Ob.Gyn. News

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

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

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

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

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

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

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

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

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

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

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

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

Despite recent reports of Guillain-Barré Syndrome (GBS) after the Johnson & Johnson vaccine, independent experts who advise the Centers for Disease Control and Prevention on the use of vaccines agree that the benefits of the one-dose shot still outweigh its risks.

Johnson & Johnson

The company also presented new data suggesting that the shots generate strong immune responses against circulating variants and that antibodies generated by the vaccine stay elevated for at least 8 months.

Members of the Advisory Committee on Immunization Practices (ACIP) did not vote, but discussed and affirmed their support for recent decisions by the Food and Drug Administration and CDC to update patient information about the very low risk of GBS that appears to be associated with the vaccine, but to continue offering the vaccine to people in the United States.

The Johnson & Johnson shot has been a minor player in the U.S. vaccination campaign, accounting for less than 4% of all vaccine doses given in this country. Still, the single-dose inoculation, which doesn’t require ultra-cold storage, has been important for reaching people in rural areas, through mobile clinics, at colleges and primary care offices, and in vulnerable populations – those who are incarcerated or homeless.

The FDA says it has received reports of 100 cases of GBS after the Johnson & Johnson vaccine in its Vaccine Adverse Event Reporting System database through the end of June. The cases are still under investigation.

To date, more than 12 million doses of the vaccine have been administered, making the rate of GBS 8.1 cases for every million doses administered.

Although it is still extremely rare, that’s above the expected background rate of GBS of 1.6 cases for every million people, said Grace Lee, MD, a Stanford, Calif., pediatrician who chairs the ACIP’s Vaccine Safety Technical Work Group. 

So far, most GBS cases (61%) have been among men. The midpoint age of the cases was 57 years. The average time to onset was 14 days, and 98% of cases occurred within 42 days of the shot.  Facial paralysis has been associated with an estimated 30%-50% of cases. One person, who had heart failure, high blood pressure, and diabetes, has died.

Still, the benefits of the vaccine far outweigh its risks. For every million doses given to people over age 50, the vaccine prevents nearly 7,500 COVID-19 hospitalizations and nearly 100 deaths in women, and more than 13,000 COVID-19 hospitalizations and more than 2,400 deaths in men. 

Rates of GBS after the mRNA vaccines made by Pfizer and Moderna were around 1 case for every 1 million doses given, which is not above the rate that would be expected without vaccination.

The link to the Johnson & Johnson vaccine prompted the FDA to add a warning to the vaccine’s patient safety information on July 12.

Also in July, the European Medicines Agency recommended a similar warning for the product information of the AstraZeneca vaccine Vaxzevria, which relies on similar technology.
 

Good against variants

Johnson & Johnson also presented new information showing its vaccine maintained high levels of neutralizing antibodies against four of the so-called “variants of concern” – Alpha, Gamma, Beta, and Delta. The protection generated by the vaccine lasted for at least 8 months after the shot, the company said.

“We’re still learning about the duration of protection and the breadth of coverage against this evolving variant landscape for each of the authorized vaccines,” said Mathai Mammen, MD, PhD, global head of research and development at Janssen, the company that makes the vaccine for J&J.

The company also said that its vaccine generated very strong T-cell responses. T cells destroy infected cells and, along with antibodies, are an important part of the body’s immune response.

Antibody levels and T-cell responses are markers for immunity. Measuring these levels isn’t the same as proving that shots can fend off an infection. 

It’s still unclear exactly which component of the immune response is most important for fighting off COVID-19.

Dr. Mammen said the companies are still gathering that clinical data, and would present it soon.

“We will have a better view of the clinical efficacy in the coming weeks,” he said.


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

Despite recent reports of Guillain-Barré Syndrome (GBS) after the Johnson & Johnson vaccine, independent experts who advise the Centers for Disease Control and Prevention on the use of vaccines agree that the benefits of the one-dose shot still outweigh its risks.

Johnson & Johnson

The company also presented new data suggesting that the shots generate strong immune responses against circulating variants and that antibodies generated by the vaccine stay elevated for at least 8 months.

Members of the Advisory Committee on Immunization Practices (ACIP) did not vote, but discussed and affirmed their support for recent decisions by the Food and Drug Administration and CDC to update patient information about the very low risk of GBS that appears to be associated with the vaccine, but to continue offering the vaccine to people in the United States.

The Johnson & Johnson shot has been a minor player in the U.S. vaccination campaign, accounting for less than 4% of all vaccine doses given in this country. Still, the single-dose inoculation, which doesn’t require ultra-cold storage, has been important for reaching people in rural areas, through mobile clinics, at colleges and primary care offices, and in vulnerable populations – those who are incarcerated or homeless.

The FDA says it has received reports of 100 cases of GBS after the Johnson & Johnson vaccine in its Vaccine Adverse Event Reporting System database through the end of June. The cases are still under investigation.

To date, more than 12 million doses of the vaccine have been administered, making the rate of GBS 8.1 cases for every million doses administered.

Although it is still extremely rare, that’s above the expected background rate of GBS of 1.6 cases for every million people, said Grace Lee, MD, a Stanford, Calif., pediatrician who chairs the ACIP’s Vaccine Safety Technical Work Group. 

So far, most GBS cases (61%) have been among men. The midpoint age of the cases was 57 years. The average time to onset was 14 days, and 98% of cases occurred within 42 days of the shot.  Facial paralysis has been associated with an estimated 30%-50% of cases. One person, who had heart failure, high blood pressure, and diabetes, has died.

Still, the benefits of the vaccine far outweigh its risks. For every million doses given to people over age 50, the vaccine prevents nearly 7,500 COVID-19 hospitalizations and nearly 100 deaths in women, and more than 13,000 COVID-19 hospitalizations and more than 2,400 deaths in men. 

Rates of GBS after the mRNA vaccines made by Pfizer and Moderna were around 1 case for every 1 million doses given, which is not above the rate that would be expected without vaccination.

The link to the Johnson & Johnson vaccine prompted the FDA to add a warning to the vaccine’s patient safety information on July 12.

Also in July, the European Medicines Agency recommended a similar warning for the product information of the AstraZeneca vaccine Vaxzevria, which relies on similar technology.
 

Good against variants

Johnson & Johnson also presented new information showing its vaccine maintained high levels of neutralizing antibodies against four of the so-called “variants of concern” – Alpha, Gamma, Beta, and Delta. The protection generated by the vaccine lasted for at least 8 months after the shot, the company said.

“We’re still learning about the duration of protection and the breadth of coverage against this evolving variant landscape for each of the authorized vaccines,” said Mathai Mammen, MD, PhD, global head of research and development at Janssen, the company that makes the vaccine for J&J.

The company also said that its vaccine generated very strong T-cell responses. T cells destroy infected cells and, along with antibodies, are an important part of the body’s immune response.

Antibody levels and T-cell responses are markers for immunity. Measuring these levels isn’t the same as proving that shots can fend off an infection. 

It’s still unclear exactly which component of the immune response is most important for fighting off COVID-19.

Dr. Mammen said the companies are still gathering that clinical data, and would present it soon.

“We will have a better view of the clinical efficacy in the coming weeks,” he said.


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

Despite recent reports of Guillain-Barré Syndrome (GBS) after the Johnson & Johnson vaccine, independent experts who advise the Centers for Disease Control and Prevention on the use of vaccines agree that the benefits of the one-dose shot still outweigh its risks.

Johnson & Johnson

The company also presented new data suggesting that the shots generate strong immune responses against circulating variants and that antibodies generated by the vaccine stay elevated for at least 8 months.

Members of the Advisory Committee on Immunization Practices (ACIP) did not vote, but discussed and affirmed their support for recent decisions by the Food and Drug Administration and CDC to update patient information about the very low risk of GBS that appears to be associated with the vaccine, but to continue offering the vaccine to people in the United States.

The Johnson & Johnson shot has been a minor player in the U.S. vaccination campaign, accounting for less than 4% of all vaccine doses given in this country. Still, the single-dose inoculation, which doesn’t require ultra-cold storage, has been important for reaching people in rural areas, through mobile clinics, at colleges and primary care offices, and in vulnerable populations – those who are incarcerated or homeless.

The FDA says it has received reports of 100 cases of GBS after the Johnson & Johnson vaccine in its Vaccine Adverse Event Reporting System database through the end of June. The cases are still under investigation.

To date, more than 12 million doses of the vaccine have been administered, making the rate of GBS 8.1 cases for every million doses administered.

Although it is still extremely rare, that’s above the expected background rate of GBS of 1.6 cases for every million people, said Grace Lee, MD, a Stanford, Calif., pediatrician who chairs the ACIP’s Vaccine Safety Technical Work Group. 

So far, most GBS cases (61%) have been among men. The midpoint age of the cases was 57 years. The average time to onset was 14 days, and 98% of cases occurred within 42 days of the shot.  Facial paralysis has been associated with an estimated 30%-50% of cases. One person, who had heart failure, high blood pressure, and diabetes, has died.

Still, the benefits of the vaccine far outweigh its risks. For every million doses given to people over age 50, the vaccine prevents nearly 7,500 COVID-19 hospitalizations and nearly 100 deaths in women, and more than 13,000 COVID-19 hospitalizations and more than 2,400 deaths in men. 

Rates of GBS after the mRNA vaccines made by Pfizer and Moderna were around 1 case for every 1 million doses given, which is not above the rate that would be expected without vaccination.

The link to the Johnson & Johnson vaccine prompted the FDA to add a warning to the vaccine’s patient safety information on July 12.

Also in July, the European Medicines Agency recommended a similar warning for the product information of the AstraZeneca vaccine Vaxzevria, which relies on similar technology.
 

Good against variants

Johnson & Johnson also presented new information showing its vaccine maintained high levels of neutralizing antibodies against four of the so-called “variants of concern” – Alpha, Gamma, Beta, and Delta. The protection generated by the vaccine lasted for at least 8 months after the shot, the company said.

“We’re still learning about the duration of protection and the breadth of coverage against this evolving variant landscape for each of the authorized vaccines,” said Mathai Mammen, MD, PhD, global head of research and development at Janssen, the company that makes the vaccine for J&J.

The company also said that its vaccine generated very strong T-cell responses. T cells destroy infected cells and, along with antibodies, are an important part of the body’s immune response.

Antibody levels and T-cell responses are markers for immunity. Measuring these levels isn’t the same as proving that shots can fend off an infection. 

It’s still unclear exactly which component of the immune response is most important for fighting off COVID-19.

Dr. Mammen said the companies are still gathering that clinical data, and would present it soon.

“We will have a better view of the clinical efficacy in the coming weeks,” he said.


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

Over the next 2 months we will dedicate this column to some general tips and pearls from the perspective of a gynecologic oncologist to guide general obstetrician gynecologists in the workup and management of preinvasive or invasive gynecologic diseases. The goal of these recommendations is to minimize misdiagnosis or delayed diagnosis and avoid unnecessary or untimely referrals.

Perform biopsy, not Pap smears, on visible cervical and vaginal lesions

The purpose of the Pap smear is to screen asymptomatic patients for cervical dysplasia or microscopic invasive disease. Cytology is an unreliable diagnostic tool for visible, symptomatic lesions in large part because of sampling errors, and the lack of architectural information in cytologic versus histopathologic specimens. Invasive lesions can be mischaracterized as preinvasive on a Pap smear. This can result in delayed diagnosis and unnecessary diagnostic procedures. For example, if a visible, abnormal-appearing, cervical lesion is seen during a routine visit and a Pap smear is performed (rather than a biopsy of the mass), the patient may receive an incorrect preliminary diagnosis of “high-grade dysplasia, carcinoma in situ” as it can be difficult to distinguish invasive carcinoma from carcinoma in situ on cytology. If the patient and provider do not understand the limitations of Pap smears in diagnosing invasive cancers, they may be falsely reassured and possibly delay or abstain from follow-up for an excisional procedure. If she does return for the loop electrosurgical excision procedure (LEEP), there might still be unnecessary delays in making referrals and definitive treatment while waiting for results. Radical hysterectomy may not promptly follow because, if performed within 6 weeks of an excisional procedure, it is associated with a significantly higher risk for perioperative complication, and therefore, if the excisional procedure was unnecessary to begin with, there may be additional time lost that need not be.¹

Some clinicians avoid biopsy of visible lesions because they are concerned about bleeding complications that might arise in the office. Straightforward strategies to control bleeding are readily available in most gynecology offices, especially those already equipped for procedures such as LEEP and colposcopy. Prior to performing the biopsy, clinicians should ensure that they have supplies such as gauze sponges and ring forceps or packing forceps, silver nitrate, and ferric subsulfate solution (“Monsel’s solution”) close at hand. In the vast majority of cases, direct pressure for 5 minutes with gauze sponges and ferric subsulfate is highly effective at resolving most bleeding from a cervical or vaginal biopsy site. If this does not bring hemostasis, cautery devices or suture can be employed. If all else fails, be prepared to place vaginal packing (always with the insertion of a urinary Foley catheter to prevent urinary retention). In my experience, this is rarely needed.

Wherever possible, visible cervical or vaginal (or vulvar, see below) lesions should be biopsied for histopathology, sampling representative areas of the most concerning portion, in order to minimize misdiagnosis and expedite referral and definitive treatment. For necrotic-appearing lesions I recommend taking multiple samples of the tumor, as necrotic, nonviable tissue can prevent accurate diagnosis of a cancer. In general, Pap smears should be reserved as screening tests for asymptomatic women without visible pathology.
 

Don’t treat or refer low-grade dysplasia, even if persistent

Increasingly we are understanding that low-grade dysplasia of the lower genital tract (CIN I, VAIN I, VIN I) is less a precursor for cancer, and more a phenomenon of benign HPV-associated changes.² This HPV change may be chronically persistent, may require years of observation and serial Pap smears, and may be a general nuisance for the patient. However, current guidelines do not recommend intervention for low-grade dysplasia of the lower genital tract.² Interventions to resect these lesions can result in morbidity, including perineal pain, vaginal scarring, and cervical stenosis or insufficiency. Given the extremely low risk for progression to cancer, these morbidities do not outweigh any small potential benefit.

When I am conferring with patients who have chronic low-grade dysplasia I spend a great deal of time exploring their understanding of the diagnosis and its pathophysiology, their fears, and their expectation regarding “success” of treatment. I spend the time educating them that this is a sequela of chronic viral infection that will not be eradicated with local surgical excisions, that their cancer risk and need for surveillance would persist even if surgical intervention were offered, and that the side effects of treatment would outweigh any benefit from the small risk of cancer or high-grade dysplasia.

In summary, the treatment of choice for persistent low-grade dysplasia of the lower genital tract is comprehensive patient education, not surgical resection or referral to gynecologic oncology.
 

Repeat sampling if there’s a discordance between imaging and biopsy results

Delay in cancer diagnosis is one of the greatest concerns for front-line gynecology providers. One of the more modifiable strategies to avoid missed or delayed diagnosis is to ensure that there is concordance between clinical findings and testing results. Otherwise said: The results and findings should make sense in aggregate. An example was cited above in which a visible cervical mass demonstrated CIN III on cytologic testing. Another common example is a biopsy result of “scant benign endometrium” in a patient with postmenopausal bleeding and thickened endometrial stripe on ultrasound. In both of these cases there is clear discordance between physical findings and the results of pathology sampling. A pathology report, in all of its black and white certitude, seems like the most reliable source of information. However, always trust your clinical judgment. If the clinical picture is suggesting something far worse than these limited, often random or blind samplings, I recommend repeated or more extensive sampling (for example, dilation and curettage). At the very least, schedule close follow-up with repeated sampling if the symptom or finding persists. The emphasis here is on scheduled follow-up, rather than “p.r.n.,” because a patient who was given a “normal” pathology result to explain her abnormal symptoms may not volunteer that those symptoms are persistent as she may feel that anything sinister was already ruled out. Make certain that you explain the potential for misdiagnosis as the reason for why you would like to see her back shortly to ensure the issue has resolved.

Biopsy vulvar lesions, minimize empiric treatment

Vulvar cancer is notoriously associated with delayed diagnosis. Unfortunately, it is commonplace for gynecologic oncologists to see women who have vulvar cancers that have been empirically treated, sometimes for months or years, with steroids or other topical agents. If a lesion on the vulva is characteristically benign in appearance (such as condyloma or lichen sclerosis), it may be reasonable to start empiric treatment. However, all patients who are treated without biopsy should be rescheduled for a planned follow-up appointment in 2-3 months. If the lesion/area remains unchanged, or worse, the lesion should be biopsied before proceeding with a change in therapy or continued therapy. Once again, don’t rely on patients to return for evaluation if the lesion doesn’t improve. Many patients assume that our first empiric diagnosis is “gospel,” and therefore may not return if the treatment doesn’t work. Meanwhile, providers may assume that patients will know that there is uncertainty in our interpretation and that they will know to report if the initial treatment didn’t work. These assumptions are the recipe for delayed diagnosis. If there is too great a burden on the patient to schedule a return visit because of social or financial reasons then the patient should have a biopsy prior to initiation of treatment. As a rule, empiric treatment is not a good strategy for patients without good access to follow-up.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at obnews@mdedge.com.

References

1. Sullivan S. et al Gynecol Oncol. 2017 Feb;144(2):294-8.

2. Perkins R .et al J Low Genit Tract Dis. 2020 Apr;24(2):102-31.

Over the next 2 months we will dedicate this column to some general tips and pearls from the perspective of a gynecologic oncologist to guide general obstetrician gynecologists in the workup and management of preinvasive or invasive gynecologic diseases. The goal of these recommendations is to minimize misdiagnosis or delayed diagnosis and avoid unnecessary or untimely referrals.

Perform biopsy, not Pap smears, on visible cervical and vaginal lesions

The purpose of the Pap smear is to screen asymptomatic patients for cervical dysplasia or microscopic invasive disease. Cytology is an unreliable diagnostic tool for visible, symptomatic lesions in large part because of sampling errors, and the lack of architectural information in cytologic versus histopathologic specimens. Invasive lesions can be mischaracterized as preinvasive on a Pap smear. This can result in delayed diagnosis and unnecessary diagnostic procedures. For example, if a visible, abnormal-appearing, cervical lesion is seen during a routine visit and a Pap smear is performed (rather than a biopsy of the mass), the patient may receive an incorrect preliminary diagnosis of “high-grade dysplasia, carcinoma in situ” as it can be difficult to distinguish invasive carcinoma from carcinoma in situ on cytology. If the patient and provider do not understand the limitations of Pap smears in diagnosing invasive cancers, they may be falsely reassured and possibly delay or abstain from follow-up for an excisional procedure. If she does return for the loop electrosurgical excision procedure (LEEP), there might still be unnecessary delays in making referrals and definitive treatment while waiting for results. Radical hysterectomy may not promptly follow because, if performed within 6 weeks of an excisional procedure, it is associated with a significantly higher risk for perioperative complication, and therefore, if the excisional procedure was unnecessary to begin with, there may be additional time lost that need not be.¹

Some clinicians avoid biopsy of visible lesions because they are concerned about bleeding complications that might arise in the office. Straightforward strategies to control bleeding are readily available in most gynecology offices, especially those already equipped for procedures such as LEEP and colposcopy. Prior to performing the biopsy, clinicians should ensure that they have supplies such as gauze sponges and ring forceps or packing forceps, silver nitrate, and ferric subsulfate solution (“Monsel’s solution”) close at hand. In the vast majority of cases, direct pressure for 5 minutes with gauze sponges and ferric subsulfate is highly effective at resolving most bleeding from a cervical or vaginal biopsy site. If this does not bring hemostasis, cautery devices or suture can be employed. If all else fails, be prepared to place vaginal packing (always with the insertion of a urinary Foley catheter to prevent urinary retention). In my experience, this is rarely needed.

Wherever possible, visible cervical or vaginal (or vulvar, see below) lesions should be biopsied for histopathology, sampling representative areas of the most concerning portion, in order to minimize misdiagnosis and expedite referral and definitive treatment. For necrotic-appearing lesions I recommend taking multiple samples of the tumor, as necrotic, nonviable tissue can prevent accurate diagnosis of a cancer. In general, Pap smears should be reserved as screening tests for asymptomatic women without visible pathology.
 

Don’t treat or refer low-grade dysplasia, even if persistent

Increasingly we are understanding that low-grade dysplasia of the lower genital tract (CIN I, VAIN I, VIN I) is less a precursor for cancer, and more a phenomenon of benign HPV-associated changes.² This HPV change may be chronically persistent, may require years of observation and serial Pap smears, and may be a general nuisance for the patient. However, current guidelines do not recommend intervention for low-grade dysplasia of the lower genital tract.² Interventions to resect these lesions can result in morbidity, including perineal pain, vaginal scarring, and cervical stenosis or insufficiency. Given the extremely low risk for progression to cancer, these morbidities do not outweigh any small potential benefit.

When I am conferring with patients who have chronic low-grade dysplasia I spend a great deal of time exploring their understanding of the diagnosis and its pathophysiology, their fears, and their expectation regarding “success” of treatment. I spend the time educating them that this is a sequela of chronic viral infection that will not be eradicated with local surgical excisions, that their cancer risk and need for surveillance would persist even if surgical intervention were offered, and that the side effects of treatment would outweigh any benefit from the small risk of cancer or high-grade dysplasia.

In summary, the treatment of choice for persistent low-grade dysplasia of the lower genital tract is comprehensive patient education, not surgical resection or referral to gynecologic oncology.
 

Repeat sampling if there’s a discordance between imaging and biopsy results

Delay in cancer diagnosis is one of the greatest concerns for front-line gynecology providers. One of the more modifiable strategies to avoid missed or delayed diagnosis is to ensure that there is concordance between clinical findings and testing results. Otherwise said: The results and findings should make sense in aggregate. An example was cited above in which a visible cervical mass demonstrated CIN III on cytologic testing. Another common example is a biopsy result of “scant benign endometrium” in a patient with postmenopausal bleeding and thickened endometrial stripe on ultrasound. In both of these cases there is clear discordance between physical findings and the results of pathology sampling. A pathology report, in all of its black and white certitude, seems like the most reliable source of information. However, always trust your clinical judgment. If the clinical picture is suggesting something far worse than these limited, often random or blind samplings, I recommend repeated or more extensive sampling (for example, dilation and curettage). At the very least, schedule close follow-up with repeated sampling if the symptom or finding persists. The emphasis here is on scheduled follow-up, rather than “p.r.n.,” because a patient who was given a “normal” pathology result to explain her abnormal symptoms may not volunteer that those symptoms are persistent as she may feel that anything sinister was already ruled out. Make certain that you explain the potential for misdiagnosis as the reason for why you would like to see her back shortly to ensure the issue has resolved.

Biopsy vulvar lesions, minimize empiric treatment

Vulvar cancer is notoriously associated with delayed diagnosis. Unfortunately, it is commonplace for gynecologic oncologists to see women who have vulvar cancers that have been empirically treated, sometimes for months or years, with steroids or other topical agents. If a lesion on the vulva is characteristically benign in appearance (such as condyloma or lichen sclerosis), it may be reasonable to start empiric treatment. However, all patients who are treated without biopsy should be rescheduled for a planned follow-up appointment in 2-3 months. If the lesion/area remains unchanged, or worse, the lesion should be biopsied before proceeding with a change in therapy or continued therapy. Once again, don’t rely on patients to return for evaluation if the lesion doesn’t improve. Many patients assume that our first empiric diagnosis is “gospel,” and therefore may not return if the treatment doesn’t work. Meanwhile, providers may assume that patients will know that there is uncertainty in our interpretation and that they will know to report if the initial treatment didn’t work. These assumptions are the recipe for delayed diagnosis. If there is too great a burden on the patient to schedule a return visit because of social or financial reasons then the patient should have a biopsy prior to initiation of treatment. As a rule, empiric treatment is not a good strategy for patients without good access to follow-up.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at obnews@mdedge.com.

References

1. Sullivan S. et al Gynecol Oncol. 2017 Feb;144(2):294-8.

2. Perkins R .et al J Low Genit Tract Dis. 2020 Apr;24(2):102-31.

Over the next 2 months we will dedicate this column to some general tips and pearls from the perspective of a gynecologic oncologist to guide general obstetrician gynecologists in the workup and management of preinvasive or invasive gynecologic diseases. The goal of these recommendations is to minimize misdiagnosis or delayed diagnosis and avoid unnecessary or untimely referrals.

Perform biopsy, not Pap smears, on visible cervical and vaginal lesions

The purpose of the Pap smear is to screen asymptomatic patients for cervical dysplasia or microscopic invasive disease. Cytology is an unreliable diagnostic tool for visible, symptomatic lesions in large part because of sampling errors, and the lack of architectural information in cytologic versus histopathologic specimens. Invasive lesions can be mischaracterized as preinvasive on a Pap smear. This can result in delayed diagnosis and unnecessary diagnostic procedures. For example, if a visible, abnormal-appearing, cervical lesion is seen during a routine visit and a Pap smear is performed (rather than a biopsy of the mass), the patient may receive an incorrect preliminary diagnosis of “high-grade dysplasia, carcinoma in situ” as it can be difficult to distinguish invasive carcinoma from carcinoma in situ on cytology. If the patient and provider do not understand the limitations of Pap smears in diagnosing invasive cancers, they may be falsely reassured and possibly delay or abstain from follow-up for an excisional procedure. If she does return for the loop electrosurgical excision procedure (LEEP), there might still be unnecessary delays in making referrals and definitive treatment while waiting for results. Radical hysterectomy may not promptly follow because, if performed within 6 weeks of an excisional procedure, it is associated with a significantly higher risk for perioperative complication, and therefore, if the excisional procedure was unnecessary to begin with, there may be additional time lost that need not be.¹

Some clinicians avoid biopsy of visible lesions because they are concerned about bleeding complications that might arise in the office. Straightforward strategies to control bleeding are readily available in most gynecology offices, especially those already equipped for procedures such as LEEP and colposcopy. Prior to performing the biopsy, clinicians should ensure that they have supplies such as gauze sponges and ring forceps or packing forceps, silver nitrate, and ferric subsulfate solution (“Monsel’s solution”) close at hand. In the vast majority of cases, direct pressure for 5 minutes with gauze sponges and ferric subsulfate is highly effective at resolving most bleeding from a cervical or vaginal biopsy site. If this does not bring hemostasis, cautery devices or suture can be employed. If all else fails, be prepared to place vaginal packing (always with the insertion of a urinary Foley catheter to prevent urinary retention). In my experience, this is rarely needed.

Wherever possible, visible cervical or vaginal (or vulvar, see below) lesions should be biopsied for histopathology, sampling representative areas of the most concerning portion, in order to minimize misdiagnosis and expedite referral and definitive treatment. For necrotic-appearing lesions I recommend taking multiple samples of the tumor, as necrotic, nonviable tissue can prevent accurate diagnosis of a cancer. In general, Pap smears should be reserved as screening tests for asymptomatic women without visible pathology.
 

Don’t treat or refer low-grade dysplasia, even if persistent

Increasingly we are understanding that low-grade dysplasia of the lower genital tract (CIN I, VAIN I, VIN I) is less a precursor for cancer, and more a phenomenon of benign HPV-associated changes.² This HPV change may be chronically persistent, may require years of observation and serial Pap smears, and may be a general nuisance for the patient. However, current guidelines do not recommend intervention for low-grade dysplasia of the lower genital tract.² Interventions to resect these lesions can result in morbidity, including perineal pain, vaginal scarring, and cervical stenosis or insufficiency. Given the extremely low risk for progression to cancer, these morbidities do not outweigh any small potential benefit.

When I am conferring with patients who have chronic low-grade dysplasia I spend a great deal of time exploring their understanding of the diagnosis and its pathophysiology, their fears, and their expectation regarding “success” of treatment. I spend the time educating them that this is a sequela of chronic viral infection that will not be eradicated with local surgical excisions, that their cancer risk and need for surveillance would persist even if surgical intervention were offered, and that the side effects of treatment would outweigh any benefit from the small risk of cancer or high-grade dysplasia.

In summary, the treatment of choice for persistent low-grade dysplasia of the lower genital tract is comprehensive patient education, not surgical resection or referral to gynecologic oncology.
 

Repeat sampling if there’s a discordance between imaging and biopsy results

Delay in cancer diagnosis is one of the greatest concerns for front-line gynecology providers. One of the more modifiable strategies to avoid missed or delayed diagnosis is to ensure that there is concordance between clinical findings and testing results. Otherwise said: The results and findings should make sense in aggregate. An example was cited above in which a visible cervical mass demonstrated CIN III on cytologic testing. Another common example is a biopsy result of “scant benign endometrium” in a patient with postmenopausal bleeding and thickened endometrial stripe on ultrasound. In both of these cases there is clear discordance between physical findings and the results of pathology sampling. A pathology report, in all of its black and white certitude, seems like the most reliable source of information. However, always trust your clinical judgment. If the clinical picture is suggesting something far worse than these limited, often random or blind samplings, I recommend repeated or more extensive sampling (for example, dilation and curettage). At the very least, schedule close follow-up with repeated sampling if the symptom or finding persists. The emphasis here is on scheduled follow-up, rather than “p.r.n.,” because a patient who was given a “normal” pathology result to explain her abnormal symptoms may not volunteer that those symptoms are persistent as she may feel that anything sinister was already ruled out. Make certain that you explain the potential for misdiagnosis as the reason for why you would like to see her back shortly to ensure the issue has resolved.

Biopsy vulvar lesions, minimize empiric treatment

Vulvar cancer is notoriously associated with delayed diagnosis. Unfortunately, it is commonplace for gynecologic oncologists to see women who have vulvar cancers that have been empirically treated, sometimes for months or years, with steroids or other topical agents. If a lesion on the vulva is characteristically benign in appearance (such as condyloma or lichen sclerosis), it may be reasonable to start empiric treatment. However, all patients who are treated without biopsy should be rescheduled for a planned follow-up appointment in 2-3 months. If the lesion/area remains unchanged, or worse, the lesion should be biopsied before proceeding with a change in therapy or continued therapy. Once again, don’t rely on patients to return for evaluation if the lesion doesn’t improve. Many patients assume that our first empiric diagnosis is “gospel,” and therefore may not return if the treatment doesn’t work. Meanwhile, providers may assume that patients will know that there is uncertainty in our interpretation and that they will know to report if the initial treatment didn’t work. These assumptions are the recipe for delayed diagnosis. If there is too great a burden on the patient to schedule a return visit because of social or financial reasons then the patient should have a biopsy prior to initiation of treatment. As a rule, empiric treatment is not a good strategy for patients without good access to follow-up.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at obnews@mdedge.com.

References

1. Sullivan S. et al Gynecol Oncol. 2017 Feb;144(2):294-8.

2. Perkins R .et al J Low Genit Tract Dis. 2020 Apr;24(2):102-31.

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

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

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

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

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

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

Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.

Background

Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.

The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.

Adapted from Int J Gynecol Obstet. 2011;113:3-13.

Fibroids and fertility

Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).

Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
 

Treatment options – medical

Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).

When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).

Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.

Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
 

Treatment options – surgical

Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.

Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
 

Noninvasive treatment modalities

Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.

High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).

Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
 

Conclusion

The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at obnews@mdedge.com.

Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.

Background

Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.

The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.

Adapted from Int J Gynecol Obstet. 2011;113:3-13.

Fibroids and fertility

Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).

Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
 

Treatment options – medical

Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).

When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).

Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.

Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
 

Treatment options – surgical

Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.

Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
 

Noninvasive treatment modalities

Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.

High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).

Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
 

Conclusion

The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at obnews@mdedge.com.

Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.

Background

Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.

The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.

Adapted from Int J Gynecol Obstet. 2011;113:3-13.

Fibroids and fertility

Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).

Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
 

Treatment options – medical

Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).

When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).

Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.

Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
 

Treatment options – surgical

Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.

Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
 

Noninvasive treatment modalities

Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.

High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).

Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
 

Conclusion

The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at obnews@mdedge.com.

The risk of in-hospital complications and poor birth outcomes were greater in pregnant women with current or historical cancer diagnoses, new research suggests.

The study, published in Mayo Clinic Proceedings, found that women with current and historical cancer diagnoses had an increased risk of death, kidney injury, and stroke during delivery hospitalizations, compared with those with no cancer. When it came to delivery outcomes, this group also had a higher risk for preterm birth and postpartum hemorrhage. Those with a current cancer diagnoses had a 1.7-fold increase in odds for a preterm birth, compared with women without cancer.

“Our study found that metastases increased the odds of mortality, cesarean delivery, preterm birth, and stillbirth,” the researchers noted. “Coupled with previous research reporting that pregnant women are more likely to be diagnosed with advanced disease, this implies that pregnant women with newly diagnosed cancer have poor prognoses.”

However, although women with prior cancer had increased odds of mortality, the researchers said it was not statistically significant.

“The study really did not show an increase of mortality [for women with prior cancer diagnosis],” said Justin Chura, MD, a specialist in gynecologic oncology who was not involved in the study. “And the reason might be because there is not or the reason might be because it’s such a rare event. You would need 100 million births to assess that. So I would actually use caution in that interpretation.”

Researchers analyzed more than 43 million delivery hospitalizations of women with or without current or historical cancer diagnoses between January 2004 and December 2014. They found that the most common cancer diagnoses were hematologic, thyroid, cervical, skin, and breast.

Of the five most common cancers, the prevalence of all maternal complications and negative delivery outcomes was the highest among women with hematologic cancers. They were more likely to experience peripartum cardiomyopathy, acute kidney injury, and arrhythmia, compared with other cancers. Postpartum hemorrhage, maternal mortality, and placental abruption was also more likely to occur in those with this type of cancer.

“I was surprised that it was the hematologic cancers that were worse when they did it by cancer type,” said Dr. Chura, who is the chief of surgery and the director of gynecologic oncology and robotic surgery at the Cancer Treatment Centers of America’s Eastern Regional Medical Center in Philadelphia. “I think this is a useful bit of information for counseling our patients and also to identify the cohort with the highest risk.”

The findings also suggested that those with skin cancer had the highest odds for stroke, while women with cervical and breast cancers were more likely to experience acute kidney injury and preterm birth.

Dr. Chura said cancer treatments can have an impact on a woman’s health when she’s giving birth. For example, if a woman is diagnosed with cervical cancer, doctors may perform a cone biopsy on her where they remove a large portion of the cervix and still leave them with the ability to conceive and become pregnant. However, those patients are left with a higher risk of a preterm delivery.

For women with a hematologic cancer like non-Hodgkin’s lymphoma, chest radiation may cause some subsequent damage to their heart muscles “and now the stress of pregnancy puts more demand on the heart that can lead to cardiac complications for that patient,” Dr. Chura said.

“There are potential long-term effects from radiation and chemotherapy,” Dr. Chura said.

Previous studies have shown that chemotherapy may affect pregnancy and delivery. A 2019 study published in the Journal of Cancer also found that 59 pregnant women with cancer had increased mortality compared with those without the long-term illness. Meanwhile, another 2018 study published in Cancer found that women who conceived less than a year after starting chemotherapy had higher risks of preterm birth in comparison with those who conceived more than a year after starting chemotherapy. The study also found that cancer survivors who conceived more than a year after finishing chemotherapy with or without radiation had no higher risk of a preterm birth than those without cancer.

Dr. Chura said the new study could force doctors to think about the long-term effects of their cancer therapies and make them more apt to think about how to make cancer therapy less toxic with less long-term health consequences, while still curing patients.

“Most oncologists, when dealing with younger patients, are very focused on curing the cancer at hand, but not necessarily thinking 5 or 10 years down the road,” Dr. Chura said. “[This study] could help inform or at least make us aware of the long-term consequences of our cancer therapies.”

Dr. Chura had no relevant financial disclosures.

The risk of in-hospital complications and poor birth outcomes were greater in pregnant women with current or historical cancer diagnoses, new research suggests.

The study, published in Mayo Clinic Proceedings, found that women with current and historical cancer diagnoses had an increased risk of death, kidney injury, and stroke during delivery hospitalizations, compared with those with no cancer. When it came to delivery outcomes, this group also had a higher risk for preterm birth and postpartum hemorrhage. Those with a current cancer diagnoses had a 1.7-fold increase in odds for a preterm birth, compared with women without cancer.

“Our study found that metastases increased the odds of mortality, cesarean delivery, preterm birth, and stillbirth,” the researchers noted. “Coupled with previous research reporting that pregnant women are more likely to be diagnosed with advanced disease, this implies that pregnant women with newly diagnosed cancer have poor prognoses.”

However, although women with prior cancer had increased odds of mortality, the researchers said it was not statistically significant.

“The study really did not show an increase of mortality [for women with prior cancer diagnosis],” said Justin Chura, MD, a specialist in gynecologic oncology who was not involved in the study. “And the reason might be because there is not or the reason might be because it’s such a rare event. You would need 100 million births to assess that. So I would actually use caution in that interpretation.”

Researchers analyzed more than 43 million delivery hospitalizations of women with or without current or historical cancer diagnoses between January 2004 and December 2014. They found that the most common cancer diagnoses were hematologic, thyroid, cervical, skin, and breast.

Of the five most common cancers, the prevalence of all maternal complications and negative delivery outcomes was the highest among women with hematologic cancers. They were more likely to experience peripartum cardiomyopathy, acute kidney injury, and arrhythmia, compared with other cancers. Postpartum hemorrhage, maternal mortality, and placental abruption was also more likely to occur in those with this type of cancer.

“I was surprised that it was the hematologic cancers that were worse when they did it by cancer type,” said Dr. Chura, who is the chief of surgery and the director of gynecologic oncology and robotic surgery at the Cancer Treatment Centers of America’s Eastern Regional Medical Center in Philadelphia. “I think this is a useful bit of information for counseling our patients and also to identify the cohort with the highest risk.”

The findings also suggested that those with skin cancer had the highest odds for stroke, while women with cervical and breast cancers were more likely to experience acute kidney injury and preterm birth.

Dr. Chura said cancer treatments can have an impact on a woman’s health when she’s giving birth. For example, if a woman is diagnosed with cervical cancer, doctors may perform a cone biopsy on her where they remove a large portion of the cervix and still leave them with the ability to conceive and become pregnant. However, those patients are left with a higher risk of a preterm delivery.

For women with a hematologic cancer like non-Hodgkin’s lymphoma, chest radiation may cause some subsequent damage to their heart muscles “and now the stress of pregnancy puts more demand on the heart that can lead to cardiac complications for that patient,” Dr. Chura said.

“There are potential long-term effects from radiation and chemotherapy,” Dr. Chura said.

Previous studies have shown that chemotherapy may affect pregnancy and delivery. A 2019 study published in the Journal of Cancer also found that 59 pregnant women with cancer had increased mortality compared with those without the long-term illness. Meanwhile, another 2018 study published in Cancer found that women who conceived less than a year after starting chemotherapy had higher risks of preterm birth in comparison with those who conceived more than a year after starting chemotherapy. The study also found that cancer survivors who conceived more than a year after finishing chemotherapy with or without radiation had no higher risk of a preterm birth than those without cancer.

Dr. Chura said the new study could force doctors to think about the long-term effects of their cancer therapies and make them more apt to think about how to make cancer therapy less toxic with less long-term health consequences, while still curing patients.

“Most oncologists, when dealing with younger patients, are very focused on curing the cancer at hand, but not necessarily thinking 5 or 10 years down the road,” Dr. Chura said. “[This study] could help inform or at least make us aware of the long-term consequences of our cancer therapies.”

Dr. Chura had no relevant financial disclosures.

The risk of in-hospital complications and poor birth outcomes were greater in pregnant women with current or historical cancer diagnoses, new research suggests.

The study, published in Mayo Clinic Proceedings, found that women with current and historical cancer diagnoses had an increased risk of death, kidney injury, and stroke during delivery hospitalizations, compared with those with no cancer. When it came to delivery outcomes, this group also had a higher risk for preterm birth and postpartum hemorrhage. Those with a current cancer diagnoses had a 1.7-fold increase in odds for a preterm birth, compared with women without cancer.

“Our study found that metastases increased the odds of mortality, cesarean delivery, preterm birth, and stillbirth,” the researchers noted. “Coupled with previous research reporting that pregnant women are more likely to be diagnosed with advanced disease, this implies that pregnant women with newly diagnosed cancer have poor prognoses.”

However, although women with prior cancer had increased odds of mortality, the researchers said it was not statistically significant.

“The study really did not show an increase of mortality [for women with prior cancer diagnosis],” said Justin Chura, MD, a specialist in gynecologic oncology who was not involved in the study. “And the reason might be because there is not or the reason might be because it’s such a rare event. You would need 100 million births to assess that. So I would actually use caution in that interpretation.”

Researchers analyzed more than 43 million delivery hospitalizations of women with or without current or historical cancer diagnoses between January 2004 and December 2014. They found that the most common cancer diagnoses were hematologic, thyroid, cervical, skin, and breast.

Of the five most common cancers, the prevalence of all maternal complications and negative delivery outcomes was the highest among women with hematologic cancers. They were more likely to experience peripartum cardiomyopathy, acute kidney injury, and arrhythmia, compared with other cancers. Postpartum hemorrhage, maternal mortality, and placental abruption was also more likely to occur in those with this type of cancer.

“I was surprised that it was the hematologic cancers that were worse when they did it by cancer type,” said Dr. Chura, who is the chief of surgery and the director of gynecologic oncology and robotic surgery at the Cancer Treatment Centers of America’s Eastern Regional Medical Center in Philadelphia. “I think this is a useful bit of information for counseling our patients and also to identify the cohort with the highest risk.”

The findings also suggested that those with skin cancer had the highest odds for stroke, while women with cervical and breast cancers were more likely to experience acute kidney injury and preterm birth.

Dr. Chura said cancer treatments can have an impact on a woman’s health when she’s giving birth. For example, if a woman is diagnosed with cervical cancer, doctors may perform a cone biopsy on her where they remove a large portion of the cervix and still leave them with the ability to conceive and become pregnant. However, those patients are left with a higher risk of a preterm delivery.

For women with a hematologic cancer like non-Hodgkin’s lymphoma, chest radiation may cause some subsequent damage to their heart muscles “and now the stress of pregnancy puts more demand on the heart that can lead to cardiac complications for that patient,” Dr. Chura said.

“There are potential long-term effects from radiation and chemotherapy,” Dr. Chura said.

Previous studies have shown that chemotherapy may affect pregnancy and delivery. A 2019 study published in the Journal of Cancer also found that 59 pregnant women with cancer had increased mortality compared with those without the long-term illness. Meanwhile, another 2018 study published in Cancer found that women who conceived less than a year after starting chemotherapy had higher risks of preterm birth in comparison with those who conceived more than a year after starting chemotherapy. The study also found that cancer survivors who conceived more than a year after finishing chemotherapy with or without radiation had no higher risk of a preterm birth than those without cancer.

Dr. Chura said the new study could force doctors to think about the long-term effects of their cancer therapies and make them more apt to think about how to make cancer therapy less toxic with less long-term health consequences, while still curing patients.

“Most oncologists, when dealing with younger patients, are very focused on curing the cancer at hand, but not necessarily thinking 5 or 10 years down the road,” Dr. Chura said. “[This study] could help inform or at least make us aware of the long-term consequences of our cancer therapies.”

Dr. Chura had no relevant financial disclosures.

I dream of alien abductions

There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?

Engin Akyurt/Pixabay

Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.

In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.

So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
 

Follow your heart: Drink more coffee

It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.

s-photo/iStockphoto.com

In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.

The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.

What they found, after the 4-year follow up, was nothing short of myth busting.

“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”

There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.

We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
 

Bored? Feeling down? Don’t play Candy Crush

Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?

pxfuel

Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.

Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.

The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
 

Hiccups and vaccine refusal

Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?

But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.

Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)

Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)

And now, back to the news.

Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]

djedj/Pixabay

Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.

His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)

I dream of alien abductions

There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?

Engin Akyurt/Pixabay

Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.

In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.

So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
 

Follow your heart: Drink more coffee

It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.

s-photo/iStockphoto.com

In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.

The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.

What they found, after the 4-year follow up, was nothing short of myth busting.

“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”

There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.

We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
 

Bored? Feeling down? Don’t play Candy Crush

Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?

pxfuel

Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.

Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.

The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
 

Hiccups and vaccine refusal

Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?

But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.

Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)

Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)

And now, back to the news.

Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]

djedj/Pixabay

Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.

His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)

I dream of alien abductions

There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?

Engin Akyurt/Pixabay

Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.

In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.

So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
 

Follow your heart: Drink more coffee

It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.

s-photo/iStockphoto.com

In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.

The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.

What they found, after the 4-year follow up, was nothing short of myth busting.

“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”

There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.

We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
 

Bored? Feeling down? Don’t play Candy Crush

Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?

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Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.

Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.

The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
 

Hiccups and vaccine refusal

Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?

But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.

Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)

Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)

And now, back to the news.

Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]

djedj/Pixabay

Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.

His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.