

In analyzing all these data together, the researchers were largely able to separate out those associations between genetically predicted height and certain health conditions from those associations between health conditions and a person’s actual measured height. They also determined that including body mass index as a covariate had little impact on the results. The researchers conducted the appropriate statistical correction to ensure the use of so many variables did not result in spurious statistical significance in some associations.

“Using genetic methods applied to the VA Million Veteran Program, we found evidence that adult height may impact over 100 clinical traits, including several conditions associated with poor outcomes and quality of life – peripheral neuropathy, lower extremity ulcers, and chronic venous insufficiency. We conclude that height may be an unrecognized nonmodifiable risk factor for several common conditions in adults.”
 

Height linked with health conditions

Genetically predicted height predicted a reduced risk of hyperlipidemia and hypertension independent of coronary heart disease, the analysis revealed. Genetically predicted height was also linked to an approximately 51% increased risk of atrial fibrillation in participants without coronary heart disease but, paradoxically, only a 39% increased risk in those with coronary heart disease, despite coronary heart disease being a risk factor for atrial fibrillation. Genetically predicted height was also associated with a greater risk of varicose veins in the legs and deep vein thrombosis.

Another novel association uncovered by the analysis was between women’s genetically predicted height and both asthma and nonspecific peripheral nerve disorders. “Whether these associations reflect differences by sex in disease pathophysiology related to height may warrant exploration in a sample with better balance between men and women,” the authors wrote. “In sum, our results suggest that an individual’s height may warrant consideration as a nonmodifiable predictor for several common conditions, particularly those affecting peripheral/distal extremities that are most physically impacted by tall stature.”

A substantial limitation of the study was its homogeneity of participants, who were 92% male with an average height of 176 cm and an average BMI of 30.1. The Black participants tended to be younger, with an average age of 58 compared with 64 years in the White participants, but the groups were otherwise similar in height and weight.* The database included data from Hispanic participants, but the researchers excluded these data because of the small sample size.

The smaller dataset for Black participants was a limitation as well as the fact that the genome-wide association study the researchers relied on came from a European population, which may not be as accurate in people with other ancestry, Dr. Wilson said. The bigger limitation, however, is what the findings’ clinical relevance is.
 

What does it all mean?

“Genetic height is in your genes – there is nothing to be done about it – so it is more of academic interest than clinical interest,” Dr. Wilson said. It’s not even clear whether incorporating a person’s height – actual or genetically predicted, if it could be easily determined for each person – into risk calculators. ”To know whether it would be beneficial to use height (or genetic height) as a risk factor, you’d need to examine each condition of interest, adjusting for all known risk factors, to see if height improved the prediction,” Dr. Wilson said. “I suspect for most conditions, the well-known risk factors would swamp height. For example, high genetic height might truly increase risk for neuropathy. But diabetes might increase the risk so much more that height is not particularly relevant.”

On the other hand, the fact that height in general has any potential influence at all on disease risk may inspire physicians to consider other risk factors in especially tall individuals.

”Physicians may find it interesting that we have some confirmation that height does increase the risk of certain conditions,” Dr. Wilson said. “While this is unlikely to dramatically change practice, they may be a bit more diligent in looking for other relevant risk factors for the diseases found in this study in their very tall patients.”

The research was funded by the U.S. Department of Veteran Affairs, the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the National Institutes of Health, and a Linda Pechenik Montague Investigator award. One study coauthor is a full-time employee of Novartis Institutes of Biomedical Research. The other authors and Dr. Wilson had no disclosures.

*Correction, 6/29/22: An earlier version of this article misstated the average age of Black participants.