MDedge ObGyn

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

Tosha Rogers, MD, is a one-woman HIV prevention evangelist. For nearly a decade now, the Atlanta-based ob/gyn has been on a mission to increase her gynecological colleagues’ awareness and prescribing of the oral HIV prevention pill. At the same time, she’s been tracking the development of a flexible vaginal ring loaded with a month’s worth of the HIV prevention medication dapivirine. That, she thought, would fit easily into women’s lives and into the toolbox of methods women already use to prevent pregnancy.

But now she’s not sure when – or if – the ring will find its way to her patients. In December, the ring’s maker, the International Partnership for Microbicides (IPM), pulled its application for FDA approval for the pre-exposure prophylaxis (PrEP) ring. Now, one year after the World Health Organization recommended the ring for member nations, there appears to be no path forward in the United States for either the dapivirine-only ring or an approach Dr. Rogers said would change the game: a vaginal ring that supplies both contraception and HIV prevention.

“It would take things to a whole other level,” she said. “It sucks that this happened, and I do think it was not anything medical. I think it was everything political.”

That leaves cisgender women – especially the Black and Latinx women who make up the vast majority of women who acquire HIV every year – with two HIV prevention options. One is the daily pill, first approved in 2012. It’s now generic but previously sold as Truvada by Gilead Sciences. The other is monthly injectable cabotegravir long-acting (Apretude). Another HIV prevention pill, tenofovir alafenamide/emtricitabine (Descovy), is approved for gay men and transgender women but not cisgender women.
 

Vagina-specific protection from HIV

The WHO recommendation for the vaginal ring was followed last July by a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for women in low- and middle-income countries outside the European Union.

The flexible silicone ring, similar to the hormonal NuvaRing contraceptive, works by slowly releasing the antiretroviral dapivirine directly into the vaginal canal, thereby protecting women who might be exposed to the virus through vaginal sex only. Because the medicine stays where it’s delivered and doesn’t circulate through the body, it has been found to be extremely safe with few adverse events.

However, in initial studies, the ring was found to be just 27% effective overall. Later studies, where scientists divided women by how much drug was missing from the ring – a proxy for use – found that higher use was associated with higher protection (as much as 54%). By comparison, Truvada has been found to be up to 99% effective when used daily, though it can take up to 21 days to be available in the vagina in high enough concentrations to protect women from vaginal exposure. And the HIV prevention shot was found to be 90% more effective than that in a recent trial of the two methods conducted by the HIV Prevention Trials Network.

This, and an orientation away from topical HIV prevention drugs and toward systemic options, led the National Institute of Allergy and Infectious Diseases (NIAID) to discontinue funding for such projects under its Microbicide Trials Network.

“Clearly you want to counsel women to use the highest efficacy method, and that is part of our label,” Zeda Rosenberg, ScD, IPM’s founder and chief executive officer, told this news organization. “Women should not choose the ring if they can and will use oral PrEP, and I would argue it should be the same thing for [cabotegravir shots]. But if they can’t or don’t want to – and we know that especially many young women don’t want to use systemic methods – then the dapivirine ring is a great option.”

Still, Dr. Rosenberg said that the gap in efficacy, the relatively small number of women affected by HIV in the U.S. compared with gay and bisexual men, and the emergence of products like the HIV prevention shot cabotegravir, made it “very unlikely” that FDA regulators would approve the ring. And rather than be “distracted” by the FDA process, Dr. Rosenberg said IPM chose to concentrate on the countries where the ring has already been approved or where women make up the vast majority of people affected by HIV.

Zimbabwe publicly announced it has approved the ring, and three other countries may have approved it, according to Dr. Rosenberg. She declined to name them, saying they had requested silence while they formulate their new HIV prevention guidelines. Aside from Zimbabwe, the other countries where women participated in the ring clinical trials were South Africa, Malawi, and Uganda.

“The U.S. population ... has widespread access to oral PrEP, which is unlike countries in Africa, and which would have widespread access to injectable cabotegravir,” she said. “The U.S. FDA may not see choice in the same way that African women and African activists and advocates see the need for choice.”

But women’s rates of accessing HIV prevention medications in the U.S. continues to be frustratingly low. At the end of 2018, just 7% of women who could benefit from HIV prevention drugs were taking them, according to Centers for Disease Control and Prevention data.

New CDC guidelines recommend clinicians talk to every sexually active adult and adolescent about HIV prevention medications at least once and prescribe it to anyone who asks for it, whether or not they understand their patients’ HIV risks. However, research continues to show that clinicians struggle with willingness to prescribe PrEP to Black women, and the American College of Obstetrics and Gynecology’s committee opinion on managing women using HIV prevention drugs has not been updated to reflect the new guidelines. And while the HIV prevention shot is approved for women and its maker ViiV Healthcare is already initiating postmarket studies of the ring in key populations including women, there are lots of things that need to line up in order for clinicians to be willing to stock it and prescribe it to women.

From where Dázon Dixon Diallo, executive director of the nonprofit SisterLove, sits, the decision to withdraw the ring from FDA consideration and the FDA’s seeming argument that the epidemiology in the U.S. doesn’t warrant the ring’s approval is a slap in the face to the Black women who have led the movement to end HIV in the U.S. for decades.

“No matter how you slice it, we’re talking about Black women, and then we’re talking about brown women,” said Ms. Diallo. “The value [they place on us] from a government standpoint, from a political standpoint, from a public health standpoint is just woeful. It’s woeful and it’s disrespectful and it’s insulting and I’m sick of it.”
 

‘America sneezes and Africa catches a cold’

When she first heard the decision to pull the ring from FDA consideration, Yvette Raphael, the South Africa-based executive director of Advocates for the Prevention of HIV in Africa, started asking, “What can we do to help our sisters in America get this ring?” And then she started worrying about other women in her own country and those nearby.

“The FDA plays a big role,” she said. “You know, America sneezes and Africa catches a cold.”

She worries that IPM’s decision to withdraw the ring from FDA consideration will signal to regulators in other countries either (a) that they should not approve it or (b) in countries where it’s already been approved but guidelines have not been issued, that they won’t invest money in rolling it out to women in those countries – especially now with the U.S. approval of the prevention shot. In much of Africa, ministries of health prefer to provide injectable contraception, often giving women few or no other options. But women, she said, think about more than administration of the drug. They look at if it’s an easier option for them to manage.

“This is a long journey, an emotional one too, for women in South Africa, because the idea of a microbicide is one of the ideas that came directly from women in South Africa,” she said. “[The jab] can be seen as a solution to all. We can just give jabs to all the women. And after all, we know that women don’t adhere, so we can just grab them.”

Dr. Rosenberg pointed to the positive opinion from the EMA as another “rigorous review” process that she said ought to equally influence ministries of health in countries where women tested the ring. And she pointed to the WHO statement released last month, the same day as IPM’s announcement that it was withdrawing the ring from FDA considerations, recommitting the ring as a good option in sub-Saharan Africa: “The U.S. FDA decision is not based on any new or additional data on efficacy and safety,” it stated. “WHO will continue to support countries as they consider whether to include the [dapivirine vaginal ring]. WHO recognizes that country decisionmaking will vary based on their context and that women’s voices remain central to discussions about their prevention choices.”
 

Dual action ring on the horizon, but not in U.S.

What this means, though, is that the next step in the ring’s development – the combination dapivirine ring with contraceptive levonorgestrel (used in the Mirena intrauterine device) – may not come to the U.S., at least for a long while.

“It’s not out of the question,” Dr. Rosenberg said of conducting HIV/pregnancy prevention ring trials in the U.S. “But without the approval of the dapivirine-only ring by FDA, I imagine they would want to see new efficacy data on dapivirine. That is a very difficult hill to climb. There would have to be an active control group [using oral PrEP or injectable cabotegravir], and it would be very difficult for the dapivirine ring to be able to go head-to-head for either noninferiority and certainly for superiority.”

The study would need to be quite large to get enough results to prove anything, and IPM is a research organization, not a large pharmaceutical company with deep enough pockets to fund that, she said. Raising those funds “would be difficult.”

In addition to NIAID discontinuing its funding for the Microbicides Trials Network, a new 5-year, $85 million research collaboration through USAID hasn’t slated any money to fund trials of the combination HIV prevention and contraceptive ring, according to Dr. Rosenberg.

But that doesn’t mean avenues for its development are closed. NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently funding a phase 1/2 trial of the combination ring, and IPM continues to receive funding from research agencies in Germany, the Netherlands, Denmark, and Ireland. And this means, she said, that the E.U. – not the U.S. – is where they would seek approval for a combination ring first.

That leaves Ms. Rafael and Ms. Diallo debating how to work together to push the FDA – and maybe IPM – to reconsider the ring. For instance, Ms. Diallo suggested that instead of seeking an indication for all women, the FDA might consider the ring for women with very high risk of HIV, such as sex workers or women with HIV positive partners not on treatment. And she said that this has to be bigger than HIV prevention. It has to be about the ways in which women’s health issues in general lag at the FDA. For instance, she pointed to the movement to get contraceptive pills available over the counter, fights against FDA rulings on hormone replacement therapy, and fights for emergency contraception.

In the meantime, ob/gyn Dr. Rogers is expecting access to the ring to follow a similar path as the copper IUD, which migrated to the U.S. from Europe, where it has been among the most popular contraceptive methods for women.

“Contrary to what we may think, we are not innovators, especially for something like this,” she said. “Once we see it is working and doing a good job – that women in Europe love it – then someone here is going to pick it up and make it as if it’s the greatest thing. But for now, I think we’re going to have to take a back seat to Europe.”

Ms. Diallo reports receiving fees from Johnson & Johnson, ViiV Healthcare, and Gilead Sciences. Dr. Rosenberg and Dr. Rogers have disclosed no relevant financial relationships.

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

A new, highly contagious subvariant of Omicron has emerged, which some have begun calling “son of Omicron,” but public health officials say it’s too soon to tell what kind of real threat, if any, this new strain will present.

In the meantime, it’s worth watching BA.2, the World Health Organization said. The subvariant has been identified across at least 40 countries, including three cases reported in Houston and several in Washington state.

BA.2 accounts for only a small minority of reported cases so far, including 5% in India, 4% of those in the United Kingdom, and 2% each of cases in Sweden and Singapore.

The one exception is Denmark, a country with robust genetic sequencing abilities, where estimates range from 50% to 81% of cases.

The news throws a little more uncertainty into an already uncertain situation, including how close the world might be to a less life-altering infectious disease.

For example, the world is at an ideal point for a new variant to emerge, WHO Director General Tedros Adhanom Ghebreyesus, PhD, said during a Jan. 24 meeting of the WHO executive board. He also said it’s too early to call an “end game” to the pandemic.

Similarly, Anthony S. Fauci, MD, said on Jan. 19 that it remained “an open question” whether the Omicron variant could hasten endemic COVID-19, a situation where the virus still circulates but is much less disruptive to everyday life.
 

No Pi for you

This could be the first time a coronavirus subvariant rises to the level of a household name, or – if previous variants of the moment have shown us – it could recede from the spotlight.

For example, a lot of focus on the potential of the Mu variant to wreak havoc fizzled out a few weeks after the WHO listed it as a variant of interest on Aug. 30.

Subvariants can feature mutations and other small differences but are not distinct enough from an existing strain to be called a variant on their own and be named after the next letter in the Greek alphabet. That’s why BA.2 is not called the “Pi variant.”

Predicting what’s next for the coronavirus has puzzled many experts throughout the pandemic. That is why many public health officials wait for the WHO to officially designate a strain as a variant of interest or variant of concern before taking action.

At the moment with BA.2, it seems close monitoring is warranted.

Because it’s too early to call, expert predictions about BA.2 vary widely, from worry to cautious optimism.

For example, early data indicates that BA.2 could be more worrisome than original Omicron, Eric Feigl-Ding, ScD, an epidemiologist and health economist, said on Twitter.

Information from Denmark seems to show BA.2 either has “much faster transmission or it evades immunity even more,” he said.

The same day, Jan. 23, Dr. Feigl-Ding tweeted that other data shows the subvariant can spread twice as fast as Omicron, which was already much more contagious than previous versions of the virus.

At the same time, other experts appear less concerned. Robert Garry, PhD, a virologist at Tulane University, New Orleans, told the Washington Post that there is no reason to think BA.2 will be any worse than the original Omicron strain.

So which expert predictions will come closer to BA.2’s potential? For now, it’s just a watch-and-see situation.

For updated information, the website outbreak.info tracks BA.2’s average daily and cumulative prevalence in the United States and in other locations.

Also, if and when WHO experts decide to elevate BA.2 to a variant of interest or a variant of concern, it will be noted on its coronavirus variant tracking website.

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

A new, highly contagious subvariant of Omicron has emerged, which some have begun calling “son of Omicron,” but public health officials say it’s too soon to tell what kind of real threat, if any, this new strain will present.

In the meantime, it’s worth watching BA.2, the World Health Organization said. The subvariant has been identified across at least 40 countries, including three cases reported in Houston and several in Washington state.

BA.2 accounts for only a small minority of reported cases so far, including 5% in India, 4% of those in the United Kingdom, and 2% each of cases in Sweden and Singapore.

The one exception is Denmark, a country with robust genetic sequencing abilities, where estimates range from 50% to 81% of cases.

The news throws a little more uncertainty into an already uncertain situation, including how close the world might be to a less life-altering infectious disease.

For example, the world is at an ideal point for a new variant to emerge, WHO Director General Tedros Adhanom Ghebreyesus, PhD, said during a Jan. 24 meeting of the WHO executive board. He also said it’s too early to call an “end game” to the pandemic.

Similarly, Anthony S. Fauci, MD, said on Jan. 19 that it remained “an open question” whether the Omicron variant could hasten endemic COVID-19, a situation where the virus still circulates but is much less disruptive to everyday life.
 

No Pi for you

This could be the first time a coronavirus subvariant rises to the level of a household name, or – if previous variants of the moment have shown us – it could recede from the spotlight.

For example, a lot of focus on the potential of the Mu variant to wreak havoc fizzled out a few weeks after the WHO listed it as a variant of interest on Aug. 30.

Subvariants can feature mutations and other small differences but are not distinct enough from an existing strain to be called a variant on their own and be named after the next letter in the Greek alphabet. That’s why BA.2 is not called the “Pi variant.”

Predicting what’s next for the coronavirus has puzzled many experts throughout the pandemic. That is why many public health officials wait for the WHO to officially designate a strain as a variant of interest or variant of concern before taking action.

At the moment with BA.2, it seems close monitoring is warranted.

Because it’s too early to call, expert predictions about BA.2 vary widely, from worry to cautious optimism.

For example, early data indicates that BA.2 could be more worrisome than original Omicron, Eric Feigl-Ding, ScD, an epidemiologist and health economist, said on Twitter.

Information from Denmark seems to show BA.2 either has “much faster transmission or it evades immunity even more,” he said.

The same day, Jan. 23, Dr. Feigl-Ding tweeted that other data shows the subvariant can spread twice as fast as Omicron, which was already much more contagious than previous versions of the virus.

At the same time, other experts appear less concerned. Robert Garry, PhD, a virologist at Tulane University, New Orleans, told the Washington Post that there is no reason to think BA.2 will be any worse than the original Omicron strain.

So which expert predictions will come closer to BA.2’s potential? For now, it’s just a watch-and-see situation.

For updated information, the website outbreak.info tracks BA.2’s average daily and cumulative prevalence in the United States and in other locations.

Also, if and when WHO experts decide to elevate BA.2 to a variant of interest or a variant of concern, it will be noted on its coronavirus variant tracking website.

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

A new, highly contagious subvariant of Omicron has emerged, which some have begun calling “son of Omicron,” but public health officials say it’s too soon to tell what kind of real threat, if any, this new strain will present.

In the meantime, it’s worth watching BA.2, the World Health Organization said. The subvariant has been identified across at least 40 countries, including three cases reported in Houston and several in Washington state.

BA.2 accounts for only a small minority of reported cases so far, including 5% in India, 4% of those in the United Kingdom, and 2% each of cases in Sweden and Singapore.

The one exception is Denmark, a country with robust genetic sequencing abilities, where estimates range from 50% to 81% of cases.

The news throws a little more uncertainty into an already uncertain situation, including how close the world might be to a less life-altering infectious disease.

For example, the world is at an ideal point for a new variant to emerge, WHO Director General Tedros Adhanom Ghebreyesus, PhD, said during a Jan. 24 meeting of the WHO executive board. He also said it’s too early to call an “end game” to the pandemic.

Similarly, Anthony S. Fauci, MD, said on Jan. 19 that it remained “an open question” whether the Omicron variant could hasten endemic COVID-19, a situation where the virus still circulates but is much less disruptive to everyday life.
 

No Pi for you

This could be the first time a coronavirus subvariant rises to the level of a household name, or – if previous variants of the moment have shown us – it could recede from the spotlight.

For example, a lot of focus on the potential of the Mu variant to wreak havoc fizzled out a few weeks after the WHO listed it as a variant of interest on Aug. 30.

Subvariants can feature mutations and other small differences but are not distinct enough from an existing strain to be called a variant on their own and be named after the next letter in the Greek alphabet. That’s why BA.2 is not called the “Pi variant.”

Predicting what’s next for the coronavirus has puzzled many experts throughout the pandemic. That is why many public health officials wait for the WHO to officially designate a strain as a variant of interest or variant of concern before taking action.

At the moment with BA.2, it seems close monitoring is warranted.

Because it’s too early to call, expert predictions about BA.2 vary widely, from worry to cautious optimism.

For example, early data indicates that BA.2 could be more worrisome than original Omicron, Eric Feigl-Ding, ScD, an epidemiologist and health economist, said on Twitter.

Information from Denmark seems to show BA.2 either has “much faster transmission or it evades immunity even more,” he said.

The same day, Jan. 23, Dr. Feigl-Ding tweeted that other data shows the subvariant can spread twice as fast as Omicron, which was already much more contagious than previous versions of the virus.

At the same time, other experts appear less concerned. Robert Garry, PhD, a virologist at Tulane University, New Orleans, told the Washington Post that there is no reason to think BA.2 will be any worse than the original Omicron strain.

So which expert predictions will come closer to BA.2’s potential? For now, it’s just a watch-and-see situation.

For updated information, the website outbreak.info tracks BA.2’s average daily and cumulative prevalence in the United States and in other locations.

Also, if and when WHO experts decide to elevate BA.2 to a variant of interest or a variant of concern, it will be noted on its coronavirus variant tracking website.

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

A digital algorithm using 24 patient characteristics identifies far more women who are likely to develop a postpartum hemorrhage than currently used tools to predict the risk for bleeding after delivery, according to a study published in the Journal of the American Medical Informatics Association.

About 1 in 10 of the roughly 700 pregnancy-related deaths in the United States are caused by postpartum hemorrhage, according to the U.S. Centers for Disease Control and Prevention. These deaths disproportionately occur among Black women, for whom studies show the risk of dying from a postpartum hemorrhage is fivefold greater than that of White women.

“Postpartum hemorrhage is a preventable medical emergency but remains the leading cause of maternal mortality globally,” the study’s senior author Li Li, MD, senior vice president of clinical informatics at Sema4, a company that uses artificial intelligence and machine learning to develop data-based clinical tools, told this news organization. “Early intervention is critical for reducing postpartum hemorrhage morbidity and mortality.”
 

Porous predictors

Existing tools for risk prediction are not particularly effective, Dr. Li said. For example, the American College of Obstetricians and Gynecologists’ (ACOG) Safe Motherhood Initiative offers checklists of clinical characteristics to classify women as low, medium, or high risk. However, 40% of the women classified as low risk based on this type of tool experience a hemorrhage.

ACOG also recommends quantifying blood loss during delivery or immediately after to identify women who are hemorrhaging, because imprecise estimates from clinicians may delay urgently needed care. Yet many hospitals have not implemented methods for measuring bleeding, said Dr. Li, who also is an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York.

To develop a more precise way of identifying women at risk, Dr. Li and colleagues turned to artificial intelligence technology to create a “digital phenotype” based on approximately 72,000 births in the Mount Sinai Health System.

The digital tool retrospectively identified about 6,600 cases of postpartum hemorrhage, about 3.8 times the roughly 1,700 cases that would have been predicted based on methods that estimate blood loss. A blinded physician review of a subset of 45 patient charts – including 26 patients who experienced a hemorrhage, 11 who didn’t, and 6 with unclear outcomes – found that the digital approach was 89% percent accurate at identifying cases, whereas blood loss–based methods were accurate 67% of the time.

Several of the 24 characteristics included in the model appear in other risk predictors, including whether a woman has had a previous cesarean delivery or prior postdelivery bleeding and whether she has anemia or related blood disorders. Among the rest were risk factors that have been identified in the literature, including maternal blood pressure, time from admission to delivery, and average pulse during hospitalization. Five more features were new: red blood cell count and distribution width, mean corpuscular hemoglobin, absolute neutrophil count, and white blood cell count.

“These [new] values are easily obtainable from standard blood draws in the hospital but are not currently used in clinical practice to estimate postpartum hemorrhage risk,” Dr. Li said.

In a related retrospective study, Dr. Li and her colleagues used the new tool to classify women into high, low, or medium risk categories. They found that 28% of the women the algorithm classified as high risk experienced a postpartum hemorrhage compared with 15% to 19% of the women classified as high risk by standard predictive tools. They also identified potential “inflection points” where changes in vital signs may suggest a substantial increase in risk. For example, women whose median blood pressure during labor and delivery was above 132 mm Hg had an 11% average increase in their risk for bleeding. 

By more precisely identifying women at risk, the new method “could be used to pre-emptively allocate resources that can ultimately reduce postpartum hemorrhage morbidity and mortality,” Dr. Li said. Sema4 is launching a prospective clinical trial to further assess the algorithm, she added.  
 

Finding the continuum of risk

Holly Ende, MD, an obstetric anesthesiologist at Vanderbilt University Medical Center, Nashville, Tenn., said approaches that leverage electronic health records to identify women at risk for hemorrhage have many advantages over currently used tools.

“Machine learning models or statistical models are able to take into account many more risk factors and weigh each of those risk factors based on how much they contribute to risk,” Dr. Ende, who was not involved in the new studies, told this news organization. “We can stratify women more on a continuum.”

But digital approaches have potential downsides.

“Machine learning algorithms can be developed in such a way that perpetuates racial bias, and it’s important to be aware of potential biases in coded algorithms,” Dr. Li said. To help reduce such bias, they used a database that included a racially and ethnically diverse patient population, but she acknowledged that additional research is needed.

Dr. Ende, the coauthor of a commentary in Obstetrics & Gynecology on risk assessment for postpartum hemorrhage, said algorithm developers must be sensitive to pre-existing disparities in health care that may affect the data they use to build the software.

She pointed to uterine atony – a known risk factor for hemorrhage – as an example. In her own research, she and her colleagues identified women with atony by searching their medical records for medications used to treat the condition. But when they ran their model, Black women were less likely to develop uterine atony, which the team knew wasn’t true in the real world. They traced the problem to an existing disparity in obstetric care: Black women with uterine atony were less likely than women of other races to receive medications for the condition.

“People need to be cognizant as they are developing these types of prediction models and be extremely careful to avoid perpetuating any disparities in care,” Dr. Ende cautioned. On the other hand, if carefully developed, these tools might also help reduce disparities in health care by standardizing risk stratification and clinical practices, she said.

In addition to independent validation of data-based risk prediction tools, Dr. Ende said ensuring that clinicians are properly trained to use these tools is crucial.

“Implementation may be the biggest limitation,” she said.

Dr. Ende and Dr. Li have disclosed no relevant financial relationships.

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

A digital algorithm using 24 patient characteristics identifies far more women who are likely to develop a postpartum hemorrhage than currently used tools to predict the risk for bleeding after delivery, according to a study published in the Journal of the American Medical Informatics Association.

About 1 in 10 of the roughly 700 pregnancy-related deaths in the United States are caused by postpartum hemorrhage, according to the U.S. Centers for Disease Control and Prevention. These deaths disproportionately occur among Black women, for whom studies show the risk of dying from a postpartum hemorrhage is fivefold greater than that of White women.

“Postpartum hemorrhage is a preventable medical emergency but remains the leading cause of maternal mortality globally,” the study’s senior author Li Li, MD, senior vice president of clinical informatics at Sema4, a company that uses artificial intelligence and machine learning to develop data-based clinical tools, told this news organization. “Early intervention is critical for reducing postpartum hemorrhage morbidity and mortality.”
 

Porous predictors

Existing tools for risk prediction are not particularly effective, Dr. Li said. For example, the American College of Obstetricians and Gynecologists’ (ACOG) Safe Motherhood Initiative offers checklists of clinical characteristics to classify women as low, medium, or high risk. However, 40% of the women classified as low risk based on this type of tool experience a hemorrhage.

ACOG also recommends quantifying blood loss during delivery or immediately after to identify women who are hemorrhaging, because imprecise estimates from clinicians may delay urgently needed care. Yet many hospitals have not implemented methods for measuring bleeding, said Dr. Li, who also is an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York.

To develop a more precise way of identifying women at risk, Dr. Li and colleagues turned to artificial intelligence technology to create a “digital phenotype” based on approximately 72,000 births in the Mount Sinai Health System.

The digital tool retrospectively identified about 6,600 cases of postpartum hemorrhage, about 3.8 times the roughly 1,700 cases that would have been predicted based on methods that estimate blood loss. A blinded physician review of a subset of 45 patient charts – including 26 patients who experienced a hemorrhage, 11 who didn’t, and 6 with unclear outcomes – found that the digital approach was 89% percent accurate at identifying cases, whereas blood loss–based methods were accurate 67% of the time.

Several of the 24 characteristics included in the model appear in other risk predictors, including whether a woman has had a previous cesarean delivery or prior postdelivery bleeding and whether she has anemia or related blood disorders. Among the rest were risk factors that have been identified in the literature, including maternal blood pressure, time from admission to delivery, and average pulse during hospitalization. Five more features were new: red blood cell count and distribution width, mean corpuscular hemoglobin, absolute neutrophil count, and white blood cell count.

“These [new] values are easily obtainable from standard blood draws in the hospital but are not currently used in clinical practice to estimate postpartum hemorrhage risk,” Dr. Li said.

In a related retrospective study, Dr. Li and her colleagues used the new tool to classify women into high, low, or medium risk categories. They found that 28% of the women the algorithm classified as high risk experienced a postpartum hemorrhage compared with 15% to 19% of the women classified as high risk by standard predictive tools. They also identified potential “inflection points” where changes in vital signs may suggest a substantial increase in risk. For example, women whose median blood pressure during labor and delivery was above 132 mm Hg had an 11% average increase in their risk for bleeding. 

By more precisely identifying women at risk, the new method “could be used to pre-emptively allocate resources that can ultimately reduce postpartum hemorrhage morbidity and mortality,” Dr. Li said. Sema4 is launching a prospective clinical trial to further assess the algorithm, she added.  
 

Finding the continuum of risk

Holly Ende, MD, an obstetric anesthesiologist at Vanderbilt University Medical Center, Nashville, Tenn., said approaches that leverage electronic health records to identify women at risk for hemorrhage have many advantages over currently used tools.

“Machine learning models or statistical models are able to take into account many more risk factors and weigh each of those risk factors based on how much they contribute to risk,” Dr. Ende, who was not involved in the new studies, told this news organization. “We can stratify women more on a continuum.”

But digital approaches have potential downsides.

“Machine learning algorithms can be developed in such a way that perpetuates racial bias, and it’s important to be aware of potential biases in coded algorithms,” Dr. Li said. To help reduce such bias, they used a database that included a racially and ethnically diverse patient population, but she acknowledged that additional research is needed.

Dr. Ende, the coauthor of a commentary in Obstetrics & Gynecology on risk assessment for postpartum hemorrhage, said algorithm developers must be sensitive to pre-existing disparities in health care that may affect the data they use to build the software.

She pointed to uterine atony – a known risk factor for hemorrhage – as an example. In her own research, she and her colleagues identified women with atony by searching their medical records for medications used to treat the condition. But when they ran their model, Black women were less likely to develop uterine atony, which the team knew wasn’t true in the real world. They traced the problem to an existing disparity in obstetric care: Black women with uterine atony were less likely than women of other races to receive medications for the condition.

“People need to be cognizant as they are developing these types of prediction models and be extremely careful to avoid perpetuating any disparities in care,” Dr. Ende cautioned. On the other hand, if carefully developed, these tools might also help reduce disparities in health care by standardizing risk stratification and clinical practices, she said.

In addition to independent validation of data-based risk prediction tools, Dr. Ende said ensuring that clinicians are properly trained to use these tools is crucial.

“Implementation may be the biggest limitation,” she said.

Dr. Ende and Dr. Li have disclosed no relevant financial relationships.

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

A digital algorithm using 24 patient characteristics identifies far more women who are likely to develop a postpartum hemorrhage than currently used tools to predict the risk for bleeding after delivery, according to a study published in the Journal of the American Medical Informatics Association.

About 1 in 10 of the roughly 700 pregnancy-related deaths in the United States are caused by postpartum hemorrhage, according to the U.S. Centers for Disease Control and Prevention. These deaths disproportionately occur among Black women, for whom studies show the risk of dying from a postpartum hemorrhage is fivefold greater than that of White women.

“Postpartum hemorrhage is a preventable medical emergency but remains the leading cause of maternal mortality globally,” the study’s senior author Li Li, MD, senior vice president of clinical informatics at Sema4, a company that uses artificial intelligence and machine learning to develop data-based clinical tools, told this news organization. “Early intervention is critical for reducing postpartum hemorrhage morbidity and mortality.”
 

Porous predictors

Existing tools for risk prediction are not particularly effective, Dr. Li said. For example, the American College of Obstetricians and Gynecologists’ (ACOG) Safe Motherhood Initiative offers checklists of clinical characteristics to classify women as low, medium, or high risk. However, 40% of the women classified as low risk based on this type of tool experience a hemorrhage.

ACOG also recommends quantifying blood loss during delivery or immediately after to identify women who are hemorrhaging, because imprecise estimates from clinicians may delay urgently needed care. Yet many hospitals have not implemented methods for measuring bleeding, said Dr. Li, who also is an assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York.

To develop a more precise way of identifying women at risk, Dr. Li and colleagues turned to artificial intelligence technology to create a “digital phenotype” based on approximately 72,000 births in the Mount Sinai Health System.

The digital tool retrospectively identified about 6,600 cases of postpartum hemorrhage, about 3.8 times the roughly 1,700 cases that would have been predicted based on methods that estimate blood loss. A blinded physician review of a subset of 45 patient charts – including 26 patients who experienced a hemorrhage, 11 who didn’t, and 6 with unclear outcomes – found that the digital approach was 89% percent accurate at identifying cases, whereas blood loss–based methods were accurate 67% of the time.

Several of the 24 characteristics included in the model appear in other risk predictors, including whether a woman has had a previous cesarean delivery or prior postdelivery bleeding and whether she has anemia or related blood disorders. Among the rest were risk factors that have been identified in the literature, including maternal blood pressure, time from admission to delivery, and average pulse during hospitalization. Five more features were new: red blood cell count and distribution width, mean corpuscular hemoglobin, absolute neutrophil count, and white blood cell count.

“These [new] values are easily obtainable from standard blood draws in the hospital but are not currently used in clinical practice to estimate postpartum hemorrhage risk,” Dr. Li said.

In a related retrospective study, Dr. Li and her colleagues used the new tool to classify women into high, low, or medium risk categories. They found that 28% of the women the algorithm classified as high risk experienced a postpartum hemorrhage compared with 15% to 19% of the women classified as high risk by standard predictive tools. They also identified potential “inflection points” where changes in vital signs may suggest a substantial increase in risk. For example, women whose median blood pressure during labor and delivery was above 132 mm Hg had an 11% average increase in their risk for bleeding. 

By more precisely identifying women at risk, the new method “could be used to pre-emptively allocate resources that can ultimately reduce postpartum hemorrhage morbidity and mortality,” Dr. Li said. Sema4 is launching a prospective clinical trial to further assess the algorithm, she added.  
 

Finding the continuum of risk

Holly Ende, MD, an obstetric anesthesiologist at Vanderbilt University Medical Center, Nashville, Tenn., said approaches that leverage electronic health records to identify women at risk for hemorrhage have many advantages over currently used tools.

“Machine learning models or statistical models are able to take into account many more risk factors and weigh each of those risk factors based on how much they contribute to risk,” Dr. Ende, who was not involved in the new studies, told this news organization. “We can stratify women more on a continuum.”

But digital approaches have potential downsides.

“Machine learning algorithms can be developed in such a way that perpetuates racial bias, and it’s important to be aware of potential biases in coded algorithms,” Dr. Li said. To help reduce such bias, they used a database that included a racially and ethnically diverse patient population, but she acknowledged that additional research is needed.

Dr. Ende, the coauthor of a commentary in Obstetrics & Gynecology on risk assessment for postpartum hemorrhage, said algorithm developers must be sensitive to pre-existing disparities in health care that may affect the data they use to build the software.

She pointed to uterine atony – a known risk factor for hemorrhage – as an example. In her own research, she and her colleagues identified women with atony by searching their medical records for medications used to treat the condition. But when they ran their model, Black women were less likely to develop uterine atony, which the team knew wasn’t true in the real world. They traced the problem to an existing disparity in obstetric care: Black women with uterine atony were less likely than women of other races to receive medications for the condition.

“People need to be cognizant as they are developing these types of prediction models and be extremely careful to avoid perpetuating any disparities in care,” Dr. Ende cautioned. On the other hand, if carefully developed, these tools might also help reduce disparities in health care by standardizing risk stratification and clinical practices, she said.

In addition to independent validation of data-based risk prediction tools, Dr. Ende said ensuring that clinicians are properly trained to use these tools is crucial.

“Implementation may be the biggest limitation,” she said.

Dr. Ende and Dr. Li have disclosed no relevant financial relationships.

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

Two years ago, I argued that independent care from nurse practitioners (NPs) and physician assistants (PAs) would not have ill effects on health outcomes. To the surprise of no one, NPs and PAs embraced the argument; physicians clobbered it.

My case had three pegs: One was that medicine isn’t rocket science and clinicians control a lot less than we think we do. The second peg was that technology levels the playing field of clinical care. High-sensitivity troponin assays, for instance, make missing MI a lot less likely. The third peg was empirical: Studies have found little difference in MD versus non–MD-led care. Looking back, I now see empiricism as the weakest part of the argument because the studies had so many limitations.

I update this viewpoint now because health care is increasingly delivered by NPs and PAs. And there are two concerning trends regarding NP education and experience. First is that nurses are turning to advanced practitioner training earlier in their careers – without gathering much bedside experience. And these training programs are increasingly likely to be online, with minimal hands-on clinical tutoring. 

Education and experience pop in my head often. Not every day, but many days I think back to my lucky 7 years in Indiana learning under the supervision of master clinicians – at a time when trainees were allowed the leeway to make decisions ... and mistakes. Then, when I joined private practice, I continued to learn from experienced practitioners.

It would be foolish to argue that training and experience aren’t important.

But here’s the thing: I still don’t see average health outcomes declining as a result of the rise in NPs and PAs. And even if I did, it wouldn’t matter. The rise in nonphysician care will not be undone, at least any time soon.

I will make three points: First, I will bolster two of my old arguments as to why we shouldn’t be worried about non-MD clinicians, then I will propose some ideas to increase confidence in NP and PA care.
 

Health care does not equal health

On the matter of how much clinicians affect outcomes, a recently published randomized controlled trial performed in India found that subsidizing insurance care led to increased utilization of hospital services but had no significant effect on health outcomes. This follows the RAND and Oregon Health Insurance studies in the United States, which largely reported similar results.

It’s about the delta

Logos trumps pathos. Sure, my physician colleagues can tell scary anecdotes of bad outcomes caused by an inexperienced NP or PA. I would counter that by saying I have sat on our hospital’s peer review committee for 2 decades, including the era before NPs or PAs were practicing, and I have plenty of stories of physician errors. These include, of course, my own errors.

Logos: We must consider the difference between non–MD-led care and MD-led care.

My arguments from 2020 remain relevant today. Most medical problems are not engineering puzzles. Many, perhaps most, patients fall into an easy protocol – say, chest pain, dyspnea, or atrial fibrillation. With basic training, a motivated serious person quickly gains skill in recognizing and treating everyday problems.

And just 2 years on, technology further levels the playing field. Consider radiology in 2022 – it’s easy to take for granted the speed of the CT scan, the fidelity of the MRI, and the easy access to both in the U.S. hospital system. Less experienced clinicians have never had more tools to assist with diagnostics and therapeutics.

The expansion of team-based care has also mitigated the effects of inexperience. It took Americans longer than Canadians to figure out how helpful pharmacists could be. Pharmacists in my hospital now help us dose complicated medicines and protect us against prescribing errors.

Then there is the immediate access to online information. Gone are the days when you had to memorize long-QT syndromes. Book knowledge – that I spent years acquiring – now comes in seconds. The other day an NP corrected me. I asked, Are you sure? Boom, she took out her phone and showed me the evidence.

In sum, if it were even possible to measure the clinical competence of care from NP and PA versus physicians, there would be two bell-shaped curves with a tremendous amount of overlap. And that overlap would steadily increase as a given NP or PA gathered experience. (The NP in our electrophysiology division has more than 25 years’ experience in heart rhythm care, and it is common for colleagues to call her before one of us docs. Rightly so.)
 

Three basic proposals regarding NP and PA care

To ensure quality of care, I have three proposals.

It has always seemed strange to me that an NP or PA can flip from one field to another without a period of training. I can’t just change practice from electrophysiology to dermatology without doing a residency. But NPs and PAs can.

My first proposal would be that NPs and PAs spend a substantial period of training in a field before practice – a legit apprenticeship. The duration of this period is a matter of debate, but it ought to be standardized.

My second proposal is that, if physicians are required to pass certification exams, so should NPs. (PAs have an exam every 10 years.) The exam should be the same as (or very similar to) the physician exam, and it should be specific to their field of practice.

While I have argued (and still feel) that the American Board of Internal Medicine brand of certification is dubious, the fact remains that physicians must maintain proficiency in their field. Requiring NPs and PAs to do the same would help foster specialization. And while I can’t cite empirical evidence, specialization seems super-important. We have NPs at my hospital who have been in the same area for years, and they exude clinical competence.

Finally, I have come to believe that the best way for nearly any clinician to practice medicine is as part of a team. (The exception being primary care in rural areas where there are clinician shortages.)

On the matter of team care, I’ve practiced for a long time, but nearly every day I run situations by a colleague; often this person is an NP. The economist Friedrich Hayek proposed that dispersed knowledge always outpaces the wisdom of any individual. That notion pertains well to the increasing complexities and specialization of modern medical practice.

A person who commits to learning one area of medicine, enjoys helping people, asks often for help, and has the support of colleagues is set up to be a successful clinician – whether the letters after their name are APRN, PA, DO, or MD.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky. He did not report any relevant financial disclosures. A version of this article first appeared on Medscape.com.

Two years ago, I argued that independent care from nurse practitioners (NPs) and physician assistants (PAs) would not have ill effects on health outcomes. To the surprise of no one, NPs and PAs embraced the argument; physicians clobbered it.

My case had three pegs: One was that medicine isn’t rocket science and clinicians control a lot less than we think we do. The second peg was that technology levels the playing field of clinical care. High-sensitivity troponin assays, for instance, make missing MI a lot less likely. The third peg was empirical: Studies have found little difference in MD versus non–MD-led care. Looking back, I now see empiricism as the weakest part of the argument because the studies had so many limitations.

I update this viewpoint now because health care is increasingly delivered by NPs and PAs. And there are two concerning trends regarding NP education and experience. First is that nurses are turning to advanced practitioner training earlier in their careers – without gathering much bedside experience. And these training programs are increasingly likely to be online, with minimal hands-on clinical tutoring. 

Education and experience pop in my head often. Not every day, but many days I think back to my lucky 7 years in Indiana learning under the supervision of master clinicians – at a time when trainees were allowed the leeway to make decisions ... and mistakes. Then, when I joined private practice, I continued to learn from experienced practitioners.

It would be foolish to argue that training and experience aren’t important.

But here’s the thing: I still don’t see average health outcomes declining as a result of the rise in NPs and PAs. And even if I did, it wouldn’t matter. The rise in nonphysician care will not be undone, at least any time soon.

I will make three points: First, I will bolster two of my old arguments as to why we shouldn’t be worried about non-MD clinicians, then I will propose some ideas to increase confidence in NP and PA care.
 

Health care does not equal health

On the matter of how much clinicians affect outcomes, a recently published randomized controlled trial performed in India found that subsidizing insurance care led to increased utilization of hospital services but had no significant effect on health outcomes. This follows the RAND and Oregon Health Insurance studies in the United States, which largely reported similar results.

It’s about the delta

Logos trumps pathos. Sure, my physician colleagues can tell scary anecdotes of bad outcomes caused by an inexperienced NP or PA. I would counter that by saying I have sat on our hospital’s peer review committee for 2 decades, including the era before NPs or PAs were practicing, and I have plenty of stories of physician errors. These include, of course, my own errors.

Logos: We must consider the difference between non–MD-led care and MD-led care.

My arguments from 2020 remain relevant today. Most medical problems are not engineering puzzles. Many, perhaps most, patients fall into an easy protocol – say, chest pain, dyspnea, or atrial fibrillation. With basic training, a motivated serious person quickly gains skill in recognizing and treating everyday problems.

And just 2 years on, technology further levels the playing field. Consider radiology in 2022 – it’s easy to take for granted the speed of the CT scan, the fidelity of the MRI, and the easy access to both in the U.S. hospital system. Less experienced clinicians have never had more tools to assist with diagnostics and therapeutics.

The expansion of team-based care has also mitigated the effects of inexperience. It took Americans longer than Canadians to figure out how helpful pharmacists could be. Pharmacists in my hospital now help us dose complicated medicines and protect us against prescribing errors.

Then there is the immediate access to online information. Gone are the days when you had to memorize long-QT syndromes. Book knowledge – that I spent years acquiring – now comes in seconds. The other day an NP corrected me. I asked, Are you sure? Boom, she took out her phone and showed me the evidence.

In sum, if it were even possible to measure the clinical competence of care from NP and PA versus physicians, there would be two bell-shaped curves with a tremendous amount of overlap. And that overlap would steadily increase as a given NP or PA gathered experience. (The NP in our electrophysiology division has more than 25 years’ experience in heart rhythm care, and it is common for colleagues to call her before one of us docs. Rightly so.)
 

Three basic proposals regarding NP and PA care

To ensure quality of care, I have three proposals.

It has always seemed strange to me that an NP or PA can flip from one field to another without a period of training. I can’t just change practice from electrophysiology to dermatology without doing a residency. But NPs and PAs can.

My first proposal would be that NPs and PAs spend a substantial period of training in a field before practice – a legit apprenticeship. The duration of this period is a matter of debate, but it ought to be standardized.

My second proposal is that, if physicians are required to pass certification exams, so should NPs. (PAs have an exam every 10 years.) The exam should be the same as (or very similar to) the physician exam, and it should be specific to their field of practice.

While I have argued (and still feel) that the American Board of Internal Medicine brand of certification is dubious, the fact remains that physicians must maintain proficiency in their field. Requiring NPs and PAs to do the same would help foster specialization. And while I can’t cite empirical evidence, specialization seems super-important. We have NPs at my hospital who have been in the same area for years, and they exude clinical competence.

Finally, I have come to believe that the best way for nearly any clinician to practice medicine is as part of a team. (The exception being primary care in rural areas where there are clinician shortages.)

On the matter of team care, I’ve practiced for a long time, but nearly every day I run situations by a colleague; often this person is an NP. The economist Friedrich Hayek proposed that dispersed knowledge always outpaces the wisdom of any individual. That notion pertains well to the increasing complexities and specialization of modern medical practice.

A person who commits to learning one area of medicine, enjoys helping people, asks often for help, and has the support of colleagues is set up to be a successful clinician – whether the letters after their name are APRN, PA, DO, or MD.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky. He did not report any relevant financial disclosures. A version of this article first appeared on Medscape.com.

Two years ago, I argued that independent care from nurse practitioners (NPs) and physician assistants (PAs) would not have ill effects on health outcomes. To the surprise of no one, NPs and PAs embraced the argument; physicians clobbered it.

My case had three pegs: One was that medicine isn’t rocket science and clinicians control a lot less than we think we do. The second peg was that technology levels the playing field of clinical care. High-sensitivity troponin assays, for instance, make missing MI a lot less likely. The third peg was empirical: Studies have found little difference in MD versus non–MD-led care. Looking back, I now see empiricism as the weakest part of the argument because the studies had so many limitations.

I update this viewpoint now because health care is increasingly delivered by NPs and PAs. And there are two concerning trends regarding NP education and experience. First is that nurses are turning to advanced practitioner training earlier in their careers – without gathering much bedside experience. And these training programs are increasingly likely to be online, with minimal hands-on clinical tutoring. 

Education and experience pop in my head often. Not every day, but many days I think back to my lucky 7 years in Indiana learning under the supervision of master clinicians – at a time when trainees were allowed the leeway to make decisions ... and mistakes. Then, when I joined private practice, I continued to learn from experienced practitioners.

It would be foolish to argue that training and experience aren’t important.

But here’s the thing: I still don’t see average health outcomes declining as a result of the rise in NPs and PAs. And even if I did, it wouldn’t matter. The rise in nonphysician care will not be undone, at least any time soon.

I will make three points: First, I will bolster two of my old arguments as to why we shouldn’t be worried about non-MD clinicians, then I will propose some ideas to increase confidence in NP and PA care.
 

Health care does not equal health

On the matter of how much clinicians affect outcomes, a recently published randomized controlled trial performed in India found that subsidizing insurance care led to increased utilization of hospital services but had no significant effect on health outcomes. This follows the RAND and Oregon Health Insurance studies in the United States, which largely reported similar results.

It’s about the delta

Logos trumps pathos. Sure, my physician colleagues can tell scary anecdotes of bad outcomes caused by an inexperienced NP or PA. I would counter that by saying I have sat on our hospital’s peer review committee for 2 decades, including the era before NPs or PAs were practicing, and I have plenty of stories of physician errors. These include, of course, my own errors.

Logos: We must consider the difference between non–MD-led care and MD-led care.

My arguments from 2020 remain relevant today. Most medical problems are not engineering puzzles. Many, perhaps most, patients fall into an easy protocol – say, chest pain, dyspnea, or atrial fibrillation. With basic training, a motivated serious person quickly gains skill in recognizing and treating everyday problems.

And just 2 years on, technology further levels the playing field. Consider radiology in 2022 – it’s easy to take for granted the speed of the CT scan, the fidelity of the MRI, and the easy access to both in the U.S. hospital system. Less experienced clinicians have never had more tools to assist with diagnostics and therapeutics.

The expansion of team-based care has also mitigated the effects of inexperience. It took Americans longer than Canadians to figure out how helpful pharmacists could be. Pharmacists in my hospital now help us dose complicated medicines and protect us against prescribing errors.

Then there is the immediate access to online information. Gone are the days when you had to memorize long-QT syndromes. Book knowledge – that I spent years acquiring – now comes in seconds. The other day an NP corrected me. I asked, Are you sure? Boom, she took out her phone and showed me the evidence.

In sum, if it were even possible to measure the clinical competence of care from NP and PA versus physicians, there would be two bell-shaped curves with a tremendous amount of overlap. And that overlap would steadily increase as a given NP or PA gathered experience. (The NP in our electrophysiology division has more than 25 years’ experience in heart rhythm care, and it is common for colleagues to call her before one of us docs. Rightly so.)
 

Three basic proposals regarding NP and PA care

To ensure quality of care, I have three proposals.

It has always seemed strange to me that an NP or PA can flip from one field to another without a period of training. I can’t just change practice from electrophysiology to dermatology without doing a residency. But NPs and PAs can.

My first proposal would be that NPs and PAs spend a substantial period of training in a field before practice – a legit apprenticeship. The duration of this period is a matter of debate, but it ought to be standardized.

My second proposal is that, if physicians are required to pass certification exams, so should NPs. (PAs have an exam every 10 years.) The exam should be the same as (or very similar to) the physician exam, and it should be specific to their field of practice.

While I have argued (and still feel) that the American Board of Internal Medicine brand of certification is dubious, the fact remains that physicians must maintain proficiency in their field. Requiring NPs and PAs to do the same would help foster specialization. And while I can’t cite empirical evidence, specialization seems super-important. We have NPs at my hospital who have been in the same area for years, and they exude clinical competence.

Finally, I have come to believe that the best way for nearly any clinician to practice medicine is as part of a team. (The exception being primary care in rural areas where there are clinician shortages.)

On the matter of team care, I’ve practiced for a long time, but nearly every day I run situations by a colleague; often this person is an NP. The economist Friedrich Hayek proposed that dispersed knowledge always outpaces the wisdom of any individual. That notion pertains well to the increasing complexities and specialization of modern medical practice.

A person who commits to learning one area of medicine, enjoys helping people, asks often for help, and has the support of colleagues is set up to be a successful clinician – whether the letters after their name are APRN, PA, DO, or MD.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky. He did not report any relevant financial disclosures. A version of this article first appeared on Medscape.com.

Doctors who are unhappy with low insurance payments may be able to level the playing field and negotiate better rates in their contracts, say experts in physician-payer contracts.

Many doctors sign long-term agreements and then forget about them, says Marcia Brauchler, president and founder of Physicians’ Ally, Littleton, Colorado, a health care consulting company. “The average doctor is trying to run a practice on 2010 rates because they haven’t touched their insurance contracts for 10 years,” she says.

Payers also make a lot of money by adopting dozens of unilateral policy and procedure changes every year that they know physicians are too busy to read. They are counting on the fact that few doctors will understand what the policy changes are and that even fewer will contest them, says Greg Brodek, JD, chair of the health law practice group and head of the managed care litigation practice at Duane Morris, who represents doctors in disputes with payers.

These experts say doctors can push back on one-sided payer contracts and negotiate changes. Mr. Brodek says some practices have more leverage than others to influence payers – if they are larger, in a specialty that the payer needs in its network, or located in a remote area where the payer has limited options.

Here are seven key areas to pay attention to:

1. Long-term contracts. Most doctors sign multiyear “evergreen” contracts that renew automatically every year. This allows insurers to continue to pay doctors the same rate for years.

To avoid this, doctors should negotiate new rates when their agreements renew or, if they prefer, ask that a cost-of-living adjustment be included in the multiyear contract that applies to subsequent years, says Ms. Brauchler.

2. Fee schedules. Payers will “whitewash” what they’re paying you by saying it’s 100% of the payer fee schedule. When it comes to Medicare, they may be paying you a lot less, says Ms. Brauchler.

“My biggest takeaway is to compare the CPT codes of the payer’s fee schedule against what Medicare allows. For example, for CPT code 99213, a 15-minute established office visit, if Medicare pays you $100 and Aetna pays you $75.00, you’re getting 75% of Medicare,” says Ms. Brauchler. To avoid this, doctors should ask that the contract state that reimbursement be made according to Medicare’s medical policies rather than the payer’s.

3. Audits. Commercial payers will claim they have a contractual right to conduct pre- and post-payment audits of physicians’ claims that can result in reduced payments. The contract only states that if doctors correctly submit claims, they will get paid, not that they will have to go through extra steps, which is a breach of their agreement, says Mr. Brodek.

In his experience, 90% of payers back down when asked to provide the contractual basis to conduct these audits. “Or, they take the position that it’s not in the contract but that they have a policy.”

4. Contract amendments versus policies and procedures. This is a huge area that needs to be clarified in contracts and monitored by providers throughout their relationships with payers. Contracts have three elements: the parties, the services provided, and the payment. Changing any one of those terms requires an amendment and advance written notice that has to be delivered to the other party in a certain way, such as by overnight delivery, says Mr. Brodek.

In addition, both parties have to sign that they agree to an amendment. “But, that’s too cumbersome and complicated for payers who have decided to adopt policies instead. These are unilateral changes made with no advance notice given, since the payer typically posts the change on its website,” says Mr. Brodek.

5. Recoupment efforts. Payers will review claims after they’re paid and contact the doctor saying they found a mistake, such as inappropriate coding. They will claim that the doctor now owes them a large sum of money based on a percentage of claims reviewed. “They typically send the doctor a letter that ends with, ‘If you do not pay this amount within 30 days, we will offset the amount due against future payments that we would otherwise make to you,’” says Mr. Brodek.

He recommends that contracts include the doctors’ right to contest an audit so the “payer doesn’t have the unilateral right to disregard the initial coding that the doctor appropriately assigned to the claim and recoup the money anyway,” says Mr. Brodek.

6. Medical network rentals and products. Most contracts say that payers can rent out their medical networks to other health plans, such as HMOs, and that the clinicians agree to comply with all of their policies and procedures. The agreement may also cover the products of other plans.

“The problem is that physicians are not given information about the other plans, including their terms and conditions for getting paid,” says Mr. Brodek. If a problem with payment arises, they have no written agreement with that plan, which makes it harder to enforce.

“That’s why we recommend that doctors negotiate agreements that only cover the main payer. Most of the time, the payer is amenable to putting that language in the contract,” he says.

7. Payer products. In the past several years, a typical contract has included appendices that list the payer’s products, such as Medicare, workers compensation, auto insurance liability, or health care exchange products. Many clinicians don’t realize they can pick the plans they want to participate in by accepting or opting out, says Mr. Brodek.

“We advise clients to limit the contract to what you want covered and to make informed decisions, because some products have low fees set by the states, such as workers compensation and health care exchanges,” says Mr. Brodek.

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

Doctors who are unhappy with low insurance payments may be able to level the playing field and negotiate better rates in their contracts, say experts in physician-payer contracts.

Many doctors sign long-term agreements and then forget about them, says Marcia Brauchler, president and founder of Physicians’ Ally, Littleton, Colorado, a health care consulting company. “The average doctor is trying to run a practice on 2010 rates because they haven’t touched their insurance contracts for 10 years,” she says.

Payers also make a lot of money by adopting dozens of unilateral policy and procedure changes every year that they know physicians are too busy to read. They are counting on the fact that few doctors will understand what the policy changes are and that even fewer will contest them, says Greg Brodek, JD, chair of the health law practice group and head of the managed care litigation practice at Duane Morris, who represents doctors in disputes with payers.

These experts say doctors can push back on one-sided payer contracts and negotiate changes. Mr. Brodek says some practices have more leverage than others to influence payers – if they are larger, in a specialty that the payer needs in its network, or located in a remote area where the payer has limited options.

Here are seven key areas to pay attention to:

1. Long-term contracts. Most doctors sign multiyear “evergreen” contracts that renew automatically every year. This allows insurers to continue to pay doctors the same rate for years.

To avoid this, doctors should negotiate new rates when their agreements renew or, if they prefer, ask that a cost-of-living adjustment be included in the multiyear contract that applies to subsequent years, says Ms. Brauchler.

2. Fee schedules. Payers will “whitewash” what they’re paying you by saying it’s 100% of the payer fee schedule. When it comes to Medicare, they may be paying you a lot less, says Ms. Brauchler.

“My biggest takeaway is to compare the CPT codes of the payer’s fee schedule against what Medicare allows. For example, for CPT code 99213, a 15-minute established office visit, if Medicare pays you $100 and Aetna pays you $75.00, you’re getting 75% of Medicare,” says Ms. Brauchler. To avoid this, doctors should ask that the contract state that reimbursement be made according to Medicare’s medical policies rather than the payer’s.

3. Audits. Commercial payers will claim they have a contractual right to conduct pre- and post-payment audits of physicians’ claims that can result in reduced payments. The contract only states that if doctors correctly submit claims, they will get paid, not that they will have to go through extra steps, which is a breach of their agreement, says Mr. Brodek.

In his experience, 90% of payers back down when asked to provide the contractual basis to conduct these audits. “Or, they take the position that it’s not in the contract but that they have a policy.”

4. Contract amendments versus policies and procedures. This is a huge area that needs to be clarified in contracts and monitored by providers throughout their relationships with payers. Contracts have three elements: the parties, the services provided, and the payment. Changing any one of those terms requires an amendment and advance written notice that has to be delivered to the other party in a certain way, such as by overnight delivery, says Mr. Brodek.

In addition, both parties have to sign that they agree to an amendment. “But, that’s too cumbersome and complicated for payers who have decided to adopt policies instead. These are unilateral changes made with no advance notice given, since the payer typically posts the change on its website,” says Mr. Brodek.

5. Recoupment efforts. Payers will review claims after they’re paid and contact the doctor saying they found a mistake, such as inappropriate coding. They will claim that the doctor now owes them a large sum of money based on a percentage of claims reviewed. “They typically send the doctor a letter that ends with, ‘If you do not pay this amount within 30 days, we will offset the amount due against future payments that we would otherwise make to you,’” says Mr. Brodek.

He recommends that contracts include the doctors’ right to contest an audit so the “payer doesn’t have the unilateral right to disregard the initial coding that the doctor appropriately assigned to the claim and recoup the money anyway,” says Mr. Brodek.

6. Medical network rentals and products. Most contracts say that payers can rent out their medical networks to other health plans, such as HMOs, and that the clinicians agree to comply with all of their policies and procedures. The agreement may also cover the products of other plans.

“The problem is that physicians are not given information about the other plans, including their terms and conditions for getting paid,” says Mr. Brodek. If a problem with payment arises, they have no written agreement with that plan, which makes it harder to enforce.

“That’s why we recommend that doctors negotiate agreements that only cover the main payer. Most of the time, the payer is amenable to putting that language in the contract,” he says.

7. Payer products. In the past several years, a typical contract has included appendices that list the payer’s products, such as Medicare, workers compensation, auto insurance liability, or health care exchange products. Many clinicians don’t realize they can pick the plans they want to participate in by accepting or opting out, says Mr. Brodek.

“We advise clients to limit the contract to what you want covered and to make informed decisions, because some products have low fees set by the states, such as workers compensation and health care exchanges,” says Mr. Brodek.

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

Doctors who are unhappy with low insurance payments may be able to level the playing field and negotiate better rates in their contracts, say experts in physician-payer contracts.

Many doctors sign long-term agreements and then forget about them, says Marcia Brauchler, president and founder of Physicians’ Ally, Littleton, Colorado, a health care consulting company. “The average doctor is trying to run a practice on 2010 rates because they haven’t touched their insurance contracts for 10 years,” she says.

Payers also make a lot of money by adopting dozens of unilateral policy and procedure changes every year that they know physicians are too busy to read. They are counting on the fact that few doctors will understand what the policy changes are and that even fewer will contest them, says Greg Brodek, JD, chair of the health law practice group and head of the managed care litigation practice at Duane Morris, who represents doctors in disputes with payers.

These experts say doctors can push back on one-sided payer contracts and negotiate changes. Mr. Brodek says some practices have more leverage than others to influence payers – if they are larger, in a specialty that the payer needs in its network, or located in a remote area where the payer has limited options.

Here are seven key areas to pay attention to:

1. Long-term contracts. Most doctors sign multiyear “evergreen” contracts that renew automatically every year. This allows insurers to continue to pay doctors the same rate for years.

To avoid this, doctors should negotiate new rates when their agreements renew or, if they prefer, ask that a cost-of-living adjustment be included in the multiyear contract that applies to subsequent years, says Ms. Brauchler.

2. Fee schedules. Payers will “whitewash” what they’re paying you by saying it’s 100% of the payer fee schedule. When it comes to Medicare, they may be paying you a lot less, says Ms. Brauchler.

“My biggest takeaway is to compare the CPT codes of the payer’s fee schedule against what Medicare allows. For example, for CPT code 99213, a 15-minute established office visit, if Medicare pays you $100 and Aetna pays you $75.00, you’re getting 75% of Medicare,” says Ms. Brauchler. To avoid this, doctors should ask that the contract state that reimbursement be made according to Medicare’s medical policies rather than the payer’s.

3. Audits. Commercial payers will claim they have a contractual right to conduct pre- and post-payment audits of physicians’ claims that can result in reduced payments. The contract only states that if doctors correctly submit claims, they will get paid, not that they will have to go through extra steps, which is a breach of their agreement, says Mr. Brodek.

In his experience, 90% of payers back down when asked to provide the contractual basis to conduct these audits. “Or, they take the position that it’s not in the contract but that they have a policy.”

4. Contract amendments versus policies and procedures. This is a huge area that needs to be clarified in contracts and monitored by providers throughout their relationships with payers. Contracts have three elements: the parties, the services provided, and the payment. Changing any one of those terms requires an amendment and advance written notice that has to be delivered to the other party in a certain way, such as by overnight delivery, says Mr. Brodek.

In addition, both parties have to sign that they agree to an amendment. “But, that’s too cumbersome and complicated for payers who have decided to adopt policies instead. These are unilateral changes made with no advance notice given, since the payer typically posts the change on its website,” says Mr. Brodek.

5. Recoupment efforts. Payers will review claims after they’re paid and contact the doctor saying they found a mistake, such as inappropriate coding. They will claim that the doctor now owes them a large sum of money based on a percentage of claims reviewed. “They typically send the doctor a letter that ends with, ‘If you do not pay this amount within 30 days, we will offset the amount due against future payments that we would otherwise make to you,’” says Mr. Brodek.

He recommends that contracts include the doctors’ right to contest an audit so the “payer doesn’t have the unilateral right to disregard the initial coding that the doctor appropriately assigned to the claim and recoup the money anyway,” says Mr. Brodek.

6. Medical network rentals and products. Most contracts say that payers can rent out their medical networks to other health plans, such as HMOs, and that the clinicians agree to comply with all of their policies and procedures. The agreement may also cover the products of other plans.

“The problem is that physicians are not given information about the other plans, including their terms and conditions for getting paid,” says Mr. Brodek. If a problem with payment arises, they have no written agreement with that plan, which makes it harder to enforce.

“That’s why we recommend that doctors negotiate agreements that only cover the main payer. Most of the time, the payer is amenable to putting that language in the contract,” he says.

7. Payer products. In the past several years, a typical contract has included appendices that list the payer’s products, such as Medicare, workers compensation, auto insurance liability, or health care exchange products. Many clinicians don’t realize they can pick the plans they want to participate in by accepting or opting out, says Mr. Brodek.

“We advise clients to limit the contract to what you want covered and to make informed decisions, because some products have low fees set by the states, such as workers compensation and health care exchanges,” says Mr. Brodek.

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

Depending on the data you’re looking at, 40%-60% of physicians are burned out.

Research studies and the eye test reveal the painfully obvious: Colleagues are tired, winded, spent, and at times way past burned out. People aren’t asking me if they’re burned out. They know they’re burned out; heck, they can even recite the Maslach burnout inventory, forward and backward, in a mask, or while completing a COVID quarantine. A fair share of people know the key steps to prevent burnout and promote recovery.

What I’m starting to see more of is, “Why should I even bother to recover from this? Why pick myself up again just to get another occupational stress injury (burnout, demoralization, moral injury, etc.)?” In other words, it’s not just simply about negating burnout; it’s about supporting and facilitating the motivation to work.

We’ve been through so much with COVID that it might be challenging to remember when you saw a truly engaged work environment. No doubt, we have outstanding professionals across medicine who answer the bell every day. However, if you’ve been looking closely, many teams/units have lost a bit of the zip and pep. The synergy and trust aren’t as smooth, and at noon, everyone counts the hours to the end of the shift.

You may be thinking, Well, of course, they are; we’re still amid a pandemic, and people have been through hell. Your observation would be correct, except I’ve personally seen some teams weather the pandemic storm and still remain engaged (some even more involved).

The No. 1 consult result for the GW Resiliency and Well-Being Center, where I work, has been on lectures for burnout. The R&WC has given so many of these lectures that my dreams take the form of a PowerPoint presentation. Overall the talks have gone very well. We’ve added skills sections on practices of whole-person care. We’ve blitzed the daylights out of restorative sleep, yet I know we are still searching for the correct narrative.

Motivated staff, faculty, and students will genuinely take in the information and follow the recommendations; however, they still struggle to find that drive and zest for work. Yes, moving from burnout to neutral is reasonable but likely won’t move the needle of your professional or personal life. We need to have the emotional energy and the clear desire to utilize that energy for a meaningful purpose.

Talking about burnout in specific ways is straightforward and, in my opinion, much easier than talking about engagement. Part of the challenge when trying to discuss engagement is that people can feel invalidated or that you’re telling them to be stoic. Or worse yet, that the problem of burnout primarily lies with them. It’s essential to recognize the role of an organizational factor in burnout (approximately 80%, depending on the study); still, even if you address burnout, people may not be miserable, but it doesn’t mean they will stay at their current job (please cue intro music for the Great Resignation).

Engagement models have existed for some time and certainly have gained much more attention in health care settings over the past 2 decades. Engagement can be described as having three components: dedication, vigor, and absorption. When a person is filling all three of these components over time, presto – you get the much-sought-after state of the supremely engaged professional.

These models definitely give us excellent starting points to approach engagement from a pre-COVID era. In COVID and beyond, I’m not sure how these models will stand up in a hybrid work environment, where autonomy and flexibility could be more valued than ever. Personally, COVID revealed some things I was missing in my work pre-COVID:

• Time to think and process. This was one of the great things about being a consultation-liaison psychiatrist; it was literally feast or famine.
• Doing what I’m talented at and really enjoy.
• Time is short, and I want to be more present in the life of my family.
• Growth and curiosity are vitally important to me. These have to be part of my daily ritual and practice.

The list above isn’t exhaustive, but I’ve found them to be my own personal recipe for being engaged. Over the next series of articles, I’m going to focus on engagement and factors related to key resilience. These articles will be informed by a front-line view from my colleagues, and hopefully start to separate the myth from reality on the subject of health professional engagement and resilience.

Everyone be safe and well!

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

Depending on the data you’re looking at, 40%-60% of physicians are burned out.

Research studies and the eye test reveal the painfully obvious: Colleagues are tired, winded, spent, and at times way past burned out. People aren’t asking me if they’re burned out. They know they’re burned out; heck, they can even recite the Maslach burnout inventory, forward and backward, in a mask, or while completing a COVID quarantine. A fair share of people know the key steps to prevent burnout and promote recovery.

What I’m starting to see more of is, “Why should I even bother to recover from this? Why pick myself up again just to get another occupational stress injury (burnout, demoralization, moral injury, etc.)?” In other words, it’s not just simply about negating burnout; it’s about supporting and facilitating the motivation to work.

We’ve been through so much with COVID that it might be challenging to remember when you saw a truly engaged work environment. No doubt, we have outstanding professionals across medicine who answer the bell every day. However, if you’ve been looking closely, many teams/units have lost a bit of the zip and pep. The synergy and trust aren’t as smooth, and at noon, everyone counts the hours to the end of the shift.

You may be thinking, Well, of course, they are; we’re still amid a pandemic, and people have been through hell. Your observation would be correct, except I’ve personally seen some teams weather the pandemic storm and still remain engaged (some even more involved).

The No. 1 consult result for the GW Resiliency and Well-Being Center, where I work, has been on lectures for burnout. The R&WC has given so many of these lectures that my dreams take the form of a PowerPoint presentation. Overall the talks have gone very well. We’ve added skills sections on practices of whole-person care. We’ve blitzed the daylights out of restorative sleep, yet I know we are still searching for the correct narrative.

Motivated staff, faculty, and students will genuinely take in the information and follow the recommendations; however, they still struggle to find that drive and zest for work. Yes, moving from burnout to neutral is reasonable but likely won’t move the needle of your professional or personal life. We need to have the emotional energy and the clear desire to utilize that energy for a meaningful purpose.

Talking about burnout in specific ways is straightforward and, in my opinion, much easier than talking about engagement. Part of the challenge when trying to discuss engagement is that people can feel invalidated or that you’re telling them to be stoic. Or worse yet, that the problem of burnout primarily lies with them. It’s essential to recognize the role of an organizational factor in burnout (approximately 80%, depending on the study); still, even if you address burnout, people may not be miserable, but it doesn’t mean they will stay at their current job (please cue intro music for the Great Resignation).

Engagement models have existed for some time and certainly have gained much more attention in health care settings over the past 2 decades. Engagement can be described as having three components: dedication, vigor, and absorption. When a person is filling all three of these components over time, presto – you get the much-sought-after state of the supremely engaged professional.

These models definitely give us excellent starting points to approach engagement from a pre-COVID era. In COVID and beyond, I’m not sure how these models will stand up in a hybrid work environment, where autonomy and flexibility could be more valued than ever. Personally, COVID revealed some things I was missing in my work pre-COVID:

• Time to think and process. This was one of the great things about being a consultation-liaison psychiatrist; it was literally feast or famine.
• Doing what I’m talented at and really enjoy.
• Time is short, and I want to be more present in the life of my family.
• Growth and curiosity are vitally important to me. These have to be part of my daily ritual and practice.

The list above isn’t exhaustive, but I’ve found them to be my own personal recipe for being engaged. Over the next series of articles, I’m going to focus on engagement and factors related to key resilience. These articles will be informed by a front-line view from my colleagues, and hopefully start to separate the myth from reality on the subject of health professional engagement and resilience.

Everyone be safe and well!

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

Depending on the data you’re looking at, 40%-60% of physicians are burned out.

Research studies and the eye test reveal the painfully obvious: Colleagues are tired, winded, spent, and at times way past burned out. People aren’t asking me if they’re burned out. They know they’re burned out; heck, they can even recite the Maslach burnout inventory, forward and backward, in a mask, or while completing a COVID quarantine. A fair share of people know the key steps to prevent burnout and promote recovery.

What I’m starting to see more of is, “Why should I even bother to recover from this? Why pick myself up again just to get another occupational stress injury (burnout, demoralization, moral injury, etc.)?” In other words, it’s not just simply about negating burnout; it’s about supporting and facilitating the motivation to work.

We’ve been through so much with COVID that it might be challenging to remember when you saw a truly engaged work environment. No doubt, we have outstanding professionals across medicine who answer the bell every day. However, if you’ve been looking closely, many teams/units have lost a bit of the zip and pep. The synergy and trust aren’t as smooth, and at noon, everyone counts the hours to the end of the shift.

You may be thinking, Well, of course, they are; we’re still amid a pandemic, and people have been through hell. Your observation would be correct, except I’ve personally seen some teams weather the pandemic storm and still remain engaged (some even more involved).

The No. 1 consult result for the GW Resiliency and Well-Being Center, where I work, has been on lectures for burnout. The R&WC has given so many of these lectures that my dreams take the form of a PowerPoint presentation. Overall the talks have gone very well. We’ve added skills sections on practices of whole-person care. We’ve blitzed the daylights out of restorative sleep, yet I know we are still searching for the correct narrative.

Motivated staff, faculty, and students will genuinely take in the information and follow the recommendations; however, they still struggle to find that drive and zest for work. Yes, moving from burnout to neutral is reasonable but likely won’t move the needle of your professional or personal life. We need to have the emotional energy and the clear desire to utilize that energy for a meaningful purpose.

Talking about burnout in specific ways is straightforward and, in my opinion, much easier than talking about engagement. Part of the challenge when trying to discuss engagement is that people can feel invalidated or that you’re telling them to be stoic. Or worse yet, that the problem of burnout primarily lies with them. It’s essential to recognize the role of an organizational factor in burnout (approximately 80%, depending on the study); still, even if you address burnout, people may not be miserable, but it doesn’t mean they will stay at their current job (please cue intro music for the Great Resignation).

Engagement models have existed for some time and certainly have gained much more attention in health care settings over the past 2 decades. Engagement can be described as having three components: dedication, vigor, and absorption. When a person is filling all three of these components over time, presto – you get the much-sought-after state of the supremely engaged professional.

These models definitely give us excellent starting points to approach engagement from a pre-COVID era. In COVID and beyond, I’m not sure how these models will stand up in a hybrid work environment, where autonomy and flexibility could be more valued than ever. Personally, COVID revealed some things I was missing in my work pre-COVID:

• Time to think and process. This was one of the great things about being a consultation-liaison psychiatrist; it was literally feast or famine.
• Doing what I’m talented at and really enjoy.
• Time is short, and I want to be more present in the life of my family.
• Growth and curiosity are vitally important to me. These have to be part of my daily ritual and practice.

The list above isn’t exhaustive, but I’ve found them to be my own personal recipe for being engaged. Over the next series of articles, I’m going to focus on engagement and factors related to key resilience. These articles will be informed by a front-line view from my colleagues, and hopefully start to separate the myth from reality on the subject of health professional engagement and resilience.

Everyone be safe and well!

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

Disruption of the bacteria in the gut is linked with susceptibility to long COVID-19 syndrome, according to new findings.

While links have been found between the gut’s microbiome and COVID-19, as well as other diseases, this is the first published research to show a link specifically to COVID’s long-term effects, the investigators, based at the Chinese University of Hong Kong, wrote in Gut.

Courtesy Dr. Siew Ng

“To our knowledge, this is the first study to show that altered gut microbiome composition is strongly associated with persistent symptoms in patients with COVID-19 up to 6 months after clearance of SARS-CoV-2 virus,” said Siew Ng, MBBS, PhD, associate director at the university’s Center for Gut Microbiota Research.

At three hospitals, the researchers enrolled 106 patients with COVID-19 from February to August 2020 with stool samples at admission and at 1 month and 6 months after discharge, and compared them with people who did not have COVID, recruited in 2019. The severity of COVID in the enrolled patients was mostly mild to moderate.

At 3 months, 86 of the patients with COVID had post–acute COVID-19 syndrome (PACS) – defined as at least one persistent, otherwise unexplained symptom 4 weeks after clearance of the virus. And 81 patients had PACS at 6 months, most commonly fatigue, poor memory, hair loss, anxiety, and trouble sleeping.

Using stool samples for their analysis, the researchers found that, broadly, the diversity of the types of bacteria, and the abundance of these bacteria, were significantly lower at 6 months for those with PACS, compared with those without PACS and with controls (P < .05 and P < .0001, respectively). Among those with PACS, 28 bacteria species were diminished and 14 were enriched, both at baseline and follow-up. Those patients who had COVID but not PACS showed just 25 alterations of bacteria species at the time of hospital admission, and they all normalized by 6 months.

Having respiratory symptoms at 6 months was linked with higher levels of opportunistic pathogens such as Streptococcus anginosus and S. vestibularis. Neuropsychiatric symptoms and fatigue were associated with nosocomial pathogens that are linked to opportunistic infections, such as Clostridium innocuum and Actinomyces naeslundii (P < .05).

Bacteria known for producing butyrate, a beneficial fatty acid, were significantly depleted in those patients with hair loss. And certain of these bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii, had the largest inverse correlations with PACS at 6 months (P < .05), the researchers found.

“Particular gut microbial profiles may indicate heightened susceptibility,” Dr. Ng said.

Although the findings were drawn from patients with earlier strains of the COVID-19 virus, the findings still apply to new variants, including Omicron, since these pose the same problem of persistent disruption of the immune system, Dr. Ng said.

Her group is conducting trials to look at how modulating the microbiome might prevent long COVID and boost antibodies after vaccination in high-risk people, she said.

“Gut microbiota influences the health of the host,” Dr. Ng said. “It provides crucial benefits in the form of immune system development, prevention of infections, nutrient acquisition, and brain and nervous system functionality. Considering the millions of people infected during the ongoing pandemic, our findings are a strong impetus for consideration of microbiota modulation to facilitate timely recovery and reduce the burden of post–acute COVID-19 syndrome.”

Courtesy Dr. John Haran

John Haran, MD, PhD, associate professor of microbiology and physiological systems and emergency medicine at the University of Massachusetts, Worcester, said the research adds to the evidence base on the gut microbiome’s links to COVID, but there was likely be no clinical impact yet. Still, he said the findings linking specific species to specific symptoms was particularly interesting.

“Very early on during hospitalization, [the researchers] saw these differences and correlated out with people who have longer symptoms, and especially different groups of people that have longer symptoms, too,” said Dr. Haran, who has done research on the topic. “It’s very different if you have different symptoms, for example, you keep coughing for months versus you have brain fog and fatigue, or other debilitating symptoms.”

Dr. Haran noted that the findings didn’t identify bacteria types especially linked to COVID, but rather species that have already been found to be associated with a “bad” microbiome. He also pointed out that the patients enrolled in the study were not vaccinated, because vaccines weren’t available at the time. Still, further study to see whether modulation of gut bacteria can be a therapy seems worthwhile.

“Microbiome modulation is pretty safe, and that’s really the next big step that needs to be taken in this,” he said.

For now, the findings don’t give the clinician much new ammunition for treatment.

“We’re not there yet,” he added. “It’s not as if clinicians are going to tell their COVID patients: ‘Go out and buy some kale.’ ”

Eugene Chang, MD, professor of medicine at the University of Chicago, who has studied the gut microbiome and gastrointestinal disease, said it’s “too preliminary” to say whether the findings could lead to a clinical impact. The measures used merely identify the microbes present, but not what they are doing.

“These measures are unlikely to perform well enough to be useful for risk assessment or predicting clinical outcomes,” he said. “That being said, advances in technology are being made where next generations of metrics could be developed and useful as stratifiers and predictors of risk.”

Seeing shifting patterns associated with certain symptoms, he said, is “notable because it suggests that the disturbances of the gut microbiota in PACS are significant.”

But he said it’s important to know whether these changes are a cause of PACS in some way or just an effect of it.

“If causative or contributory – this has to be proven – then ‘microbiota modulation’ would make sense and could be a priority for development,” he said. “If merely an effect, these metrics and better ones to come could be useful as predictors or measures of the patient’s general state of health.”

As seen in his group’s work and other work, he said, “the gut microbiota is highly sensitive to changes in their ecosystem, which is influenced by the health state of the patient.”

Dr. Ng, Dr. Haran, and Dr. Chang reported no relevant disclosures.

This article was updated Jan. 27, 2022.

Disruption of the bacteria in the gut is linked with susceptibility to long COVID-19 syndrome, according to new findings.

While links have been found between the gut’s microbiome and COVID-19, as well as other diseases, this is the first published research to show a link specifically to COVID’s long-term effects, the investigators, based at the Chinese University of Hong Kong, wrote in Gut.

Courtesy Dr. Siew Ng

“To our knowledge, this is the first study to show that altered gut microbiome composition is strongly associated with persistent symptoms in patients with COVID-19 up to 6 months after clearance of SARS-CoV-2 virus,” said Siew Ng, MBBS, PhD, associate director at the university’s Center for Gut Microbiota Research.

At three hospitals, the researchers enrolled 106 patients with COVID-19 from February to August 2020 with stool samples at admission and at 1 month and 6 months after discharge, and compared them with people who did not have COVID, recruited in 2019. The severity of COVID in the enrolled patients was mostly mild to moderate.

At 3 months, 86 of the patients with COVID had post–acute COVID-19 syndrome (PACS) – defined as at least one persistent, otherwise unexplained symptom 4 weeks after clearance of the virus. And 81 patients had PACS at 6 months, most commonly fatigue, poor memory, hair loss, anxiety, and trouble sleeping.

Using stool samples for their analysis, the researchers found that, broadly, the diversity of the types of bacteria, and the abundance of these bacteria, were significantly lower at 6 months for those with PACS, compared with those without PACS and with controls (P < .05 and P < .0001, respectively). Among those with PACS, 28 bacteria species were diminished and 14 were enriched, both at baseline and follow-up. Those patients who had COVID but not PACS showed just 25 alterations of bacteria species at the time of hospital admission, and they all normalized by 6 months.

Having respiratory symptoms at 6 months was linked with higher levels of opportunistic pathogens such as Streptococcus anginosus and S. vestibularis. Neuropsychiatric symptoms and fatigue were associated with nosocomial pathogens that are linked to opportunistic infections, such as Clostridium innocuum and Actinomyces naeslundii (P < .05).

Bacteria known for producing butyrate, a beneficial fatty acid, were significantly depleted in those patients with hair loss. And certain of these bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii, had the largest inverse correlations with PACS at 6 months (P < .05), the researchers found.

“Particular gut microbial profiles may indicate heightened susceptibility,” Dr. Ng said.

Although the findings were drawn from patients with earlier strains of the COVID-19 virus, the findings still apply to new variants, including Omicron, since these pose the same problem of persistent disruption of the immune system, Dr. Ng said.

Her group is conducting trials to look at how modulating the microbiome might prevent long COVID and boost antibodies after vaccination in high-risk people, she said.

“Gut microbiota influences the health of the host,” Dr. Ng said. “It provides crucial benefits in the form of immune system development, prevention of infections, nutrient acquisition, and brain and nervous system functionality. Considering the millions of people infected during the ongoing pandemic, our findings are a strong impetus for consideration of microbiota modulation to facilitate timely recovery and reduce the burden of post–acute COVID-19 syndrome.”

Courtesy Dr. John Haran

John Haran, MD, PhD, associate professor of microbiology and physiological systems and emergency medicine at the University of Massachusetts, Worcester, said the research adds to the evidence base on the gut microbiome’s links to COVID, but there was likely be no clinical impact yet. Still, he said the findings linking specific species to specific symptoms was particularly interesting.

“Very early on during hospitalization, [the researchers] saw these differences and correlated out with people who have longer symptoms, and especially different groups of people that have longer symptoms, too,” said Dr. Haran, who has done research on the topic. “It’s very different if you have different symptoms, for example, you keep coughing for months versus you have brain fog and fatigue, or other debilitating symptoms.”

Dr. Haran noted that the findings didn’t identify bacteria types especially linked to COVID, but rather species that have already been found to be associated with a “bad” microbiome. He also pointed out that the patients enrolled in the study were not vaccinated, because vaccines weren’t available at the time. Still, further study to see whether modulation of gut bacteria can be a therapy seems worthwhile.

“Microbiome modulation is pretty safe, and that’s really the next big step that needs to be taken in this,” he said.

For now, the findings don’t give the clinician much new ammunition for treatment.

“We’re not there yet,” he added. “It’s not as if clinicians are going to tell their COVID patients: ‘Go out and buy some kale.’ ”

Eugene Chang, MD, professor of medicine at the University of Chicago, who has studied the gut microbiome and gastrointestinal disease, said it’s “too preliminary” to say whether the findings could lead to a clinical impact. The measures used merely identify the microbes present, but not what they are doing.

“These measures are unlikely to perform well enough to be useful for risk assessment or predicting clinical outcomes,” he said. “That being said, advances in technology are being made where next generations of metrics could be developed and useful as stratifiers and predictors of risk.”

Seeing shifting patterns associated with certain symptoms, he said, is “notable because it suggests that the disturbances of the gut microbiota in PACS are significant.”

But he said it’s important to know whether these changes are a cause of PACS in some way or just an effect of it.

“If causative or contributory – this has to be proven – then ‘microbiota modulation’ would make sense and could be a priority for development,” he said. “If merely an effect, these metrics and better ones to come could be useful as predictors or measures of the patient’s general state of health.”

As seen in his group’s work and other work, he said, “the gut microbiota is highly sensitive to changes in their ecosystem, which is influenced by the health state of the patient.”

Dr. Ng, Dr. Haran, and Dr. Chang reported no relevant disclosures.

This article was updated Jan. 27, 2022.

Disruption of the bacteria in the gut is linked with susceptibility to long COVID-19 syndrome, according to new findings.

While links have been found between the gut’s microbiome and COVID-19, as well as other diseases, this is the first published research to show a link specifically to COVID’s long-term effects, the investigators, based at the Chinese University of Hong Kong, wrote in Gut.

Courtesy Dr. Siew Ng

“To our knowledge, this is the first study to show that altered gut microbiome composition is strongly associated with persistent symptoms in patients with COVID-19 up to 6 months after clearance of SARS-CoV-2 virus,” said Siew Ng, MBBS, PhD, associate director at the university’s Center for Gut Microbiota Research.

At three hospitals, the researchers enrolled 106 patients with COVID-19 from February to August 2020 with stool samples at admission and at 1 month and 6 months after discharge, and compared them with people who did not have COVID, recruited in 2019. The severity of COVID in the enrolled patients was mostly mild to moderate.

At 3 months, 86 of the patients with COVID had post–acute COVID-19 syndrome (PACS) – defined as at least one persistent, otherwise unexplained symptom 4 weeks after clearance of the virus. And 81 patients had PACS at 6 months, most commonly fatigue, poor memory, hair loss, anxiety, and trouble sleeping.

Using stool samples for their analysis, the researchers found that, broadly, the diversity of the types of bacteria, and the abundance of these bacteria, were significantly lower at 6 months for those with PACS, compared with those without PACS and with controls (P < .05 and P < .0001, respectively). Among those with PACS, 28 bacteria species were diminished and 14 were enriched, both at baseline and follow-up. Those patients who had COVID but not PACS showed just 25 alterations of bacteria species at the time of hospital admission, and they all normalized by 6 months.

Having respiratory symptoms at 6 months was linked with higher levels of opportunistic pathogens such as Streptococcus anginosus and S. vestibularis. Neuropsychiatric symptoms and fatigue were associated with nosocomial pathogens that are linked to opportunistic infections, such as Clostridium innocuum and Actinomyces naeslundii (P < .05).

Bacteria known for producing butyrate, a beneficial fatty acid, were significantly depleted in those patients with hair loss. And certain of these bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii, had the largest inverse correlations with PACS at 6 months (P < .05), the researchers found.

“Particular gut microbial profiles may indicate heightened susceptibility,” Dr. Ng said.

Although the findings were drawn from patients with earlier strains of the COVID-19 virus, the findings still apply to new variants, including Omicron, since these pose the same problem of persistent disruption of the immune system, Dr. Ng said.

Her group is conducting trials to look at how modulating the microbiome might prevent long COVID and boost antibodies after vaccination in high-risk people, she said.

“Gut microbiota influences the health of the host,” Dr. Ng said. “It provides crucial benefits in the form of immune system development, prevention of infections, nutrient acquisition, and brain and nervous system functionality. Considering the millions of people infected during the ongoing pandemic, our findings are a strong impetus for consideration of microbiota modulation to facilitate timely recovery and reduce the burden of post–acute COVID-19 syndrome.”

Courtesy Dr. John Haran

John Haran, MD, PhD, associate professor of microbiology and physiological systems and emergency medicine at the University of Massachusetts, Worcester, said the research adds to the evidence base on the gut microbiome’s links to COVID, but there was likely be no clinical impact yet. Still, he said the findings linking specific species to specific symptoms was particularly interesting.

“Very early on during hospitalization, [the researchers] saw these differences and correlated out with people who have longer symptoms, and especially different groups of people that have longer symptoms, too,” said Dr. Haran, who has done research on the topic. “It’s very different if you have different symptoms, for example, you keep coughing for months versus you have brain fog and fatigue, or other debilitating symptoms.”

Dr. Haran noted that the findings didn’t identify bacteria types especially linked to COVID, but rather species that have already been found to be associated with a “bad” microbiome. He also pointed out that the patients enrolled in the study were not vaccinated, because vaccines weren’t available at the time. Still, further study to see whether modulation of gut bacteria can be a therapy seems worthwhile.

“Microbiome modulation is pretty safe, and that’s really the next big step that needs to be taken in this,” he said.

For now, the findings don’t give the clinician much new ammunition for treatment.

“We’re not there yet,” he added. “It’s not as if clinicians are going to tell their COVID patients: ‘Go out and buy some kale.’ ”

Eugene Chang, MD, professor of medicine at the University of Chicago, who has studied the gut microbiome and gastrointestinal disease, said it’s “too preliminary” to say whether the findings could lead to a clinical impact. The measures used merely identify the microbes present, but not what they are doing.

“These measures are unlikely to perform well enough to be useful for risk assessment or predicting clinical outcomes,” he said. “That being said, advances in technology are being made where next generations of metrics could be developed and useful as stratifiers and predictors of risk.”

Seeing shifting patterns associated with certain symptoms, he said, is “notable because it suggests that the disturbances of the gut microbiota in PACS are significant.”

But he said it’s important to know whether these changes are a cause of PACS in some way or just an effect of it.

“If causative or contributory – this has to be proven – then ‘microbiota modulation’ would make sense and could be a priority for development,” he said. “If merely an effect, these metrics and better ones to come could be useful as predictors or measures of the patient’s general state of health.”

As seen in his group’s work and other work, he said, “the gut microbiota is highly sensitive to changes in their ecosystem, which is influenced by the health state of the patient.”

Dr. Ng, Dr. Haran, and Dr. Chang reported no relevant disclosures.

This article was updated Jan. 27, 2022.

Can you tell which of the following statements are true and which are false?

COVID-19 is not a threat to younger people, and only those who have other medical conditions are dying from it.

The mRNA vaccines developed to prevent the coronavirus alter your genes, can make your body “magnetic,” and are killing more people than the virus itself.

President Joe Biden’s climate change plan calls for a ban on meat consumption to cut greenhouse gas emissions.

The 2020 presidential election was rigged and stolen.

If you guessed that all of these claims are false, you’re right – take a bow. Not a single one of these statements has any factual support, according to scientific research, legal rulings, and legitimate government authorities.

And yet public opinion surveys show millions of Americans, and others around the world, believe some of these falsehoods are true and can’t be convinced otherwise.

Social media, politicians and partisan websites, TV programs, and commentators have widely circulated these and other unfounded claims so frequently that many people say they simply can’t tell what’s objectively true and not anymore.

So much so, the authors of a fascinating new research study have concluded we are living in a “post-truth era,” with baseless beliefs and subjective opinions given a higher priority than verifiable facts.

The new study – The Rise and Fall of Rationality in Language, published in the Proceedings of the National Academy of Sciences – found that facts have become less important in public discourse.

As a result, unsupported beliefs have taken precedent over readily identifiable truths in discussions of health, science, and politics. The upshot: “Feelings trump facts” in social media, news reports, books, and other sources of information.

And here’s the kicker: The trend did not begin with the rise of former President Donald Trump, the COVID-19 pandemic, or the advent of social media; in fact, it has been growing for much longer than you might think.

“While the current ‘post-truth era’ has taken many by surprise, the study shows that over the past 40 years, public interest has undergone an accelerating shift from the collective to the individual, and from rationality towards emotion,” concluded the researchers from Indiana University and Wageningen University & Research in the Netherlands.

“Our work suggests that the societal balance between emotion and reason has shifted back to what it used to be around 150 years ago,” says lead researcher Marten Scheffer, PhD, a professor in the department of environmental sciences at WUR. “This implies that scientists, experts, and policymakers will have to think about the best way to respond to that social change.”
 

Researchers surprised by findings

The findings are based on a very detailed analysis of language from millions of books, newspaper articles, Google searches, TV reports, social media posts, and other sources dating back to 1850.

The researchers analyzed how often the 5,000 most used words appeared over the past 170 years and found that the use of those having to do with facts and reasoning, such as “determine” and “conclusion,” has fallen dramatically since 1980. Meanwhile, the use of words related to human emotion, such as “feel” and “believe,” have skyrocketed.

Dr. Scheffer notes rapid developments in science and technology from 1850 to 1980 had profound social and economic benefits that helped boost the status of the scientific approach. That shift in public attitudes had ripple effects on culture, society, education, politics, and religion – and “the role of spiritualism dwindled” in the modern world, he says.

But since 1980, that trend has seen a major reversal, with beliefs becoming more important than facts to many people, he says. At the same time, trust in science and scientists has fallen.

Dr. Scheffer says the researchers expected to find some evidence of a swing toward more belief-based sentiments during the Trump era but were surprised to discover how strong it is and that the trend has actually been a long time coming.

“The shift in interest from rational to intuitive/emotional is pretty obvious now in the post-truth political and social media discussion,” he says. “However, our work shows that it already started in the 1980s. For me personally, that went under the radar, except perhaps for the rise of alternative (to religion) forms of spirituality.

“We were especially struck by how strong the patterns are and how universal they appear across languages, nonfiction and fiction, and even in The New York Times.”

In the political world, the implications are significant enough – impacting policies and politicians on both sides of the aisle and across the globe. Just look at the deepening political divisions during the Trump presidency.

But for health and science, the spread of misinformation and falsehoods can be matters of life or death, as we have seen in the politically charged debates over how best to combat COVID-19 and global climate change.

“Our public debate seems increasingly driven by what people want to be true rather than what is actually true. As a scientist, that worries me,” says study co-author Johan Bollen, PhD, a professor of informatics at Indiana University.

“As a society, we are now faced with major collective problems that we need to approach from a pragmatic, rational, and objective perspective to be successful,” he says. “After all, global warming doesn’t care about whether you believe in it or not … but we will all suffer as a society if we fail to take adequate measures.”

For WUR co-researcher Ingrid van de Leemput, the trend isn’t merely academic; she’s seen it play out in her personal life.

“I do speak to people that, for instance, think the vaccines are poison,” she says. “I’m also on Twitter, and there, I’m every day surprised about how easily many people form their opinions, based on feelings, on what others say, or on some unfounded source.”

Public health experts say the embrace of personal beliefs over facts is one reason only 63% of Americans have been vaccinated against COVID-19. The result: millions of preventable infections among those who downplay the risks of the virus and reject the strong scientific evidence of vaccine safety and effectiveness.

“None of this really surprises me,” Johns Hopkins University social and behavioral scientist Rupali Limaye, PhD, says of the new study findings. Dr. Limaye coauthored a paper in 2016 in JAMA Pediatrics about how to talk to parents about vaccine hesitancy and the fact that we’re living in what they called “this post-truth era.”

Dr. Limaye says the trend has made it difficult for doctors, scientists, and health authorities to make fact-based arguments for COVID-19 vaccination, mask-wearing, social distancing, and other measures to control the virus.

“It’s been really hard being a scientist to hear people say, ‘Well, that’s not true’ when we say something very basic that I think all of us can agree on – like the grass is green,” she says. “To be honest, I worry that a lot of scientists are going to quit being in science because they’re exhausted.”
 

What’s driving the trend?

So, what’s behind the embrace of “alternative facts,” as former White House counselor Kellyanne Conway put it so brazenly in 2017, in defending the White House’s false claims that Trump’s inauguration crowd was the largest ever?

Dr. Scheffer and colleagues identified a handful of things that have encouraged the embrace of falsehoods over facts in recent years.

• The Internet: Its rise in the late 1980s, and its growing role as a primary source of news and information, has allowed more belief-based misinformation to flourish and spread like wildfire.
• Social media: The new study found the use of sentiment- and intuition-related words accelerated around 2007, along with a global surge in social media that catapulted Facebook, Twitter, and others into the mainstream, replacing more traditional fact-based media (i.e., newspapers and magazines).
• The 2007 financial crisis: The downturn in the global economy meant more people were dealing with job stress, investment losses, and other problems that fed the interest in belief-based, anti-establishment social media posts.
• Conspiracy theories: Falsehoods involving hidden political agendas, shadow “elites,” and wealthy people with dark motives tend to thrive during times of crisis and societal anxiety. “Conspiracy theories originate particularly in times of uncertainty and crisis and generally depict established institutions as hiding the truth and sustaining an unfair situation,” the researchers noted. “As a result, they may find fertile grounds on social media platforms promulgating a sense of unfairness, subsequently feeding anti-system sentiments.”

Dr. Scheffer says that growing political divisions during the Trump era have widened the fact-vs.-fiction divide. The ex-president voiced many anti-science views on global climate change, for instance, and spread so many falsehoods about COVID-19 and the 2020 election that Facebook, Twitter, and YouTube suspended his accounts.

Yet Trump remains a popular figure among Republicans, with most saying in a December poll they believe his baseless claims that the 2020 election was “rigged” and “stolen,” despite all credible, easily accessible evidence that it was secure, according to a recent poll by the University of Massachusetts at Amherst.

More than 60 courts have rejected Trump’s lawsuits seeking to overturn the election results. All 50 states, the District of Columbia, and both branches of Congress have certified the election results, giving Biden the White House. Even Trump’s own Justice Department confirmed that the 2020 election was free and fair.

Nevertheless, the University of Massachusetts survey found that most Republicans believe one or more conspiracy theories floated by the former president and those pushing his “big lie” that Democrats rigged the election to elect Biden.

Ed Berliner, an Emmy Award-winning broadcast journalist and media consultant, suggests something else is driving the spread of misinformation: the pursuit of ratings by cable TV and media companies to boost ad and subscriber revenues.

As a former executive producer and syndicated cable TV show host, he says he has seen firsthand how facts are often lost in opinion-driven news programs, even on network programs claiming to offer “fair and balanced” journalism.

“Propaganda is the new currency in America, and those who do not fight back against it are doomed to be overrun by the misinformation,” says Mr. Berliner, host of The Man in the Arena and CEO of Entourage Media LLC.

“The broadcast news media has to stop this incessant ‘infotainment’ prattle, stop trying to nuzzle up to a soft side, and bear down on hard facts, exposing the lies and refusing to back down.”
 

Public health implications

Public health and media experts alike say the PNAS study findings are disheartening but underscore the need for doctors and scientists to do a better job of communicating about COVID-19 and other pressing issues.

Dr. Limaye, from Johns Hopkins, is particularly concerned about the rise in conspiracy theories that has led to COVID-19 vaccine hesitancy.

“When we speak to individuals about getting the COVID vaccine…the types of concerns that come up now are very different than they were 8 years ago,” she says. “The comments we used to hear were much more related to vaccine safety. [People] would say, ‘I’m worried about an ingredient in the vaccine’ or ‘I’m worried that my kiddo has to get three different shots within 6 months to have a series dose completed.’”

But now, a lot of comments they receive are about government and pharma conspiracies.

What that means is doctors and scientists must do more than simply say “here are the facts” and “trust me, I’m a doctor or a scientist,” she says. And these approaches don’t only apply to public health.

“It’s funny, because when we talk to climate change scientists, as vaccine [specialists], we’ll say we can’t believe that people think COVID is a hoax,” she says. “And they’re like, ‘Hold my beer, we’ve been dealing with this for 20 years. Hello, it’s just your guys’ turn to deal with this public denial of science.’”

Dr. Limaye is also concerned about the impacts on funding for scientific research.

“There’s always been a really strong bipartisan effort with regards to funding for science, when you look at Congress and when you look at appropriations,” she says. “But what ended up happening, especially with the Trump administration, was that there was a real shift in that. We’ve never really seen that before in past generations.”

So, what’s the big take-home message?

Dr. Limaye believes doctors and public health experts must show more empathy – and not be combative or arrogant – in communicating science in one-on-one conversations. This month, she’s launching a new course for parents, school administrators, and nurses on how to do precisely that.

“It’s really all about how to have hard conversations with people who might be anti-science,” she says. “It’s being empathetic and not being dismissive. But it’s hard work, and I think a lot of people are just not cut out for it and just don’t have the time for it…You can’t just say, ‘Well, this is science, and I’m a doctor’ – that doesn’t work anymore.”

Brendan Nyhan, PhD, a Dartmouth College political scientist, echoes those sentiments in a separate paper recently published in the Proceedings of the National Academy of Sciences. In fact, he suggests that providing accurate, fact-based information to counter false claims may actually backfire and reinforce some people’s unfounded beliefs.

“One response to the prevalence of mistaken beliefs is to try to set the record straight by providing accurate information – for instance, by providing evidence of the scientific consensus on climate change,” he writes. “The failures of this approach, which is sometimes referred to as the ‘deficit model’ in science communication, are well-known.”

Dr. Nyhan argues two things make some people more prone to believe falsehoods:

What scientists call “ingrouping,” a kind of tribal mentality that makes some people choose social identity or politics over truth-seeking and demonize others who don’t agree with their views

The rise of high-profile political figures, such as Trump, who encourage their followers to indulge in their desire for “identify-affirming misinformation”

Dr. Scheffer says the most important thing for doctors, health experts, and scientists to recognize is that it’s crucial to gain the trust of someone who may believe fictions over facts to make any persuasive argument on COVID-19 or any other issue.

He also has a standard response to those who present falsehoods to him as facts that he suggests anyone can use: “That is interesting. Would you mind helping me understand how you came to that opinion?”

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

Can you tell which of the following statements are true and which are false?

COVID-19 is not a threat to younger people, and only those who have other medical conditions are dying from it.

The mRNA vaccines developed to prevent the coronavirus alter your genes, can make your body “magnetic,” and are killing more people than the virus itself.

President Joe Biden’s climate change plan calls for a ban on meat consumption to cut greenhouse gas emissions.

The 2020 presidential election was rigged and stolen.

If you guessed that all of these claims are false, you’re right – take a bow. Not a single one of these statements has any factual support, according to scientific research, legal rulings, and legitimate government authorities.

And yet public opinion surveys show millions of Americans, and others around the world, believe some of these falsehoods are true and can’t be convinced otherwise.

Social media, politicians and partisan websites, TV programs, and commentators have widely circulated these and other unfounded claims so frequently that many people say they simply can’t tell what’s objectively true and not anymore.

So much so, the authors of a fascinating new research study have concluded we are living in a “post-truth era,” with baseless beliefs and subjective opinions given a higher priority than verifiable facts.

The new study – The Rise and Fall of Rationality in Language, published in the Proceedings of the National Academy of Sciences – found that facts have become less important in public discourse.

As a result, unsupported beliefs have taken precedent over readily identifiable truths in discussions of health, science, and politics. The upshot: “Feelings trump facts” in social media, news reports, books, and other sources of information.

And here’s the kicker: The trend did not begin with the rise of former President Donald Trump, the COVID-19 pandemic, or the advent of social media; in fact, it has been growing for much longer than you might think.

“While the current ‘post-truth era’ has taken many by surprise, the study shows that over the past 40 years, public interest has undergone an accelerating shift from the collective to the individual, and from rationality towards emotion,” concluded the researchers from Indiana University and Wageningen University & Research in the Netherlands.

“Our work suggests that the societal balance between emotion and reason has shifted back to what it used to be around 150 years ago,” says lead researcher Marten Scheffer, PhD, a professor in the department of environmental sciences at WUR. “This implies that scientists, experts, and policymakers will have to think about the best way to respond to that social change.”
 

Researchers surprised by findings

The findings are based on a very detailed analysis of language from millions of books, newspaper articles, Google searches, TV reports, social media posts, and other sources dating back to 1850.

The researchers analyzed how often the 5,000 most used words appeared over the past 170 years and found that the use of those having to do with facts and reasoning, such as “determine” and “conclusion,” has fallen dramatically since 1980. Meanwhile, the use of words related to human emotion, such as “feel” and “believe,” have skyrocketed.

Dr. Scheffer notes rapid developments in science and technology from 1850 to 1980 had profound social and economic benefits that helped boost the status of the scientific approach. That shift in public attitudes had ripple effects on culture, society, education, politics, and religion – and “the role of spiritualism dwindled” in the modern world, he says.

But since 1980, that trend has seen a major reversal, with beliefs becoming more important than facts to many people, he says. At the same time, trust in science and scientists has fallen.

Dr. Scheffer says the researchers expected to find some evidence of a swing toward more belief-based sentiments during the Trump era but were surprised to discover how strong it is and that the trend has actually been a long time coming.

“The shift in interest from rational to intuitive/emotional is pretty obvious now in the post-truth political and social media discussion,” he says. “However, our work shows that it already started in the 1980s. For me personally, that went under the radar, except perhaps for the rise of alternative (to religion) forms of spirituality.

“We were especially struck by how strong the patterns are and how universal they appear across languages, nonfiction and fiction, and even in The New York Times.”

In the political world, the implications are significant enough – impacting policies and politicians on both sides of the aisle and across the globe. Just look at the deepening political divisions during the Trump presidency.

But for health and science, the spread of misinformation and falsehoods can be matters of life or death, as we have seen in the politically charged debates over how best to combat COVID-19 and global climate change.

“Our public debate seems increasingly driven by what people want to be true rather than what is actually true. As a scientist, that worries me,” says study co-author Johan Bollen, PhD, a professor of informatics at Indiana University.

“As a society, we are now faced with major collective problems that we need to approach from a pragmatic, rational, and objective perspective to be successful,” he says. “After all, global warming doesn’t care about whether you believe in it or not … but we will all suffer as a society if we fail to take adequate measures.”

For WUR co-researcher Ingrid van de Leemput, the trend isn’t merely academic; she’s seen it play out in her personal life.

“I do speak to people that, for instance, think the vaccines are poison,” she says. “I’m also on Twitter, and there, I’m every day surprised about how easily many people form their opinions, based on feelings, on what others say, or on some unfounded source.”

Public health experts say the embrace of personal beliefs over facts is one reason only 63% of Americans have been vaccinated against COVID-19. The result: millions of preventable infections among those who downplay the risks of the virus and reject the strong scientific evidence of vaccine safety and effectiveness.

“None of this really surprises me,” Johns Hopkins University social and behavioral scientist Rupali Limaye, PhD, says of the new study findings. Dr. Limaye coauthored a paper in 2016 in JAMA Pediatrics about how to talk to parents about vaccine hesitancy and the fact that we’re living in what they called “this post-truth era.”

Dr. Limaye says the trend has made it difficult for doctors, scientists, and health authorities to make fact-based arguments for COVID-19 vaccination, mask-wearing, social distancing, and other measures to control the virus.

“It’s been really hard being a scientist to hear people say, ‘Well, that’s not true’ when we say something very basic that I think all of us can agree on – like the grass is green,” she says. “To be honest, I worry that a lot of scientists are going to quit being in science because they’re exhausted.”
 

What’s driving the trend?

So, what’s behind the embrace of “alternative facts,” as former White House counselor Kellyanne Conway put it so brazenly in 2017, in defending the White House’s false claims that Trump’s inauguration crowd was the largest ever?

Dr. Scheffer and colleagues identified a handful of things that have encouraged the embrace of falsehoods over facts in recent years.

• The Internet: Its rise in the late 1980s, and its growing role as a primary source of news and information, has allowed more belief-based misinformation to flourish and spread like wildfire.
• Social media: The new study found the use of sentiment- and intuition-related words accelerated around 2007, along with a global surge in social media that catapulted Facebook, Twitter, and others into the mainstream, replacing more traditional fact-based media (i.e., newspapers and magazines).
• The 2007 financial crisis: The downturn in the global economy meant more people were dealing with job stress, investment losses, and other problems that fed the interest in belief-based, anti-establishment social media posts.
• Conspiracy theories: Falsehoods involving hidden political agendas, shadow “elites,” and wealthy people with dark motives tend to thrive during times of crisis and societal anxiety. “Conspiracy theories originate particularly in times of uncertainty and crisis and generally depict established institutions as hiding the truth and sustaining an unfair situation,” the researchers noted. “As a result, they may find fertile grounds on social media platforms promulgating a sense of unfairness, subsequently feeding anti-system sentiments.”

Dr. Scheffer says that growing political divisions during the Trump era have widened the fact-vs.-fiction divide. The ex-president voiced many anti-science views on global climate change, for instance, and spread so many falsehoods about COVID-19 and the 2020 election that Facebook, Twitter, and YouTube suspended his accounts.

Yet Trump remains a popular figure among Republicans, with most saying in a December poll they believe his baseless claims that the 2020 election was “rigged” and “stolen,” despite all credible, easily accessible evidence that it was secure, according to a recent poll by the University of Massachusetts at Amherst.

More than 60 courts have rejected Trump’s lawsuits seeking to overturn the election results. All 50 states, the District of Columbia, and both branches of Congress have certified the election results, giving Biden the White House. Even Trump’s own Justice Department confirmed that the 2020 election was free and fair.

Nevertheless, the University of Massachusetts survey found that most Republicans believe one or more conspiracy theories floated by the former president and those pushing his “big lie” that Democrats rigged the election to elect Biden.

Ed Berliner, an Emmy Award-winning broadcast journalist and media consultant, suggests something else is driving the spread of misinformation: the pursuit of ratings by cable TV and media companies to boost ad and subscriber revenues.

As a former executive producer and syndicated cable TV show host, he says he has seen firsthand how facts are often lost in opinion-driven news programs, even on network programs claiming to offer “fair and balanced” journalism.

“Propaganda is the new currency in America, and those who do not fight back against it are doomed to be overrun by the misinformation,” says Mr. Berliner, host of The Man in the Arena and CEO of Entourage Media LLC.

“The broadcast news media has to stop this incessant ‘infotainment’ prattle, stop trying to nuzzle up to a soft side, and bear down on hard facts, exposing the lies and refusing to back down.”
 

Public health implications

Public health and media experts alike say the PNAS study findings are disheartening but underscore the need for doctors and scientists to do a better job of communicating about COVID-19 and other pressing issues.

Dr. Limaye, from Johns Hopkins, is particularly concerned about the rise in conspiracy theories that has led to COVID-19 vaccine hesitancy.

“When we speak to individuals about getting the COVID vaccine…the types of concerns that come up now are very different than they were 8 years ago,” she says. “The comments we used to hear were much more related to vaccine safety. [People] would say, ‘I’m worried about an ingredient in the vaccine’ or ‘I’m worried that my kiddo has to get three different shots within 6 months to have a series dose completed.’”

But now, a lot of comments they receive are about government and pharma conspiracies.

What that means is doctors and scientists must do more than simply say “here are the facts” and “trust me, I’m a doctor or a scientist,” she says. And these approaches don’t only apply to public health.

“It’s funny, because when we talk to climate change scientists, as vaccine [specialists], we’ll say we can’t believe that people think COVID is a hoax,” she says. “And they’re like, ‘Hold my beer, we’ve been dealing with this for 20 years. Hello, it’s just your guys’ turn to deal with this public denial of science.’”

Dr. Limaye is also concerned about the impacts on funding for scientific research.

“There’s always been a really strong bipartisan effort with regards to funding for science, when you look at Congress and when you look at appropriations,” she says. “But what ended up happening, especially with the Trump administration, was that there was a real shift in that. We’ve never really seen that before in past generations.”

So, what’s the big take-home message?

Dr. Limaye believes doctors and public health experts must show more empathy – and not be combative or arrogant – in communicating science in one-on-one conversations. This month, she’s launching a new course for parents, school administrators, and nurses on how to do precisely that.

“It’s really all about how to have hard conversations with people who might be anti-science,” she says. “It’s being empathetic and not being dismissive. But it’s hard work, and I think a lot of people are just not cut out for it and just don’t have the time for it…You can’t just say, ‘Well, this is science, and I’m a doctor’ – that doesn’t work anymore.”

Brendan Nyhan, PhD, a Dartmouth College political scientist, echoes those sentiments in a separate paper recently published in the Proceedings of the National Academy of Sciences. In fact, he suggests that providing accurate, fact-based information to counter false claims may actually backfire and reinforce some people’s unfounded beliefs.

“One response to the prevalence of mistaken beliefs is to try to set the record straight by providing accurate information – for instance, by providing evidence of the scientific consensus on climate change,” he writes. “The failures of this approach, which is sometimes referred to as the ‘deficit model’ in science communication, are well-known.”

Dr. Nyhan argues two things make some people more prone to believe falsehoods:

What scientists call “ingrouping,” a kind of tribal mentality that makes some people choose social identity or politics over truth-seeking and demonize others who don’t agree with their views

The rise of high-profile political figures, such as Trump, who encourage their followers to indulge in their desire for “identify-affirming misinformation”

Dr. Scheffer says the most important thing for doctors, health experts, and scientists to recognize is that it’s crucial to gain the trust of someone who may believe fictions over facts to make any persuasive argument on COVID-19 or any other issue.

He also has a standard response to those who present falsehoods to him as facts that he suggests anyone can use: “That is interesting. Would you mind helping me understand how you came to that opinion?”

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

Can you tell which of the following statements are true and which are false?

COVID-19 is not a threat to younger people, and only those who have other medical conditions are dying from it.

The mRNA vaccines developed to prevent the coronavirus alter your genes, can make your body “magnetic,” and are killing more people than the virus itself.

President Joe Biden’s climate change plan calls for a ban on meat consumption to cut greenhouse gas emissions.

The 2020 presidential election was rigged and stolen.

If you guessed that all of these claims are false, you’re right – take a bow. Not a single one of these statements has any factual support, according to scientific research, legal rulings, and legitimate government authorities.

And yet public opinion surveys show millions of Americans, and others around the world, believe some of these falsehoods are true and can’t be convinced otherwise.

Social media, politicians and partisan websites, TV programs, and commentators have widely circulated these and other unfounded claims so frequently that many people say they simply can’t tell what’s objectively true and not anymore.

So much so, the authors of a fascinating new research study have concluded we are living in a “post-truth era,” with baseless beliefs and subjective opinions given a higher priority than verifiable facts.

The new study – The Rise and Fall of Rationality in Language, published in the Proceedings of the National Academy of Sciences – found that facts have become less important in public discourse.

As a result, unsupported beliefs have taken precedent over readily identifiable truths in discussions of health, science, and politics. The upshot: “Feelings trump facts” in social media, news reports, books, and other sources of information.

And here’s the kicker: The trend did not begin with the rise of former President Donald Trump, the COVID-19 pandemic, or the advent of social media; in fact, it has been growing for much longer than you might think.

“While the current ‘post-truth era’ has taken many by surprise, the study shows that over the past 40 years, public interest has undergone an accelerating shift from the collective to the individual, and from rationality towards emotion,” concluded the researchers from Indiana University and Wageningen University & Research in the Netherlands.

“Our work suggests that the societal balance between emotion and reason has shifted back to what it used to be around 150 years ago,” says lead researcher Marten Scheffer, PhD, a professor in the department of environmental sciences at WUR. “This implies that scientists, experts, and policymakers will have to think about the best way to respond to that social change.”
 

Researchers surprised by findings

The findings are based on a very detailed analysis of language from millions of books, newspaper articles, Google searches, TV reports, social media posts, and other sources dating back to 1850.

The researchers analyzed how often the 5,000 most used words appeared over the past 170 years and found that the use of those having to do with facts and reasoning, such as “determine” and “conclusion,” has fallen dramatically since 1980. Meanwhile, the use of words related to human emotion, such as “feel” and “believe,” have skyrocketed.

Dr. Scheffer notes rapid developments in science and technology from 1850 to 1980 had profound social and economic benefits that helped boost the status of the scientific approach. That shift in public attitudes had ripple effects on culture, society, education, politics, and religion – and “the role of spiritualism dwindled” in the modern world, he says.

But since 1980, that trend has seen a major reversal, with beliefs becoming more important than facts to many people, he says. At the same time, trust in science and scientists has fallen.

Dr. Scheffer says the researchers expected to find some evidence of a swing toward more belief-based sentiments during the Trump era but were surprised to discover how strong it is and that the trend has actually been a long time coming.

“The shift in interest from rational to intuitive/emotional is pretty obvious now in the post-truth political and social media discussion,” he says. “However, our work shows that it already started in the 1980s. For me personally, that went under the radar, except perhaps for the rise of alternative (to religion) forms of spirituality.

“We were especially struck by how strong the patterns are and how universal they appear across languages, nonfiction and fiction, and even in The New York Times.”

In the political world, the implications are significant enough – impacting policies and politicians on both sides of the aisle and across the globe. Just look at the deepening political divisions during the Trump presidency.

But for health and science, the spread of misinformation and falsehoods can be matters of life or death, as we have seen in the politically charged debates over how best to combat COVID-19 and global climate change.

“Our public debate seems increasingly driven by what people want to be true rather than what is actually true. As a scientist, that worries me,” says study co-author Johan Bollen, PhD, a professor of informatics at Indiana University.

“As a society, we are now faced with major collective problems that we need to approach from a pragmatic, rational, and objective perspective to be successful,” he says. “After all, global warming doesn’t care about whether you believe in it or not … but we will all suffer as a society if we fail to take adequate measures.”

For WUR co-researcher Ingrid van de Leemput, the trend isn’t merely academic; she’s seen it play out in her personal life.

“I do speak to people that, for instance, think the vaccines are poison,” she says. “I’m also on Twitter, and there, I’m every day surprised about how easily many people form their opinions, based on feelings, on what others say, or on some unfounded source.”

Public health experts say the embrace of personal beliefs over facts is one reason only 63% of Americans have been vaccinated against COVID-19. The result: millions of preventable infections among those who downplay the risks of the virus and reject the strong scientific evidence of vaccine safety and effectiveness.

“None of this really surprises me,” Johns Hopkins University social and behavioral scientist Rupali Limaye, PhD, says of the new study findings. Dr. Limaye coauthored a paper in 2016 in JAMA Pediatrics about how to talk to parents about vaccine hesitancy and the fact that we’re living in what they called “this post-truth era.”

Dr. Limaye says the trend has made it difficult for doctors, scientists, and health authorities to make fact-based arguments for COVID-19 vaccination, mask-wearing, social distancing, and other measures to control the virus.

“It’s been really hard being a scientist to hear people say, ‘Well, that’s not true’ when we say something very basic that I think all of us can agree on – like the grass is green,” she says. “To be honest, I worry that a lot of scientists are going to quit being in science because they’re exhausted.”
 

What’s driving the trend?

So, what’s behind the embrace of “alternative facts,” as former White House counselor Kellyanne Conway put it so brazenly in 2017, in defending the White House’s false claims that Trump’s inauguration crowd was the largest ever?

Dr. Scheffer and colleagues identified a handful of things that have encouraged the embrace of falsehoods over facts in recent years.

• The Internet: Its rise in the late 1980s, and its growing role as a primary source of news and information, has allowed more belief-based misinformation to flourish and spread like wildfire.
• Social media: The new study found the use of sentiment- and intuition-related words accelerated around 2007, along with a global surge in social media that catapulted Facebook, Twitter, and others into the mainstream, replacing more traditional fact-based media (i.e., newspapers and magazines).
• The 2007 financial crisis: The downturn in the global economy meant more people were dealing with job stress, investment losses, and other problems that fed the interest in belief-based, anti-establishment social media posts.
• Conspiracy theories: Falsehoods involving hidden political agendas, shadow “elites,” and wealthy people with dark motives tend to thrive during times of crisis and societal anxiety. “Conspiracy theories originate particularly in times of uncertainty and crisis and generally depict established institutions as hiding the truth and sustaining an unfair situation,” the researchers noted. “As a result, they may find fertile grounds on social media platforms promulgating a sense of unfairness, subsequently feeding anti-system sentiments.”

Dr. Scheffer says that growing political divisions during the Trump era have widened the fact-vs.-fiction divide. The ex-president voiced many anti-science views on global climate change, for instance, and spread so many falsehoods about COVID-19 and the 2020 election that Facebook, Twitter, and YouTube suspended his accounts.

Yet Trump remains a popular figure among Republicans, with most saying in a December poll they believe his baseless claims that the 2020 election was “rigged” and “stolen,” despite all credible, easily accessible evidence that it was secure, according to a recent poll by the University of Massachusetts at Amherst.

More than 60 courts have rejected Trump’s lawsuits seeking to overturn the election results. All 50 states, the District of Columbia, and both branches of Congress have certified the election results, giving Biden the White House. Even Trump’s own Justice Department confirmed that the 2020 election was free and fair.

Nevertheless, the University of Massachusetts survey found that most Republicans believe one or more conspiracy theories floated by the former president and those pushing his “big lie” that Democrats rigged the election to elect Biden.

Ed Berliner, an Emmy Award-winning broadcast journalist and media consultant, suggests something else is driving the spread of misinformation: the pursuit of ratings by cable TV and media companies to boost ad and subscriber revenues.

As a former executive producer and syndicated cable TV show host, he says he has seen firsthand how facts are often lost in opinion-driven news programs, even on network programs claiming to offer “fair and balanced” journalism.

“Propaganda is the new currency in America, and those who do not fight back against it are doomed to be overrun by the misinformation,” says Mr. Berliner, host of The Man in the Arena and CEO of Entourage Media LLC.

“The broadcast news media has to stop this incessant ‘infotainment’ prattle, stop trying to nuzzle up to a soft side, and bear down on hard facts, exposing the lies and refusing to back down.”
 

Public health implications

Public health and media experts alike say the PNAS study findings are disheartening but underscore the need for doctors and scientists to do a better job of communicating about COVID-19 and other pressing issues.

Dr. Limaye, from Johns Hopkins, is particularly concerned about the rise in conspiracy theories that has led to COVID-19 vaccine hesitancy.

“When we speak to individuals about getting the COVID vaccine…the types of concerns that come up now are very different than they were 8 years ago,” she says. “The comments we used to hear were much more related to vaccine safety. [People] would say, ‘I’m worried about an ingredient in the vaccine’ or ‘I’m worried that my kiddo has to get three different shots within 6 months to have a series dose completed.’”

But now, a lot of comments they receive are about government and pharma conspiracies.

What that means is doctors and scientists must do more than simply say “here are the facts” and “trust me, I’m a doctor or a scientist,” she says. And these approaches don’t only apply to public health.

“It’s funny, because when we talk to climate change scientists, as vaccine [specialists], we’ll say we can’t believe that people think COVID is a hoax,” she says. “And they’re like, ‘Hold my beer, we’ve been dealing with this for 20 years. Hello, it’s just your guys’ turn to deal with this public denial of science.’”

Dr. Limaye is also concerned about the impacts on funding for scientific research.

“There’s always been a really strong bipartisan effort with regards to funding for science, when you look at Congress and when you look at appropriations,” she says. “But what ended up happening, especially with the Trump administration, was that there was a real shift in that. We’ve never really seen that before in past generations.”

So, what’s the big take-home message?

Dr. Limaye believes doctors and public health experts must show more empathy – and not be combative or arrogant – in communicating science in one-on-one conversations. This month, she’s launching a new course for parents, school administrators, and nurses on how to do precisely that.

“It’s really all about how to have hard conversations with people who might be anti-science,” she says. “It’s being empathetic and not being dismissive. But it’s hard work, and I think a lot of people are just not cut out for it and just don’t have the time for it…You can’t just say, ‘Well, this is science, and I’m a doctor’ – that doesn’t work anymore.”

Brendan Nyhan, PhD, a Dartmouth College political scientist, echoes those sentiments in a separate paper recently published in the Proceedings of the National Academy of Sciences. In fact, he suggests that providing accurate, fact-based information to counter false claims may actually backfire and reinforce some people’s unfounded beliefs.

“One response to the prevalence of mistaken beliefs is to try to set the record straight by providing accurate information – for instance, by providing evidence of the scientific consensus on climate change,” he writes. “The failures of this approach, which is sometimes referred to as the ‘deficit model’ in science communication, are well-known.”

Dr. Nyhan argues two things make some people more prone to believe falsehoods:

What scientists call “ingrouping,” a kind of tribal mentality that makes some people choose social identity or politics over truth-seeking and demonize others who don’t agree with their views

The rise of high-profile political figures, such as Trump, who encourage their followers to indulge in their desire for “identify-affirming misinformation”

Dr. Scheffer says the most important thing for doctors, health experts, and scientists to recognize is that it’s crucial to gain the trust of someone who may believe fictions over facts to make any persuasive argument on COVID-19 or any other issue.

He also has a standard response to those who present falsehoods to him as facts that he suggests anyone can use: “That is interesting. Would you mind helping me understand how you came to that opinion?”

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

In another salvo in the heated debate over treatment for kids who believe they’re transgender, a study published in PLoS One suggests that transgender adults who received hormone therapy as teenagers are mentally healthier in a pair of ways than those who didn’t.

The study, which only looks at transgender adults, doesn’t confirm that hormone therapy in childhood is a beneficial treatment. Still, “we found that for all age groups, access to [adolescent] gender-affirming hormone initiation was associated with lower odds of past-year suicidal ideation and past-month severe psychological distress measured in adulthood,” said lead author Jack Turban, MD, chief fellow in child and adolescent psychiatry at Stanford (Calif.) University, in an interview. “We also found better mental-health outcomes for those who started gender-affirming hormones as adolescents when compared to those who didn’t start them until they were adults.”

The use of hormone treatment and puberty blockers by transgender teens is extremely controversial. Critics say the treatments are harmful and unnecessary, and Republican politicians are trying to ban their use in some states. Last spring, Arkansas became the first state to ban the treatments. The law is on hold amid a legal challenge.

The researchers launched the study to gain more insight into the impact of hormone therapy on children. “There have been several longitudinal studies showing that mental health improves following gender-affirming medical care for transgender youth, but there has been less research looking at the relationship between when these medications are started and adult mental health outcomes,” Dr. Turban said. “This is the first study to look at various ages of initiation of gender-affirming hormones and compare outcomes between those who started gender-affirming hormones during adolescence and those who did not start them until adulthood.”

For the new study, the authors analyzed the findings of the 2015 U.S. Transgender Survey of 27,715 adults and focused on 21,598 who said they’d wanted hormone therapy (40% aged 18-24, 83% White, 35% transgender male, 41% transgender female, with the rest using other terms such as “queer” or “nonbinary” to describe themselves).

Of these subjects, 41.0% never received hormone therapy, 0.6% underwent therapy in early adolescence, 1.7% received it in late adolescence, and 56.8% got it as adults.

The researchers made various adjustments for confounders – age, partnership status, employment status, K-12 harassment, and experience of gender identity conversion efforts. Those who received hormone therapy had lower odds of past-year suicidal ideation vs. those who didn’t: adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.6; P < .0001 for therapy that occurred from age 14 to 15, aOR, 0.5; 95% CI, 0.4-0.7; P < .0001, for therapy that occurred from age 16 to 17, and aOR, 0.8; 95% CI, 0.7-0.8; P < .0001 for therapy that occurred in adulthood.

However, there was no statistically significant link between hormone therapy and past-year suicidal ideation with a plan or past-year suicide attempt.

The study also found lower rates of past-month severe psychological distress: aOR. 0.3; 95% CI, 0.2-0.4; P < .0001 for therapy from age 14 to 15, aOR, 0.3; 95% CI, 0.3-0.4; P < .0001 for therapy from age 16 to 17, and aOR, 0.6 (95% CI, 0.5-0.6; P < .0001) for therapy in adulthood.

There was no statistically significant link between hormone therapy and past-month binge drinking or lifetime illicit drug use.

“The findings indicate that clinicians caring for adolescents need to be properly trained in gender-affirming medical care, including hormone therapy, in order to help promote good mental health outcomes for transgender people. Comprehensive training in gender-affirming care is currently not part of standard medical education curricula,” said study coauthor Alex Keuroghlian, MD, MPH, director of the National LGBTQIA+ Health Education Center at the Fenway Institute and associate professor of psychiatry at Harvard Medical School, Boston, in an interview.

The study has limitations. The survey population doesn’t include anyone who committed suicide, nor does it include people who had gender dysphoria as children but didn’t go on to identify as transgender as adults. It is also retrospective. “There is a general consensus that, given the data we have so far, it would be unethical to conduct a randomized controlled trial in this space,” said study lead author Dr. Turban.

Several critics of hormone therapy in teens support a psychotherapy-based approach to gender dysphoria that considers whether other factors are at play than transgender orientation. They’ve united to attack research based on the 2015 transgender survey. In a 2021 report in Archives of Sexual Behavior, they called it “a highly skewed sample” and objected to “a conflation of ethical nonaffirmative psychotherapy with conversion therapy.”

In an interview, one of the critics – developmental psychologist and retired University of Sydney professor Dianna Kenny, PhD – said the new study’s “serious problem of recall bias” about hormone therapy in the survey is “insurmountable.” The survey, she said, also fails to explore why participants who wanted hormone therapy didn’t get it.

Dr. Kenny, who believes all hormone therapy in teens with gender dysphoria outside of clinical trials is inappropriate, also pointed out that hormone therapy has many side effects. She added that young people with gender dysphoria often “realize through a process of cognitive and psychosocial maturation that they were not ‘genuinely’ trans but suffering from other conditions that needed treatment – e.g., internalized homophobia, trauma, including sexual abuse, attention-deficit/hyperactivity disorder, autism spectrum disorder, etc.”

No specific funding is reported, although two of the authors report receiving various grants, fellowship and research funding. Dr. Turban discloses textbook royalties from Springer Nature and expert witness payments from the ACLU. Dr. Keuroghlian discloses textbook royalties from McGraw Hill. Dr. Kenny reports no disclosures.

In another salvo in the heated debate over treatment for kids who believe they’re transgender, a study published in PLoS One suggests that transgender adults who received hormone therapy as teenagers are mentally healthier in a pair of ways than those who didn’t.

The study, which only looks at transgender adults, doesn’t confirm that hormone therapy in childhood is a beneficial treatment. Still, “we found that for all age groups, access to [adolescent] gender-affirming hormone initiation was associated with lower odds of past-year suicidal ideation and past-month severe psychological distress measured in adulthood,” said lead author Jack Turban, MD, chief fellow in child and adolescent psychiatry at Stanford (Calif.) University, in an interview. “We also found better mental-health outcomes for those who started gender-affirming hormones as adolescents when compared to those who didn’t start them until they were adults.”

The use of hormone treatment and puberty blockers by transgender teens is extremely controversial. Critics say the treatments are harmful and unnecessary, and Republican politicians are trying to ban their use in some states. Last spring, Arkansas became the first state to ban the treatments. The law is on hold amid a legal challenge.

The researchers launched the study to gain more insight into the impact of hormone therapy on children. “There have been several longitudinal studies showing that mental health improves following gender-affirming medical care for transgender youth, but there has been less research looking at the relationship between when these medications are started and adult mental health outcomes,” Dr. Turban said. “This is the first study to look at various ages of initiation of gender-affirming hormones and compare outcomes between those who started gender-affirming hormones during adolescence and those who did not start them until adulthood.”

For the new study, the authors analyzed the findings of the 2015 U.S. Transgender Survey of 27,715 adults and focused on 21,598 who said they’d wanted hormone therapy (40% aged 18-24, 83% White, 35% transgender male, 41% transgender female, with the rest using other terms such as “queer” or “nonbinary” to describe themselves).

Of these subjects, 41.0% never received hormone therapy, 0.6% underwent therapy in early adolescence, 1.7% received it in late adolescence, and 56.8% got it as adults.

The researchers made various adjustments for confounders – age, partnership status, employment status, K-12 harassment, and experience of gender identity conversion efforts. Those who received hormone therapy had lower odds of past-year suicidal ideation vs. those who didn’t: adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.6; P < .0001 for therapy that occurred from age 14 to 15, aOR, 0.5; 95% CI, 0.4-0.7; P < .0001, for therapy that occurred from age 16 to 17, and aOR, 0.8; 95% CI, 0.7-0.8; P < .0001 for therapy that occurred in adulthood.

However, there was no statistically significant link between hormone therapy and past-year suicidal ideation with a plan or past-year suicide attempt.

The study also found lower rates of past-month severe psychological distress: aOR. 0.3; 95% CI, 0.2-0.4; P < .0001 for therapy from age 14 to 15, aOR, 0.3; 95% CI, 0.3-0.4; P < .0001 for therapy from age 16 to 17, and aOR, 0.6 (95% CI, 0.5-0.6; P < .0001) for therapy in adulthood.

There was no statistically significant link between hormone therapy and past-month binge drinking or lifetime illicit drug use.

“The findings indicate that clinicians caring for adolescents need to be properly trained in gender-affirming medical care, including hormone therapy, in order to help promote good mental health outcomes for transgender people. Comprehensive training in gender-affirming care is currently not part of standard medical education curricula,” said study coauthor Alex Keuroghlian, MD, MPH, director of the National LGBTQIA+ Health Education Center at the Fenway Institute and associate professor of psychiatry at Harvard Medical School, Boston, in an interview.

The study has limitations. The survey population doesn’t include anyone who committed suicide, nor does it include people who had gender dysphoria as children but didn’t go on to identify as transgender as adults. It is also retrospective. “There is a general consensus that, given the data we have so far, it would be unethical to conduct a randomized controlled trial in this space,” said study lead author Dr. Turban.

Several critics of hormone therapy in teens support a psychotherapy-based approach to gender dysphoria that considers whether other factors are at play than transgender orientation. They’ve united to attack research based on the 2015 transgender survey. In a 2021 report in Archives of Sexual Behavior, they called it “a highly skewed sample” and objected to “a conflation of ethical nonaffirmative psychotherapy with conversion therapy.”

In an interview, one of the critics – developmental psychologist and retired University of Sydney professor Dianna Kenny, PhD – said the new study’s “serious problem of recall bias” about hormone therapy in the survey is “insurmountable.” The survey, she said, also fails to explore why participants who wanted hormone therapy didn’t get it.

Dr. Kenny, who believes all hormone therapy in teens with gender dysphoria outside of clinical trials is inappropriate, also pointed out that hormone therapy has many side effects. She added that young people with gender dysphoria often “realize through a process of cognitive and psychosocial maturation that they were not ‘genuinely’ trans but suffering from other conditions that needed treatment – e.g., internalized homophobia, trauma, including sexual abuse, attention-deficit/hyperactivity disorder, autism spectrum disorder, etc.”

No specific funding is reported, although two of the authors report receiving various grants, fellowship and research funding. Dr. Turban discloses textbook royalties from Springer Nature and expert witness payments from the ACLU. Dr. Keuroghlian discloses textbook royalties from McGraw Hill. Dr. Kenny reports no disclosures.

In another salvo in the heated debate over treatment for kids who believe they’re transgender, a study published in PLoS One suggests that transgender adults who received hormone therapy as teenagers are mentally healthier in a pair of ways than those who didn’t.

The study, which only looks at transgender adults, doesn’t confirm that hormone therapy in childhood is a beneficial treatment. Still, “we found that for all age groups, access to [adolescent] gender-affirming hormone initiation was associated with lower odds of past-year suicidal ideation and past-month severe psychological distress measured in adulthood,” said lead author Jack Turban, MD, chief fellow in child and adolescent psychiatry at Stanford (Calif.) University, in an interview. “We also found better mental-health outcomes for those who started gender-affirming hormones as adolescents when compared to those who didn’t start them until they were adults.”

The use of hormone treatment and puberty blockers by transgender teens is extremely controversial. Critics say the treatments are harmful and unnecessary, and Republican politicians are trying to ban their use in some states. Last spring, Arkansas became the first state to ban the treatments. The law is on hold amid a legal challenge.

The researchers launched the study to gain more insight into the impact of hormone therapy on children. “There have been several longitudinal studies showing that mental health improves following gender-affirming medical care for transgender youth, but there has been less research looking at the relationship between when these medications are started and adult mental health outcomes,” Dr. Turban said. “This is the first study to look at various ages of initiation of gender-affirming hormones and compare outcomes between those who started gender-affirming hormones during adolescence and those who did not start them until adulthood.”

For the new study, the authors analyzed the findings of the 2015 U.S. Transgender Survey of 27,715 adults and focused on 21,598 who said they’d wanted hormone therapy (40% aged 18-24, 83% White, 35% transgender male, 41% transgender female, with the rest using other terms such as “queer” or “nonbinary” to describe themselves).

Of these subjects, 41.0% never received hormone therapy, 0.6% underwent therapy in early adolescence, 1.7% received it in late adolescence, and 56.8% got it as adults.

The researchers made various adjustments for confounders – age, partnership status, employment status, K-12 harassment, and experience of gender identity conversion efforts. Those who received hormone therapy had lower odds of past-year suicidal ideation vs. those who didn’t: adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.6; P < .0001 for therapy that occurred from age 14 to 15, aOR, 0.5; 95% CI, 0.4-0.7; P < .0001, for therapy that occurred from age 16 to 17, and aOR, 0.8; 95% CI, 0.7-0.8; P < .0001 for therapy that occurred in adulthood.

However, there was no statistically significant link between hormone therapy and past-year suicidal ideation with a plan or past-year suicide attempt.

The study also found lower rates of past-month severe psychological distress: aOR. 0.3; 95% CI, 0.2-0.4; P < .0001 for therapy from age 14 to 15, aOR, 0.3; 95% CI, 0.3-0.4; P < .0001 for therapy from age 16 to 17, and aOR, 0.6 (95% CI, 0.5-0.6; P < .0001) for therapy in adulthood.

There was no statistically significant link between hormone therapy and past-month binge drinking or lifetime illicit drug use.

“The findings indicate that clinicians caring for adolescents need to be properly trained in gender-affirming medical care, including hormone therapy, in order to help promote good mental health outcomes for transgender people. Comprehensive training in gender-affirming care is currently not part of standard medical education curricula,” said study coauthor Alex Keuroghlian, MD, MPH, director of the National LGBTQIA+ Health Education Center at the Fenway Institute and associate professor of psychiatry at Harvard Medical School, Boston, in an interview.

The study has limitations. The survey population doesn’t include anyone who committed suicide, nor does it include people who had gender dysphoria as children but didn’t go on to identify as transgender as adults. It is also retrospective. “There is a general consensus that, given the data we have so far, it would be unethical to conduct a randomized controlled trial in this space,” said study lead author Dr. Turban.

Several critics of hormone therapy in teens support a psychotherapy-based approach to gender dysphoria that considers whether other factors are at play than transgender orientation. They’ve united to attack research based on the 2015 transgender survey. In a 2021 report in Archives of Sexual Behavior, they called it “a highly skewed sample” and objected to “a conflation of ethical nonaffirmative psychotherapy with conversion therapy.”

In an interview, one of the critics – developmental psychologist and retired University of Sydney professor Dianna Kenny, PhD – said the new study’s “serious problem of recall bias” about hormone therapy in the survey is “insurmountable.” The survey, she said, also fails to explore why participants who wanted hormone therapy didn’t get it.

Dr. Kenny, who believes all hormone therapy in teens with gender dysphoria outside of clinical trials is inappropriate, also pointed out that hormone therapy has many side effects. She added that young people with gender dysphoria often “realize through a process of cognitive and psychosocial maturation that they were not ‘genuinely’ trans but suffering from other conditions that needed treatment – e.g., internalized homophobia, trauma, including sexual abuse, attention-deficit/hyperactivity disorder, autism spectrum disorder, etc.”

No specific funding is reported, although two of the authors report receiving various grants, fellowship and research funding. Dr. Turban discloses textbook royalties from Springer Nature and expert witness payments from the ACLU. Dr. Keuroghlian discloses textbook royalties from McGraw Hill. Dr. Kenny reports no disclosures.

Patients with breast cancer treated with chemotherapy who also took a probiotics supplement had significantly fewer symptoms of chemotherapy-related cognitive impairment (CRCI) often referred to as “chemo brain,” compared with a control group taking placebo capsules, reports the first study of its kind.

“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.

The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.

The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.

The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).

The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.

He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”

“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.

Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.

“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.

“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.

A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
 

Measuring the effect on ‘chemo brain’

“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.

In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.

The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).

Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).

The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).

The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.

CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.

In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.

There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
 

How does it work?

The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.

A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.

Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
 

Benefits reported beyond breast cancer

A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.

And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.

The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.

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

Patients with breast cancer treated with chemotherapy who also took a probiotics supplement had significantly fewer symptoms of chemotherapy-related cognitive impairment (CRCI) often referred to as “chemo brain,” compared with a control group taking placebo capsules, reports the first study of its kind.

“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.

The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.

The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.

The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).

The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.

He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”

“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.

Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.

“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.

“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.

A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
 

Measuring the effect on ‘chemo brain’

“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.

In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.

The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).

Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).

The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).

The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.

CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.

In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.

There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
 

How does it work?

The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.

A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.

Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
 

Benefits reported beyond breast cancer

A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.

And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.

The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.

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

Patients with breast cancer treated with chemotherapy who also took a probiotics supplement had significantly fewer symptoms of chemotherapy-related cognitive impairment (CRCI) often referred to as “chemo brain,” compared with a control group taking placebo capsules, reports the first study of its kind.

“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.

The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.

The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.

The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).

The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.

He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”

“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.

Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.

“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.

“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.

A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
 

Measuring the effect on ‘chemo brain’

“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.

In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.

The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).

Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).

The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).

The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.

CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.

In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.

There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
 

How does it work?

The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.

A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.

Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
 

Benefits reported beyond breast cancer

A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.

And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.

The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.

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