Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.

They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.

Spare me.

I’m not looking for any of that. In fact, I really don’t care.

Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.

It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.

People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.

I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.

It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise. After 23 years the only gratitude that means anything to me is the occasional heartfelt “thank you” from a patient.

And that’s all I need.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.

They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.

Spare me.

I’m not looking for any of that. In fact, I really don’t care.

Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.

It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.

People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.

I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.

It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise. After 23 years the only gratitude that means anything to me is the occasional heartfelt “thank you” from a patient.

And that’s all I need.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.

They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.

Spare me.

I’m not looking for any of that. In fact, I really don’t care.

Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.

It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.

People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.

I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.

It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise. After 23 years the only gratitude that means anything to me is the occasional heartfelt “thank you” from a patient.

And that’s all I need.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Overwhelming numbers of early puberty cases among girls have been reported during the pandemic, according a report copublished by the Washington Post and The Fuller Project.

Early puberty is uncommon, affecting about 1 in every 5,000 to 10,000 children, with cases about 10 times higher in girls than boys. But since the pandemic started, doctors and parents around the world have noted a substantial surge in early puberty.

In some cases, girls as young as 5 have begun developing breasts and girls younger than 8 have started menstruation.

“I noticed that quite a few of my [girl patients] got their period after a lockdown,” Adiaha Spinks-Franklin, MD, a pediatrician at Texas Children’s Hospital, Houston, told the news outlets.

The condition, also called precocious puberty, is defined as puberty-related changes earlier than normal or expected, which starts around age 8 for girls and age 9 for boys. It can sometimes be caused by genetic syndromes, central nervous system issues, or tumors on the ovaries, adrenal glands, pituitary gland, or brain.

Pediatricians across the world have reported more precocious puberty cases, the news outlets reported, including in the United States, India, Italy, and Turkey.

A recent study found that more than 300 girls were referred to five pediatric endocrinology centers in Italy between March and September 2020, as opposed to 140 referrals during the same time period in 2019.

In another study, a Turkish pediatric endocrinology clinic reported 58 cases during the first year of the pandemic, as compared with 66 total cases during the 3 previous years.

Early puberty tends to mean there are other mental and physical issues, though in most cases, an exact cause can’t be found. Doctors have tied the current uptick to the stress of the pandemic and lockdowns, including reduced physical activity and increased consumption of unhealthy food, which are things linked to a higher risk of early puberty.

“I think it’s directly related to the amount of stress that the children have gone through,” Vaishakhi Rustagi, MD, a pediatric endocrinologist in Delhi, India, told the news outlets.

In a typical year, Dr. Rustagi sees about 20 patients with early puberty. Since mid-2020, she’s seen more than 300 girls with the condition. Imaging scans and ultrasounds haven’t found tumors, and the cause has been mostly unidentifiable, though Dr. Rustagi attributed it to stress and grief.

“These children have lost family members,” she said.

Early puberty is known to increase depression, eating disorders, substance abuse, and antisocial behavior, the news outlets reported.

The main treatment for the condition, a form of hormone therapy known as gonadotropin-releasing hormone analogue therapy, is known to work very well. But some patients and families may not seek treatment because of a lack of awareness or stigmas that come with menstruation.

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

Overwhelming numbers of early puberty cases among girls have been reported during the pandemic, according a report copublished by the Washington Post and The Fuller Project.

Early puberty is uncommon, affecting about 1 in every 5,000 to 10,000 children, with cases about 10 times higher in girls than boys. But since the pandemic started, doctors and parents around the world have noted a substantial surge in early puberty.

In some cases, girls as young as 5 have begun developing breasts and girls younger than 8 have started menstruation.

“I noticed that quite a few of my [girl patients] got their period after a lockdown,” Adiaha Spinks-Franklin, MD, a pediatrician at Texas Children’s Hospital, Houston, told the news outlets.

The condition, also called precocious puberty, is defined as puberty-related changes earlier than normal or expected, which starts around age 8 for girls and age 9 for boys. It can sometimes be caused by genetic syndromes, central nervous system issues, or tumors on the ovaries, adrenal glands, pituitary gland, or brain.

Pediatricians across the world have reported more precocious puberty cases, the news outlets reported, including in the United States, India, Italy, and Turkey.

A recent study found that more than 300 girls were referred to five pediatric endocrinology centers in Italy between March and September 2020, as opposed to 140 referrals during the same time period in 2019.

In another study, a Turkish pediatric endocrinology clinic reported 58 cases during the first year of the pandemic, as compared with 66 total cases during the 3 previous years.

Early puberty tends to mean there are other mental and physical issues, though in most cases, an exact cause can’t be found. Doctors have tied the current uptick to the stress of the pandemic and lockdowns, including reduced physical activity and increased consumption of unhealthy food, which are things linked to a higher risk of early puberty.

“I think it’s directly related to the amount of stress that the children have gone through,” Vaishakhi Rustagi, MD, a pediatric endocrinologist in Delhi, India, told the news outlets.

In a typical year, Dr. Rustagi sees about 20 patients with early puberty. Since mid-2020, she’s seen more than 300 girls with the condition. Imaging scans and ultrasounds haven’t found tumors, and the cause has been mostly unidentifiable, though Dr. Rustagi attributed it to stress and grief.

“These children have lost family members,” she said.

Early puberty is known to increase depression, eating disorders, substance abuse, and antisocial behavior, the news outlets reported.

The main treatment for the condition, a form of hormone therapy known as gonadotropin-releasing hormone analogue therapy, is known to work very well. But some patients and families may not seek treatment because of a lack of awareness or stigmas that come with menstruation.

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

Overwhelming numbers of early puberty cases among girls have been reported during the pandemic, according a report copublished by the Washington Post and The Fuller Project.

Early puberty is uncommon, affecting about 1 in every 5,000 to 10,000 children, with cases about 10 times higher in girls than boys. But since the pandemic started, doctors and parents around the world have noted a substantial surge in early puberty.

In some cases, girls as young as 5 have begun developing breasts and girls younger than 8 have started menstruation.

“I noticed that quite a few of my [girl patients] got their period after a lockdown,” Adiaha Spinks-Franklin, MD, a pediatrician at Texas Children’s Hospital, Houston, told the news outlets.

The condition, also called precocious puberty, is defined as puberty-related changes earlier than normal or expected, which starts around age 8 for girls and age 9 for boys. It can sometimes be caused by genetic syndromes, central nervous system issues, or tumors on the ovaries, adrenal glands, pituitary gland, or brain.

Pediatricians across the world have reported more precocious puberty cases, the news outlets reported, including in the United States, India, Italy, and Turkey.

A recent study found that more than 300 girls were referred to five pediatric endocrinology centers in Italy between March and September 2020, as opposed to 140 referrals during the same time period in 2019.

In another study, a Turkish pediatric endocrinology clinic reported 58 cases during the first year of the pandemic, as compared with 66 total cases during the 3 previous years.

Early puberty tends to mean there are other mental and physical issues, though in most cases, an exact cause can’t be found. Doctors have tied the current uptick to the stress of the pandemic and lockdowns, including reduced physical activity and increased consumption of unhealthy food, which are things linked to a higher risk of early puberty.

“I think it’s directly related to the amount of stress that the children have gone through,” Vaishakhi Rustagi, MD, a pediatric endocrinologist in Delhi, India, told the news outlets.

In a typical year, Dr. Rustagi sees about 20 patients with early puberty. Since mid-2020, she’s seen more than 300 girls with the condition. Imaging scans and ultrasounds haven’t found tumors, and the cause has been mostly unidentifiable, though Dr. Rustagi attributed it to stress and grief.

“These children have lost family members,” she said.

Early puberty is known to increase depression, eating disorders, substance abuse, and antisocial behavior, the news outlets reported.

The main treatment for the condition, a form of hormone therapy known as gonadotropin-releasing hormone analogue therapy, is known to work very well. But some patients and families may not seek treatment because of a lack of awareness or stigmas that come with menstruation.

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

The Centers for Disease Control and Prevention has recommended that all adults aged 19-59 years receive a vaccination for hepatitis B.

It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.

The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.

The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.

Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.

Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.

Hepatitis B infection rates are particularly elevated among African Americans.

Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.

In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.

CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.

The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.

The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.

People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.

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

The Centers for Disease Control and Prevention has recommended that all adults aged 19-59 years receive a vaccination for hepatitis B.

It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.

The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.

The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.

Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.

Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.

Hepatitis B infection rates are particularly elevated among African Americans.

Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.

In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.

CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.

The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.

The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.

People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.

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

The Centers for Disease Control and Prevention has recommended that all adults aged 19-59 years receive a vaccination for hepatitis B.

It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.

The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.

The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.

Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.

Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.

Hepatitis B infection rates are particularly elevated among African Americans.

Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.

In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.

CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.

The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.

The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.

People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.

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

Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.

The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.

The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.

While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.

“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.

In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.

“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”

Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.

“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.

Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.

Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.

The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.

The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.

While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.

“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.

In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.

“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”

Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.

“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.

Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.

Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.

The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.

The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.

While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.

“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.

In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.

“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”

Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.

“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.

Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.

A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in Nature Medicine.

Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.

“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” Christopher Chiu, MD, PhD, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.

Starting in March 2021, Dr. Chiu and colleagues carefully selected 36 volunteers aged 18-30 years who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.

The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.

As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for 2 weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.

Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose, and sore throat. Some also had headaches, muscle and joint pain, fatigue, and fever.

About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.

The research team reported several other findings:

• Small amounts of the virus can make someone sick. About 10 mcm, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.
• About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.
• It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.
• COVID-19 has a short incubation period. It takes about 2 days after infection for someone to begin shedding the virus to others.
• People become contagious and shed high amounts of the virus before they show symptoms.
• In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.
• The study volunteers shed the virus for about 6 days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.
• Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70%-80% of the viable virus had been generated.

The findings emphasized the importance of contagious people covering their mouth and nose when sick to protect others, Dr. Chiu told CNN.

None of the study volunteers developed lung issues as part of their infection, CNN reported. Dr. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.

Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Dr. Chiu told CNN.

Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.

“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Dr. Chiu said in a statement.

The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Dr. Chiu told CNN, despite receiving the same dose of the virus as those who got sick.

Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.

“There are lots of other things that help protect us,” Dr. Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems ... and we’re really interested in trying to understand what those are.”

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

A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in Nature Medicine.

Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.

“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” Christopher Chiu, MD, PhD, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.

Starting in March 2021, Dr. Chiu and colleagues carefully selected 36 volunteers aged 18-30 years who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.

The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.

As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for 2 weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.

Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose, and sore throat. Some also had headaches, muscle and joint pain, fatigue, and fever.

About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.

The research team reported several other findings:

• Small amounts of the virus can make someone sick. About 10 mcm, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.
• About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.
• It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.
• COVID-19 has a short incubation period. It takes about 2 days after infection for someone to begin shedding the virus to others.
• People become contagious and shed high amounts of the virus before they show symptoms.
• In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.
• The study volunteers shed the virus for about 6 days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.
• Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70%-80% of the viable virus had been generated.

The findings emphasized the importance of contagious people covering their mouth and nose when sick to protect others, Dr. Chiu told CNN.

None of the study volunteers developed lung issues as part of their infection, CNN reported. Dr. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.

Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Dr. Chiu told CNN.

Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.

“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Dr. Chiu said in a statement.

The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Dr. Chiu told CNN, despite receiving the same dose of the virus as those who got sick.

Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.

“There are lots of other things that help protect us,” Dr. Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems ... and we’re really interested in trying to understand what those are.”

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

A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in Nature Medicine.

Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.

“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” Christopher Chiu, MD, PhD, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.

Starting in March 2021, Dr. Chiu and colleagues carefully selected 36 volunteers aged 18-30 years who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.

The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.

As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for 2 weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.

Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose, and sore throat. Some also had headaches, muscle and joint pain, fatigue, and fever.

About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.

The research team reported several other findings:

• Small amounts of the virus can make someone sick. About 10 mcm, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.
• About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.
• It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.
• COVID-19 has a short incubation period. It takes about 2 days after infection for someone to begin shedding the virus to others.
• People become contagious and shed high amounts of the virus before they show symptoms.
• In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.
• The study volunteers shed the virus for about 6 days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.
• Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70%-80% of the viable virus had been generated.

The findings emphasized the importance of contagious people covering their mouth and nose when sick to protect others, Dr. Chiu told CNN.

None of the study volunteers developed lung issues as part of their infection, CNN reported. Dr. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.

Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Dr. Chiu told CNN.

Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.

“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Dr. Chiu said in a statement.

The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Dr. Chiu told CNN, despite receiving the same dose of the virus as those who got sick.

Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.

“There are lots of other things that help protect us,” Dr. Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems ... and we’re really interested in trying to understand what those are.”

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

U.S. hospitals are being warned to prepare for a potential cyberattack from either the Russian government, criminal gangs resident in Russia, or both, as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.

The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.

CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.

John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”

He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
 

Criminal gangs remain a threat

Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”

On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”

Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.

However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.

The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
 

Hospitals better prepared, but still have gaps

Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.

The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”

According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.

That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.

The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:

• Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
• Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
• Check the redundancy, resiliency, and security of the organization’s network and data backups;
• Document, update, and practice the organization’s incident response plan.

Hospitals increasingly targeted

In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.

The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.

“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.

In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
 

Physician practices also at risk

Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.

Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.

“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
 

Hackers can hit service suppliers

Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.

Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”

More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.

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

U.S. hospitals are being warned to prepare for a potential cyberattack from either the Russian government, criminal gangs resident in Russia, or both, as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.

The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.

CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.

John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”

He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
 

Criminal gangs remain a threat

Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”

On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”

Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.

However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.

The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
 

Hospitals better prepared, but still have gaps

Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.

The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”

According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.

That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.

The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:

• Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
• Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
• Check the redundancy, resiliency, and security of the organization’s network and data backups;
• Document, update, and practice the organization’s incident response plan.

Hospitals increasingly targeted

In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.

The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.

“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.

In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
 

Physician practices also at risk

Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.

Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.

“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
 

Hackers can hit service suppliers

Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.

Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”

More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.

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

U.S. hospitals are being warned to prepare for a potential cyberattack from either the Russian government, criminal gangs resident in Russia, or both, as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.

The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.

CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.

John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”

He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
 

Criminal gangs remain a threat

Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”

On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”

Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.

However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.

The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
 

Hospitals better prepared, but still have gaps

Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.

The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”

According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.

That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.

The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:

• Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
• Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
• Check the redundancy, resiliency, and security of the organization’s network and data backups;
• Document, update, and practice the organization’s incident response plan.

Hospitals increasingly targeted

In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.

The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.

“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.

In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
 

Physician practices also at risk

Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.

Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.

“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
 

Hackers can hit service suppliers

Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.

Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”

More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.

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

Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4 receptor alpha subunit. It has been approved in the United States for the treatment of adults with moderate-to-severe AD since 2017 and has since been approved for children and adolescents older than 6 years. Many real-world studies of the effectiveness of dupilumab have been published over the past few years. Kojanova and colleagues reported findings from a retrospective, multicenter study of 360 adults with severe AD who received dupilumab. They found that a high proportion of patients achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16 (66.6%), 1 year (89.5%), and 2 years (95.8%). Drug persistence rates were very high (> 90%) throughout the 2 years of therapy, suggesting that dupilumab was effective and well-tolerated.

Dupilumab was previously found to be associated with increased conjunctivitis in clinical trials and real-world studies. Schneeweiss and colleagues conducted a population-based longitudinal study of 5,004,117 patients with AD who newly initiated dupilumab, methotrexate, mycophenolate, and cyclosporine. They found that the risk of developing conjunctivitis diagnosed in clinical practice within 6 months of treatment initiation was approximately double with dupilumab compared with methotrexate, mycophenolate, or cyclosporine. Interestingly, comorbid asthma was found to be a risk factor for conjunctivitis in dupilumab initiators. This study provides insight into how commonly clinically significant conjunctivitis occurs with dupilumab treatment. Of note, the study results may underestimate the incidence of conjunctivitis because milder cases may go undetected.

Upadacitinib is an oral selective Janus kinase (JAK) 1 inhibitor that was approved in the United States in 2022 for the treatment of moderate-to-severe AD. Simpson and colleagues reported on the long-term efficacy and safety of oral upadacitinib from the phase 3 double-blind, randomized controlled trials Measure Up 1 and Measure Up 2 in adolescents and adults with moderate-to-severe atopic dermatitis ho had an inadequate response to topical therapy. The initial phase of the Measure Up 1 and Measure Up 2 studies was 16 weeks in duration, with a placebo control group. At week 16, patients who received 15 or 30 mg upadacitinib in the initial 16 weeks of the study continued to receive that dose. Patients who received placebo in the initial 16 weeks were randomly assigned to receive oral 15 mg or 30 mg upadacitinib daily. So, in the long run, all patients received upadacitinib in the second phase of the study but were blinded to the dose they were receiving. The results from the first 16 weeks of treatment were previously published. Simpson and colleagues reported on the results up to week 52 from the second phase of the study. They showed that at week 52, 82.0% and 79.1% of patients in Measure Up 1 and Measure Up 2 achieved a 75% improvement in EASI-75 when continuing on 15 mg upadacitinib and 84.9% and 84.3% in patients continuing 30 mg upadacitinib, respectively. More than 80% of patients who switched from placebo to upadacitinib at week 16 achieved EASI-75 at week 52. No safety signals were observed in this phase of the study that were not previously observed in other studies of upadacitinib for atopic dermatitis and other indications (rheumatoid arthritis and psoriatic arthritis). These results indicate that upadacitinib has durable efficacy with long-term treatment in moderate-to-severe AD. These studies are ongoing, and I look forward to future results reporting for even longer-term treatment.

It is an exciting time in dermatology with the arrival of multiple novel therapies for atopic dermatitis. The field has already benefited so much by the tremendous interest and research effort into understanding how to best manage this disease. With so many more treatments in the pipeline, perhaps the best is yet to come.

Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4 receptor alpha subunit. It has been approved in the United States for the treatment of adults with moderate-to-severe AD since 2017 and has since been approved for children and adolescents older than 6 years. Many real-world studies of the effectiveness of dupilumab have been published over the past few years. Kojanova and colleagues reported findings from a retrospective, multicenter study of 360 adults with severe AD who received dupilumab. They found that a high proportion of patients achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16 (66.6%), 1 year (89.5%), and 2 years (95.8%). Drug persistence rates were very high (> 90%) throughout the 2 years of therapy, suggesting that dupilumab was effective and well-tolerated.

Dupilumab was previously found to be associated with increased conjunctivitis in clinical trials and real-world studies. Schneeweiss and colleagues conducted a population-based longitudinal study of 5,004,117 patients with AD who newly initiated dupilumab, methotrexate, mycophenolate, and cyclosporine. They found that the risk of developing conjunctivitis diagnosed in clinical practice within 6 months of treatment initiation was approximately double with dupilumab compared with methotrexate, mycophenolate, or cyclosporine. Interestingly, comorbid asthma was found to be a risk factor for conjunctivitis in dupilumab initiators. This study provides insight into how commonly clinically significant conjunctivitis occurs with dupilumab treatment. Of note, the study results may underestimate the incidence of conjunctivitis because milder cases may go undetected.

Upadacitinib is an oral selective Janus kinase (JAK) 1 inhibitor that was approved in the United States in 2022 for the treatment of moderate-to-severe AD. Simpson and colleagues reported on the long-term efficacy and safety of oral upadacitinib from the phase 3 double-blind, randomized controlled trials Measure Up 1 and Measure Up 2 in adolescents and adults with moderate-to-severe atopic dermatitis ho had an inadequate response to topical therapy. The initial phase of the Measure Up 1 and Measure Up 2 studies was 16 weeks in duration, with a placebo control group. At week 16, patients who received 15 or 30 mg upadacitinib in the initial 16 weeks of the study continued to receive that dose. Patients who received placebo in the initial 16 weeks were randomly assigned to receive oral 15 mg or 30 mg upadacitinib daily. So, in the long run, all patients received upadacitinib in the second phase of the study but were blinded to the dose they were receiving. The results from the first 16 weeks of treatment were previously published. Simpson and colleagues reported on the results up to week 52 from the second phase of the study. They showed that at week 52, 82.0% and 79.1% of patients in Measure Up 1 and Measure Up 2 achieved a 75% improvement in EASI-75 when continuing on 15 mg upadacitinib and 84.9% and 84.3% in patients continuing 30 mg upadacitinib, respectively. More than 80% of patients who switched from placebo to upadacitinib at week 16 achieved EASI-75 at week 52. No safety signals were observed in this phase of the study that were not previously observed in other studies of upadacitinib for atopic dermatitis and other indications (rheumatoid arthritis and psoriatic arthritis). These results indicate that upadacitinib has durable efficacy with long-term treatment in moderate-to-severe AD. These studies are ongoing, and I look forward to future results reporting for even longer-term treatment.

It is an exciting time in dermatology with the arrival of multiple novel therapies for atopic dermatitis. The field has already benefited so much by the tremendous interest and research effort into understanding how to best manage this disease. With so many more treatments in the pipeline, perhaps the best is yet to come.

Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4 receptor alpha subunit. It has been approved in the United States for the treatment of adults with moderate-to-severe AD since 2017 and has since been approved for children and adolescents older than 6 years. Many real-world studies of the effectiveness of dupilumab have been published over the past few years. Kojanova and colleagues reported findings from a retrospective, multicenter study of 360 adults with severe AD who received dupilumab. They found that a high proportion of patients achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16 (66.6%), 1 year (89.5%), and 2 years (95.8%). Drug persistence rates were very high (> 90%) throughout the 2 years of therapy, suggesting that dupilumab was effective and well-tolerated.

Dupilumab was previously found to be associated with increased conjunctivitis in clinical trials and real-world studies. Schneeweiss and colleagues conducted a population-based longitudinal study of 5,004,117 patients with AD who newly initiated dupilumab, methotrexate, mycophenolate, and cyclosporine. They found that the risk of developing conjunctivitis diagnosed in clinical practice within 6 months of treatment initiation was approximately double with dupilumab compared with methotrexate, mycophenolate, or cyclosporine. Interestingly, comorbid asthma was found to be a risk factor for conjunctivitis in dupilumab initiators. This study provides insight into how commonly clinically significant conjunctivitis occurs with dupilumab treatment. Of note, the study results may underestimate the incidence of conjunctivitis because milder cases may go undetected.

Upadacitinib is an oral selective Janus kinase (JAK) 1 inhibitor that was approved in the United States in 2022 for the treatment of moderate-to-severe AD. Simpson and colleagues reported on the long-term efficacy and safety of oral upadacitinib from the phase 3 double-blind, randomized controlled trials Measure Up 1 and Measure Up 2 in adolescents and adults with moderate-to-severe atopic dermatitis ho had an inadequate response to topical therapy. The initial phase of the Measure Up 1 and Measure Up 2 studies was 16 weeks in duration, with a placebo control group. At week 16, patients who received 15 or 30 mg upadacitinib in the initial 16 weeks of the study continued to receive that dose. Patients who received placebo in the initial 16 weeks were randomly assigned to receive oral 15 mg or 30 mg upadacitinib daily. So, in the long run, all patients received upadacitinib in the second phase of the study but were blinded to the dose they were receiving. The results from the first 16 weeks of treatment were previously published. Simpson and colleagues reported on the results up to week 52 from the second phase of the study. They showed that at week 52, 82.0% and 79.1% of patients in Measure Up 1 and Measure Up 2 achieved a 75% improvement in EASI-75 when continuing on 15 mg upadacitinib and 84.9% and 84.3% in patients continuing 30 mg upadacitinib, respectively. More than 80% of patients who switched from placebo to upadacitinib at week 16 achieved EASI-75 at week 52. No safety signals were observed in this phase of the study that were not previously observed in other studies of upadacitinib for atopic dermatitis and other indications (rheumatoid arthritis and psoriatic arthritis). These results indicate that upadacitinib has durable efficacy with long-term treatment in moderate-to-severe AD. These studies are ongoing, and I look forward to future results reporting for even longer-term treatment.

It is an exciting time in dermatology with the arrival of multiple novel therapies for atopic dermatitis. The field has already benefited so much by the tremendous interest and research effort into understanding how to best manage this disease. With so many more treatments in the pipeline, perhaps the best is yet to come.

SEATTLE – The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene.

LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.

The study protocol called for injection of the therapy into one eye and a placebo into the other, using the patient as his or own placebo control. The results in the treated eye were encouraging, though modest. “This is not hitting it out of the ballpark. But for people whose vision is devastated by this disease, it certainly is a first step,” said Nancy J. Newman, MD, during a press conference held March 29 in advance of the 2022 annual meeting of the American Academy of Neurology.

Dr. Newman also noted a surprise finding: Visual improvement also occurred in the placebo-control eye. This was noted in previous studies, called RESCUE and REVERSE, and follow-up studies in monkeys found viral vector in the unaffected eye 3-6 months after an injection. “This would imply some kind of transport within retrograde up the opposite optic nerve after crossing in the chiasm to the eye, but this is going to take a fair bit of work to know exactly how that happens,” said Dr. Newman

Unfortunately, the phase 3 REFLECT study was designed before that process was understood. “This was not a case-control study by person, it was by eye. And that was a mistake, because it turns out there is a does appear to be second eye effects. We do not have naive controls here that did not receive any injection at all in any eye. That’s something that we will [do going] forward,” said Dr. Newman.

Despite the problem with placebo, the results were encouraging. “Those patients who had both eyes injected with the drug did better than in those who had one eye injected with drug and one eye injected with placebo, suggesting some sort of dose effect. There were no adverse events other than what we would expect from injecting [into] eyes. Those treated with the drug had more ocular inflammation, as would also be expected, but all were easily treated with topical medications,” said Dr. Newman.
 

What are the long-term effects?

Natalia Rost, MD, who chairs the AAN Science Committee, commented after the presentation: “We’re quite impressed with advances in gene therapy. The question is, are there early indications that this improvement in vision will have a lasting effect?”

Dr. Newman responded that ongoing data from earlier studies are also encouraging regarding the long-term effect of the treatment. At 4 years, there was a difference of 16.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters equivalent between treated patients and natural history controls (P < .01), “which [does] suggest that this effect is maintained,” said Dr. Newman, who is a professor of ophthalmology and neurology at Emory University, Atlanta.

Dr. Rost also wondered if it would be possible to capture patients earlier in their disease process, in the hopes of countering degeneration before it becomes severe enough to impact vision. Dr. Newman answered by noting another surprise from the research. Previous studies had shown that intervention while only a single eye is affected had little impact on spread of the condition to the second eye, “which was very disappointing,” said Dr. Newman. When they stratified patients by time since vision loss, they found that those who received the therapy 6 months or later after vision loss had better responses than those who were treated earlier.

The mechanism of this counter-intuitive finding remains uncertain, “but we do know that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Our hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better,” said Dr. Newman.

The study included patients at 13 sites worldwide; 48 were treated bilaterally and 50 treated unilaterally. Just under 80% were male, the mean age was 31.5 years, and the mean duration of vision loss was 8.30 months.

After 1.5 years, the improvement in best-corrected visual acuity between second-affected eyes was stronger in the treatment eye, equivalent to +3 ETDRS letters. The first-affected eye improved by 19 ETDRS letters, and the second-affected eye improved by 16 (P < .0001). Improvement in placebo eyes was +13 ETDRS letters (P < .0001).

Dr. Rost has served on a scientific advisory board or data monitoring board for Omniox. Dr. Newman has consulted for GenSight, Santhera/Chiesi, and Neurophoenix, and has received research support from GenSight and Santhera/Chiesi.

SEATTLE – The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene.

LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.

The study protocol called for injection of the therapy into one eye and a placebo into the other, using the patient as his or own placebo control. The results in the treated eye were encouraging, though modest. “This is not hitting it out of the ballpark. But for people whose vision is devastated by this disease, it certainly is a first step,” said Nancy J. Newman, MD, during a press conference held March 29 in advance of the 2022 annual meeting of the American Academy of Neurology.

Dr. Newman also noted a surprise finding: Visual improvement also occurred in the placebo-control eye. This was noted in previous studies, called RESCUE and REVERSE, and follow-up studies in monkeys found viral vector in the unaffected eye 3-6 months after an injection. “This would imply some kind of transport within retrograde up the opposite optic nerve after crossing in the chiasm to the eye, but this is going to take a fair bit of work to know exactly how that happens,” said Dr. Newman

Unfortunately, the phase 3 REFLECT study was designed before that process was understood. “This was not a case-control study by person, it was by eye. And that was a mistake, because it turns out there is a does appear to be second eye effects. We do not have naive controls here that did not receive any injection at all in any eye. That’s something that we will [do going] forward,” said Dr. Newman.

Despite the problem with placebo, the results were encouraging. “Those patients who had both eyes injected with the drug did better than in those who had one eye injected with drug and one eye injected with placebo, suggesting some sort of dose effect. There were no adverse events other than what we would expect from injecting [into] eyes. Those treated with the drug had more ocular inflammation, as would also be expected, but all were easily treated with topical medications,” said Dr. Newman.
 

What are the long-term effects?

Natalia Rost, MD, who chairs the AAN Science Committee, commented after the presentation: “We’re quite impressed with advances in gene therapy. The question is, are there early indications that this improvement in vision will have a lasting effect?”

Dr. Newman responded that ongoing data from earlier studies are also encouraging regarding the long-term effect of the treatment. At 4 years, there was a difference of 16.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters equivalent between treated patients and natural history controls (P < .01), “which [does] suggest that this effect is maintained,” said Dr. Newman, who is a professor of ophthalmology and neurology at Emory University, Atlanta.

Dr. Rost also wondered if it would be possible to capture patients earlier in their disease process, in the hopes of countering degeneration before it becomes severe enough to impact vision. Dr. Newman answered by noting another surprise from the research. Previous studies had shown that intervention while only a single eye is affected had little impact on spread of the condition to the second eye, “which was very disappointing,” said Dr. Newman. When they stratified patients by time since vision loss, they found that those who received the therapy 6 months or later after vision loss had better responses than those who were treated earlier.

The mechanism of this counter-intuitive finding remains uncertain, “but we do know that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Our hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better,” said Dr. Newman.

The study included patients at 13 sites worldwide; 48 were treated bilaterally and 50 treated unilaterally. Just under 80% were male, the mean age was 31.5 years, and the mean duration of vision loss was 8.30 months.

After 1.5 years, the improvement in best-corrected visual acuity between second-affected eyes was stronger in the treatment eye, equivalent to +3 ETDRS letters. The first-affected eye improved by 19 ETDRS letters, and the second-affected eye improved by 16 (P < .0001). Improvement in placebo eyes was +13 ETDRS letters (P < .0001).

Dr. Rost has served on a scientific advisory board or data monitoring board for Omniox. Dr. Newman has consulted for GenSight, Santhera/Chiesi, and Neurophoenix, and has received research support from GenSight and Santhera/Chiesi.

SEATTLE – The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene.

LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.

The study protocol called for injection of the therapy into one eye and a placebo into the other, using the patient as his or own placebo control. The results in the treated eye were encouraging, though modest. “This is not hitting it out of the ballpark. But for people whose vision is devastated by this disease, it certainly is a first step,” said Nancy J. Newman, MD, during a press conference held March 29 in advance of the 2022 annual meeting of the American Academy of Neurology.

Dr. Newman also noted a surprise finding: Visual improvement also occurred in the placebo-control eye. This was noted in previous studies, called RESCUE and REVERSE, and follow-up studies in monkeys found viral vector in the unaffected eye 3-6 months after an injection. “This would imply some kind of transport within retrograde up the opposite optic nerve after crossing in the chiasm to the eye, but this is going to take a fair bit of work to know exactly how that happens,” said Dr. Newman

Unfortunately, the phase 3 REFLECT study was designed before that process was understood. “This was not a case-control study by person, it was by eye. And that was a mistake, because it turns out there is a does appear to be second eye effects. We do not have naive controls here that did not receive any injection at all in any eye. That’s something that we will [do going] forward,” said Dr. Newman.

Despite the problem with placebo, the results were encouraging. “Those patients who had both eyes injected with the drug did better than in those who had one eye injected with drug and one eye injected with placebo, suggesting some sort of dose effect. There were no adverse events other than what we would expect from injecting [into] eyes. Those treated with the drug had more ocular inflammation, as would also be expected, but all were easily treated with topical medications,” said Dr. Newman.
 

What are the long-term effects?

Natalia Rost, MD, who chairs the AAN Science Committee, commented after the presentation: “We’re quite impressed with advances in gene therapy. The question is, are there early indications that this improvement in vision will have a lasting effect?”

Dr. Newman responded that ongoing data from earlier studies are also encouraging regarding the long-term effect of the treatment. At 4 years, there was a difference of 16.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters equivalent between treated patients and natural history controls (P < .01), “which [does] suggest that this effect is maintained,” said Dr. Newman, who is a professor of ophthalmology and neurology at Emory University, Atlanta.

Dr. Rost also wondered if it would be possible to capture patients earlier in their disease process, in the hopes of countering degeneration before it becomes severe enough to impact vision. Dr. Newman answered by noting another surprise from the research. Previous studies had shown that intervention while only a single eye is affected had little impact on spread of the condition to the second eye, “which was very disappointing,” said Dr. Newman. When they stratified patients by time since vision loss, they found that those who received the therapy 6 months or later after vision loss had better responses than those who were treated earlier.

The mechanism of this counter-intuitive finding remains uncertain, “but we do know that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Our hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better,” said Dr. Newman.

The study included patients at 13 sites worldwide; 48 were treated bilaterally and 50 treated unilaterally. Just under 80% were male, the mean age was 31.5 years, and the mean duration of vision loss was 8.30 months.

After 1.5 years, the improvement in best-corrected visual acuity between second-affected eyes was stronger in the treatment eye, equivalent to +3 ETDRS letters. The first-affected eye improved by 19 ETDRS letters, and the second-affected eye improved by 16 (P < .0001). Improvement in placebo eyes was +13 ETDRS letters (P < .0001).

Dr. Rost has served on a scientific advisory board or data monitoring board for Omniox. Dr. Newman has consulted for GenSight, Santhera/Chiesi, and Neurophoenix, and has received research support from GenSight and Santhera/Chiesi.

The short interfering RNA (siRNA) agent SLN360 was well tolerated and lowered lipoprotein(a) by up to 98% in volunteers without cardiovascular disease but with elevated Lp(a) in the small dose-ranging APOLLO trial.

Following a single subcutaneous dose of SLN360 (Silence Therapeutics), there was a dose-dependent reduction in Lp(a) plasma levels by a median of 46%, 86%, 96%, and 98% at about 45-60 days with 30-mg, 100-mg, 300-mg, and 600-mg doses, respectively.

Lp(a) levels at 150 days were 70% and 81% below baseline with the 300-and 600-mg doses.

In addition, for participants receiving the two highest doses, apolipoprotein B (apo B) was reduced was 21% and 24%, respectively, and LDL cholesterol (LDL-C), by 21% and 26%, respectively.

“The development of therapies targeting messenger RNA has made possible significant lowering of lipoprotein(a). Whether these reductions can impact on the incidence of ASCVD [atherosclerotic cardiovascular disease] or prevent progression of aortic stenosis remains to be determined but, we think, that optimism is warranted,” said principal investigator Steven E. Nissen, MD, Cleveland Clinic.

The results were presented in a late-breaking clinical trial session at the annual scientific sessions of the American College of Cardiology and published simultaneously in JAMA.

Elevated Lp(a) is a powerful genetic risk factor for ASCVD and aortic stenosis, which affects some 64 million Americans and 1.4 billion people globally. Although several experimental agents are under investigation, no currently approved drugs selectively lower Lp(a).

SLN360 is designed to lower Lp(a) production by using RNA interference to silence messenger RNA transcribed from the LPA gene in liver cells.
 

Testing vacuum

Dr. Nissen said in an interview that one of the big takeaways from the study is the need for greater testing of Lp(a). Automatic assays are available in almost every hospital, but two-unit systems (nmol/L and mg/dL) are used and thresholds for accelerated risk vary. The Cleveland Clinic currently tests all patients in its cardiac critical care unit and its prevention clinic.

“Someone comes in with an MI in their 40s and we measure it and it’s 100, 150 [mg/dL], clearly abnormal, and often these patients don’t have a lot of other risk factors,” Dr. Nissen said. “So the explanation very likely for their premature disease is this risk factor. We now have to educate everybody about the importance of getting it tested and finding out about it.”

During a media briefing, ACC 2022 program cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said testing for Lp(a) is not well reimbursed by insurance providers and that her patients will often cancel the test after learning it won’t be reimbursed because they don’t understand it.

“What Dr. Nissen is telling you: It should be measured in everyone at least once, we all believe that, but it hasn’t made it into the major guidelines,” she added. “I think what we’re going to have to do is have the guidelines mandate it and the insurers will follow.”

Guidelines currently list elevated Lp(a) as a “risk-enhancing factor,” which can help with at least recommending LDL-C treatment in patients with borderline risk and a sky-high Lp(a), noted Dr. Nissen. “But we need to go beyond that.”
 

Safety analyses

The first-in-human APOLLO trial evaluated 32 adults without known ASCVD and an Lp(a) concentration greater than 150 nmol/L (approximately 60 mg/dL) who received one of the four doses of SLN360 or placebo subcutaneously. Participants were monitored in a research unit for the first 24 hours and then followed periodically for up to 150 days. At baseline, their median Lp(a) level was 224 nmol/L, mean apo B level was 85 mg/dL, and mean LDL-C level was 108 mg/dL.

Treatment-emergent adverse events were generally mild, mostly grade 1 injection site reactions (83% at 30 mg, 100% at 100 mg, 67% at 300 mg, and 33% at 600 mg) and headache (33%, 17%, 0%, and 83%).

At the highest dose, C-reactive protein was increased in four patients and neutrophil counts in three. ALT and AST levels were elevated three times above the upper limit of normal in one patient at the lowest dose.

One participant in the lowest-dose group experienced two serious adverse events unrelated to SLN360 at day 45 after receiving a SARS-Co-V-2 vaccine.

Dr. Nissen noted that safety cannot be comprehensively assessed in a trial of this duration or size and that follow-up has been extended to 1 year in the two highest-dose groups.

Enrollment continues in the multiple-ascending dose portion of the study in patients with high Lp(a) and a history of stable ASCVD. A phase 2 study of SLN360 is also planned for the second half of 2022, pending regulatory discussions.
 

But will it reduce ASCVD events?

Study discussant Vera Bittner, MD, MSPH, University of Alabama at Birmingham, said that the development of Lp(a)-specific lowering agents has been a “holy grail” for years and congratulated the authors on a successful trial demonstrating very robust Lp(a) lowering.

She asked Dr. Nissen about the observation in proprotein convertase subtilisin/kexin type 9 inhibitor trials that absolute Lp(a) lowering is greater at higher baseline levels.

Dr. Nissen said this kind of analysis wasn’t possible because of the small sample size but “because these agents so effectively degrade messenger RNA, it’s very likely we will see robust suppression of plasma levels virtually regardless of the baseline level.”

Dr. Bittner also questioned if “LDL-C declined because of the cholesterol content in the lipoprotein(a) or is there some additional effect on LDL particles themselves?”

“It’s a really terrific question that will ultimately need to be answered,” Dr. Nissen replied. “There’s some controversy about the extent to which suppressing lipoprotein(a) will reduce LDL because the assays for LDL are measuring the LDL that’s in lipoprotein(a) and the LDL that is not. ... I think it’s probably a bystander effect, but it may also contribute to efficacy from a morbidity and mortality point of view, which is why we measured it.”

Dr. Bittner also called out the elevation in C-reactive protein and leukocytosis, which has not been seen in other siRNA studies. Dr. Nissen said the increases in C-reactive protein occurred in the first few days after administration and were gone after a week or so. “I don’t see it as a long-term limitation.”

In an accompanying editorial, Brian Ference, MD, MPhil, MSc, University of Cambridge (England), suggests that because circulating Lp(a) particles can progressively become trapped within the artery wall over time, it’s unlikely that lowering Lp(a) for only a few years starting later in life will eliminate the effect of lifelong exposure to Lp(a) and may only cut cardiovascular event risk by about 10%-15%.

He called for continued safety and efficacy evaluation of SLN360 and olpasiran, a similar siRNA agent in early development, and said further insights into whether large absolute reductions in Lp(a) can reduce the risk for major cardiovascular events will come from cardiovascular trials, such as the ongoing phase 3 Lp(a)HORIZON trial. It follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and has Dr. Nissen pulling double duty as study chair.

The study was funded by Silence Therapeutics. Dr. Nissen reported consulting for many pharmaceutical companies, which are directed to pay any renumeration directly to charity. Dr. Bittner reported consultant fees or honoraria from Pfizer; other from AstraZeneca, DalCor, Esperion, and Sanofi-Aventis; and research/research grants from Amgen and Novartis. Dr. Ference reported financial ties to Merck, Novartis, Amgen, Pfizer, Esperion Therapeutics, and numerous other companies.

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

The short interfering RNA (siRNA) agent SLN360 was well tolerated and lowered lipoprotein(a) by up to 98% in volunteers without cardiovascular disease but with elevated Lp(a) in the small dose-ranging APOLLO trial.

Following a single subcutaneous dose of SLN360 (Silence Therapeutics), there was a dose-dependent reduction in Lp(a) plasma levels by a median of 46%, 86%, 96%, and 98% at about 45-60 days with 30-mg, 100-mg, 300-mg, and 600-mg doses, respectively.

Lp(a) levels at 150 days were 70% and 81% below baseline with the 300-and 600-mg doses.

In addition, for participants receiving the two highest doses, apolipoprotein B (apo B) was reduced was 21% and 24%, respectively, and LDL cholesterol (LDL-C), by 21% and 26%, respectively.

“The development of therapies targeting messenger RNA has made possible significant lowering of lipoprotein(a). Whether these reductions can impact on the incidence of ASCVD [atherosclerotic cardiovascular disease] or prevent progression of aortic stenosis remains to be determined but, we think, that optimism is warranted,” said principal investigator Steven E. Nissen, MD, Cleveland Clinic.

The results were presented in a late-breaking clinical trial session at the annual scientific sessions of the American College of Cardiology and published simultaneously in JAMA.

Elevated Lp(a) is a powerful genetic risk factor for ASCVD and aortic stenosis, which affects some 64 million Americans and 1.4 billion people globally. Although several experimental agents are under investigation, no currently approved drugs selectively lower Lp(a).

SLN360 is designed to lower Lp(a) production by using RNA interference to silence messenger RNA transcribed from the LPA gene in liver cells.
 

Testing vacuum

Dr. Nissen said in an interview that one of the big takeaways from the study is the need for greater testing of Lp(a). Automatic assays are available in almost every hospital, but two-unit systems (nmol/L and mg/dL) are used and thresholds for accelerated risk vary. The Cleveland Clinic currently tests all patients in its cardiac critical care unit and its prevention clinic.

“Someone comes in with an MI in their 40s and we measure it and it’s 100, 150 [mg/dL], clearly abnormal, and often these patients don’t have a lot of other risk factors,” Dr. Nissen said. “So the explanation very likely for their premature disease is this risk factor. We now have to educate everybody about the importance of getting it tested and finding out about it.”

During a media briefing, ACC 2022 program cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said testing for Lp(a) is not well reimbursed by insurance providers and that her patients will often cancel the test after learning it won’t be reimbursed because they don’t understand it.

“What Dr. Nissen is telling you: It should be measured in everyone at least once, we all believe that, but it hasn’t made it into the major guidelines,” she added. “I think what we’re going to have to do is have the guidelines mandate it and the insurers will follow.”

Guidelines currently list elevated Lp(a) as a “risk-enhancing factor,” which can help with at least recommending LDL-C treatment in patients with borderline risk and a sky-high Lp(a), noted Dr. Nissen. “But we need to go beyond that.”
 

Safety analyses

The first-in-human APOLLO trial evaluated 32 adults without known ASCVD and an Lp(a) concentration greater than 150 nmol/L (approximately 60 mg/dL) who received one of the four doses of SLN360 or placebo subcutaneously. Participants were monitored in a research unit for the first 24 hours and then followed periodically for up to 150 days. At baseline, their median Lp(a) level was 224 nmol/L, mean apo B level was 85 mg/dL, and mean LDL-C level was 108 mg/dL.

Treatment-emergent adverse events were generally mild, mostly grade 1 injection site reactions (83% at 30 mg, 100% at 100 mg, 67% at 300 mg, and 33% at 600 mg) and headache (33%, 17%, 0%, and 83%).

At the highest dose, C-reactive protein was increased in four patients and neutrophil counts in three. ALT and AST levels were elevated three times above the upper limit of normal in one patient at the lowest dose.

One participant in the lowest-dose group experienced two serious adverse events unrelated to SLN360 at day 45 after receiving a SARS-Co-V-2 vaccine.

Dr. Nissen noted that safety cannot be comprehensively assessed in a trial of this duration or size and that follow-up has been extended to 1 year in the two highest-dose groups.

Enrollment continues in the multiple-ascending dose portion of the study in patients with high Lp(a) and a history of stable ASCVD. A phase 2 study of SLN360 is also planned for the second half of 2022, pending regulatory discussions.
 

But will it reduce ASCVD events?

Study discussant Vera Bittner, MD, MSPH, University of Alabama at Birmingham, said that the development of Lp(a)-specific lowering agents has been a “holy grail” for years and congratulated the authors on a successful trial demonstrating very robust Lp(a) lowering.

She asked Dr. Nissen about the observation in proprotein convertase subtilisin/kexin type 9 inhibitor trials that absolute Lp(a) lowering is greater at higher baseline levels.

Dr. Nissen said this kind of analysis wasn’t possible because of the small sample size but “because these agents so effectively degrade messenger RNA, it’s very likely we will see robust suppression of plasma levels virtually regardless of the baseline level.”

Dr. Bittner also questioned if “LDL-C declined because of the cholesterol content in the lipoprotein(a) or is there some additional effect on LDL particles themselves?”

“It’s a really terrific question that will ultimately need to be answered,” Dr. Nissen replied. “There’s some controversy about the extent to which suppressing lipoprotein(a) will reduce LDL because the assays for LDL are measuring the LDL that’s in lipoprotein(a) and the LDL that is not. ... I think it’s probably a bystander effect, but it may also contribute to efficacy from a morbidity and mortality point of view, which is why we measured it.”

Dr. Bittner also called out the elevation in C-reactive protein and leukocytosis, which has not been seen in other siRNA studies. Dr. Nissen said the increases in C-reactive protein occurred in the first few days after administration and were gone after a week or so. “I don’t see it as a long-term limitation.”

In an accompanying editorial, Brian Ference, MD, MPhil, MSc, University of Cambridge (England), suggests that because circulating Lp(a) particles can progressively become trapped within the artery wall over time, it’s unlikely that lowering Lp(a) for only a few years starting later in life will eliminate the effect of lifelong exposure to Lp(a) and may only cut cardiovascular event risk by about 10%-15%.

He called for continued safety and efficacy evaluation of SLN360 and olpasiran, a similar siRNA agent in early development, and said further insights into whether large absolute reductions in Lp(a) can reduce the risk for major cardiovascular events will come from cardiovascular trials, such as the ongoing phase 3 Lp(a)HORIZON trial. It follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and has Dr. Nissen pulling double duty as study chair.

The study was funded by Silence Therapeutics. Dr. Nissen reported consulting for many pharmaceutical companies, which are directed to pay any renumeration directly to charity. Dr. Bittner reported consultant fees or honoraria from Pfizer; other from AstraZeneca, DalCor, Esperion, and Sanofi-Aventis; and research/research grants from Amgen and Novartis. Dr. Ference reported financial ties to Merck, Novartis, Amgen, Pfizer, Esperion Therapeutics, and numerous other companies.

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

The short interfering RNA (siRNA) agent SLN360 was well tolerated and lowered lipoprotein(a) by up to 98% in volunteers without cardiovascular disease but with elevated Lp(a) in the small dose-ranging APOLLO trial.

Following a single subcutaneous dose of SLN360 (Silence Therapeutics), there was a dose-dependent reduction in Lp(a) plasma levels by a median of 46%, 86%, 96%, and 98% at about 45-60 days with 30-mg, 100-mg, 300-mg, and 600-mg doses, respectively.

Lp(a) levels at 150 days were 70% and 81% below baseline with the 300-and 600-mg doses.

In addition, for participants receiving the two highest doses, apolipoprotein B (apo B) was reduced was 21% and 24%, respectively, and LDL cholesterol (LDL-C), by 21% and 26%, respectively.

“The development of therapies targeting messenger RNA has made possible significant lowering of lipoprotein(a). Whether these reductions can impact on the incidence of ASCVD [atherosclerotic cardiovascular disease] or prevent progression of aortic stenosis remains to be determined but, we think, that optimism is warranted,” said principal investigator Steven E. Nissen, MD, Cleveland Clinic.

The results were presented in a late-breaking clinical trial session at the annual scientific sessions of the American College of Cardiology and published simultaneously in JAMA.

Elevated Lp(a) is a powerful genetic risk factor for ASCVD and aortic stenosis, which affects some 64 million Americans and 1.4 billion people globally. Although several experimental agents are under investigation, no currently approved drugs selectively lower Lp(a).

SLN360 is designed to lower Lp(a) production by using RNA interference to silence messenger RNA transcribed from the LPA gene in liver cells.
 

Testing vacuum

Dr. Nissen said in an interview that one of the big takeaways from the study is the need for greater testing of Lp(a). Automatic assays are available in almost every hospital, but two-unit systems (nmol/L and mg/dL) are used and thresholds for accelerated risk vary. The Cleveland Clinic currently tests all patients in its cardiac critical care unit and its prevention clinic.

“Someone comes in with an MI in their 40s and we measure it and it’s 100, 150 [mg/dL], clearly abnormal, and often these patients don’t have a lot of other risk factors,” Dr. Nissen said. “So the explanation very likely for their premature disease is this risk factor. We now have to educate everybody about the importance of getting it tested and finding out about it.”

During a media briefing, ACC 2022 program cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said testing for Lp(a) is not well reimbursed by insurance providers and that her patients will often cancel the test after learning it won’t be reimbursed because they don’t understand it.

“What Dr. Nissen is telling you: It should be measured in everyone at least once, we all believe that, but it hasn’t made it into the major guidelines,” she added. “I think what we’re going to have to do is have the guidelines mandate it and the insurers will follow.”

Guidelines currently list elevated Lp(a) as a “risk-enhancing factor,” which can help with at least recommending LDL-C treatment in patients with borderline risk and a sky-high Lp(a), noted Dr. Nissen. “But we need to go beyond that.”
 

Safety analyses

The first-in-human APOLLO trial evaluated 32 adults without known ASCVD and an Lp(a) concentration greater than 150 nmol/L (approximately 60 mg/dL) who received one of the four doses of SLN360 or placebo subcutaneously. Participants were monitored in a research unit for the first 24 hours and then followed periodically for up to 150 days. At baseline, their median Lp(a) level was 224 nmol/L, mean apo B level was 85 mg/dL, and mean LDL-C level was 108 mg/dL.

Treatment-emergent adverse events were generally mild, mostly grade 1 injection site reactions (83% at 30 mg, 100% at 100 mg, 67% at 300 mg, and 33% at 600 mg) and headache (33%, 17%, 0%, and 83%).

At the highest dose, C-reactive protein was increased in four patients and neutrophil counts in three. ALT and AST levels were elevated three times above the upper limit of normal in one patient at the lowest dose.

One participant in the lowest-dose group experienced two serious adverse events unrelated to SLN360 at day 45 after receiving a SARS-Co-V-2 vaccine.

Dr. Nissen noted that safety cannot be comprehensively assessed in a trial of this duration or size and that follow-up has been extended to 1 year in the two highest-dose groups.

Enrollment continues in the multiple-ascending dose portion of the study in patients with high Lp(a) and a history of stable ASCVD. A phase 2 study of SLN360 is also planned for the second half of 2022, pending regulatory discussions.
 

But will it reduce ASCVD events?

Study discussant Vera Bittner, MD, MSPH, University of Alabama at Birmingham, said that the development of Lp(a)-specific lowering agents has been a “holy grail” for years and congratulated the authors on a successful trial demonstrating very robust Lp(a) lowering.

She asked Dr. Nissen about the observation in proprotein convertase subtilisin/kexin type 9 inhibitor trials that absolute Lp(a) lowering is greater at higher baseline levels.

Dr. Nissen said this kind of analysis wasn’t possible because of the small sample size but “because these agents so effectively degrade messenger RNA, it’s very likely we will see robust suppression of plasma levels virtually regardless of the baseline level.”

Dr. Bittner also questioned if “LDL-C declined because of the cholesterol content in the lipoprotein(a) or is there some additional effect on LDL particles themselves?”

“It’s a really terrific question that will ultimately need to be answered,” Dr. Nissen replied. “There’s some controversy about the extent to which suppressing lipoprotein(a) will reduce LDL because the assays for LDL are measuring the LDL that’s in lipoprotein(a) and the LDL that is not. ... I think it’s probably a bystander effect, but it may also contribute to efficacy from a morbidity and mortality point of view, which is why we measured it.”

Dr. Bittner also called out the elevation in C-reactive protein and leukocytosis, which has not been seen in other siRNA studies. Dr. Nissen said the increases in C-reactive protein occurred in the first few days after administration and were gone after a week or so. “I don’t see it as a long-term limitation.”

In an accompanying editorial, Brian Ference, MD, MPhil, MSc, University of Cambridge (England), suggests that because circulating Lp(a) particles can progressively become trapped within the artery wall over time, it’s unlikely that lowering Lp(a) for only a few years starting later in life will eliminate the effect of lifelong exposure to Lp(a) and may only cut cardiovascular event risk by about 10%-15%.

He called for continued safety and efficacy evaluation of SLN360 and olpasiran, a similar siRNA agent in early development, and said further insights into whether large absolute reductions in Lp(a) can reduce the risk for major cardiovascular events will come from cardiovascular trials, such as the ongoing phase 3 Lp(a)HORIZON trial. It follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and has Dr. Nissen pulling double duty as study chair.

The study was funded by Silence Therapeutics. Dr. Nissen reported consulting for many pharmaceutical companies, which are directed to pay any renumeration directly to charity. Dr. Bittner reported consultant fees or honoraria from Pfizer; other from AstraZeneca, DalCor, Esperion, and Sanofi-Aventis; and research/research grants from Amgen and Novartis. Dr. Ference reported financial ties to Merck, Novartis, Amgen, Pfizer, Esperion Therapeutics, and numerous other companies.

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