In August I shared with you my observations on two opposing op-ed pieces from two major newspapers, one was in favor of masking mandates for public schools, the other against. (Masking in school: A battle of the op-eds. MDedge Pediatrics. Letters from Maine, 2021 Aug 12). Neither group of authors could offer us evidence from controlled studies to support their views. However, both agreed that returning children to school deserves a high priority. But neither the authors nor I treaded into the uncharted waters of exactly how masking fits into our national goals for managing the pandemic because ... no one in this country has articulated what these goals should be. A third op-ed appearing 3 weeks later suggests why we are floundering in this goal-deficient limbo.

Writing in the New York Times, two epidemiologists in Boston ask the simple question: “What are we actually trying to achieve in the United States?” when it comes to the pandemic. (Allen AG and Jenkins H. The Hard Covid-19 Questions We’re Not Asking. 2021 Aug 30). Is our goal zero infections? Is it hammering on the virus until we can treat it like the seasonal flu? We do seem to agree that not having kids in school has been a disaster economically, educationally, and psychologically. But, where does the goal of getting them back in school fit into a larger and as yet undefined national goal? Without that target we have little idea of what compromises and risks we should be willing to accept.

How much serious pediatric disease is acceptable? It appears that the number of fatal complications in the pediatric population is very small in comparison with other demographic groups. Although few in number, there have been and there will continue to be pediatric deaths because of COVID. Is our goal zero pediatric deaths? If it is then this dictates a level of response that ripples back upstream to every child in every classroom and could threaten our overarching goal of returning children to school. Because none of us likes the thought of a child dying, some of us may be hesitant to even consider a strategy that doesn’t include zero pediatric deaths as a goal.

Are we looking to have zero serious pediatric infections? Achieving this goal is unlikely. Even if we develop a pediatric vaccine in the near future it probably won’t be in the arms of enough children by the end of this school year to make a significant dent in the number of serious pediatric infections. Waiting until an optimal number of children are immunized doesn’t feel like it will achieve a primary goal of getting kids back in school if we continue to focus on driving the level of serious pediatric infections to zero. We have already endured a year in which many communities made decisions that seemed to have prioritized an unstated goal of no school exposure–related educator deaths. Again, a goal based on little if any evidence.

The problem we face in this country is that our response to the pandemic has been nonuniform. Here in Brunswick, Maine, 99% of the eligible adults have been vaccinated. Even with the recent surge, we may be ready for a strategy that avoids wholesale quarantining. A targeted and robust antibody testing system might work for us and make an unproven and unpopular masking mandate unnecessary. Britain seems to be moving in a similar direction to meet its goal of keeping children in school.

However, there are large population groups in regions of this country that have stumbled at taking the initial steps to get the pandemic under control. Articulating a national goal that covers both communities where the response to the pandemic has been less thoughtful and robust along with states that have been more successful is going to be difficult. But it must be done.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

In August I shared with you my observations on two opposing op-ed pieces from two major newspapers, one was in favor of masking mandates for public schools, the other against. (Masking in school: A battle of the op-eds. MDedge Pediatrics. Letters from Maine, 2021 Aug 12). Neither group of authors could offer us evidence from controlled studies to support their views. However, both agreed that returning children to school deserves a high priority. But neither the authors nor I treaded into the uncharted waters of exactly how masking fits into our national goals for managing the pandemic because ... no one in this country has articulated what these goals should be. A third op-ed appearing 3 weeks later suggests why we are floundering in this goal-deficient limbo.

Writing in the New York Times, two epidemiologists in Boston ask the simple question: “What are we actually trying to achieve in the United States?” when it comes to the pandemic. (Allen AG and Jenkins H. The Hard Covid-19 Questions We’re Not Asking. 2021 Aug 30). Is our goal zero infections? Is it hammering on the virus until we can treat it like the seasonal flu? We do seem to agree that not having kids in school has been a disaster economically, educationally, and psychologically. But, where does the goal of getting them back in school fit into a larger and as yet undefined national goal? Without that target we have little idea of what compromises and risks we should be willing to accept.

How much serious pediatric disease is acceptable? It appears that the number of fatal complications in the pediatric population is very small in comparison with other demographic groups. Although few in number, there have been and there will continue to be pediatric deaths because of COVID. Is our goal zero pediatric deaths? If it is then this dictates a level of response that ripples back upstream to every child in every classroom and could threaten our overarching goal of returning children to school. Because none of us likes the thought of a child dying, some of us may be hesitant to even consider a strategy that doesn’t include zero pediatric deaths as a goal.

Are we looking to have zero serious pediatric infections? Achieving this goal is unlikely. Even if we develop a pediatric vaccine in the near future it probably won’t be in the arms of enough children by the end of this school year to make a significant dent in the number of serious pediatric infections. Waiting until an optimal number of children are immunized doesn’t feel like it will achieve a primary goal of getting kids back in school if we continue to focus on driving the level of serious pediatric infections to zero. We have already endured a year in which many communities made decisions that seemed to have prioritized an unstated goal of no school exposure–related educator deaths. Again, a goal based on little if any evidence.

The problem we face in this country is that our response to the pandemic has been nonuniform. Here in Brunswick, Maine, 99% of the eligible adults have been vaccinated. Even with the recent surge, we may be ready for a strategy that avoids wholesale quarantining. A targeted and robust antibody testing system might work for us and make an unproven and unpopular masking mandate unnecessary. Britain seems to be moving in a similar direction to meet its goal of keeping children in school.

However, there are large population groups in regions of this country that have stumbled at taking the initial steps to get the pandemic under control. Articulating a national goal that covers both communities where the response to the pandemic has been less thoughtful and robust along with states that have been more successful is going to be difficult. But it must be done.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

In August I shared with you my observations on two opposing op-ed pieces from two major newspapers, one was in favor of masking mandates for public schools, the other against. (Masking in school: A battle of the op-eds. MDedge Pediatrics. Letters from Maine, 2021 Aug 12). Neither group of authors could offer us evidence from controlled studies to support their views. However, both agreed that returning children to school deserves a high priority. But neither the authors nor I treaded into the uncharted waters of exactly how masking fits into our national goals for managing the pandemic because ... no one in this country has articulated what these goals should be. A third op-ed appearing 3 weeks later suggests why we are floundering in this goal-deficient limbo.

Writing in the New York Times, two epidemiologists in Boston ask the simple question: “What are we actually trying to achieve in the United States?” when it comes to the pandemic. (Allen AG and Jenkins H. The Hard Covid-19 Questions We’re Not Asking. 2021 Aug 30). Is our goal zero infections? Is it hammering on the virus until we can treat it like the seasonal flu? We do seem to agree that not having kids in school has been a disaster economically, educationally, and psychologically. But, where does the goal of getting them back in school fit into a larger and as yet undefined national goal? Without that target we have little idea of what compromises and risks we should be willing to accept.

How much serious pediatric disease is acceptable? It appears that the number of fatal complications in the pediatric population is very small in comparison with other demographic groups. Although few in number, there have been and there will continue to be pediatric deaths because of COVID. Is our goal zero pediatric deaths? If it is then this dictates a level of response that ripples back upstream to every child in every classroom and could threaten our overarching goal of returning children to school. Because none of us likes the thought of a child dying, some of us may be hesitant to even consider a strategy that doesn’t include zero pediatric deaths as a goal.

Are we looking to have zero serious pediatric infections? Achieving this goal is unlikely. Even if we develop a pediatric vaccine in the near future it probably won’t be in the arms of enough children by the end of this school year to make a significant dent in the number of serious pediatric infections. Waiting until an optimal number of children are immunized doesn’t feel like it will achieve a primary goal of getting kids back in school if we continue to focus on driving the level of serious pediatric infections to zero. We have already endured a year in which many communities made decisions that seemed to have prioritized an unstated goal of no school exposure–related educator deaths. Again, a goal based on little if any evidence.

The problem we face in this country is that our response to the pandemic has been nonuniform. Here in Brunswick, Maine, 99% of the eligible adults have been vaccinated. Even with the recent surge, we may be ready for a strategy that avoids wholesale quarantining. A targeted and robust antibody testing system might work for us and make an unproven and unpopular masking mandate unnecessary. Britain seems to be moving in a similar direction to meet its goal of keeping children in school.

However, there are large population groups in regions of this country that have stumbled at taking the initial steps to get the pandemic under control. Articulating a national goal that covers both communities where the response to the pandemic has been less thoughtful and robust along with states that have been more successful is going to be difficult. But it must be done.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

As private practices try to recover and rebuild in the wake of the COVID-19 pandemic, many have faced an unexpected challenge: a paucity of employees.

My own office is prime example: I have had job listings for both front- and back-office positions posted on all the major job boards and other employment portals for months, with a disappointing response. Of the few who do respond, many, incredibly, do not show up for their interviews!

It turns out that this is a widespread problem, and not just in medicine. A recent survey by the National Federation of Independent Business found that 42% of business owners, in all walks of life, had job openings that could not be filled, a record high. Over 90% of those hiring reported few or no qualified applicants and an increase in interview no-shows.

Clearly, this is a huge obstacle to growth – and even to conducting normal operations – for my practice and many others.

Reasons for the situation vary, but a big one has been the unfortunate fact that many open job positions actually pay less than the expanded unemployment benefits that many people have received under the March 2020 CARES Act. By one estimate, almost 70% of unemployed workers have been collecting more on unemployment than they earned while working. The CARES benefits expired in early September, but many potential workers continue to receive payments through a newer FEMA program, and some states have their own ongoing benefit programs.

Other reasons have been offered: Some candidates are unvaccinated (an immediate deal-breaker in my office), and some working parents continue to face a lack of childcare or in-person schooling for their children. Some applicants – regardless of vaccination status – have said they are hesitant to work in a medical office setting and risk getting COVID-19, despite all the precautions we have in place. Others have said they are waiting until the job market improves.

There are no easy solutions to this complicated problem, but here are a few suggestions culled from my research and conversations with HR professionals and others.

One obvious option is to offer higher wages, and perhaps even signing bonuses. “Whenever anyone says they can’t find the workers they need,” a consultant told me, “they are really saying they can’t find them at the wages they want to pay.” There are limits to the wages and benefits a private office with a very finite salary budget can offer, of course – but a few higher-paid employees may be preferable to no new workers at all.

For job candidates who fear COVID-19 exposure, assure them that their health and safety is a priority by spelling out the procedures your office is following (social distancing, reduced patient capacity, interaction barriers, face masks, avoidance of handshakes, enhanced cleaning procedures, symptom questionnaires, temperature checks, etc.) to minimize the risk of exposure.

You also may need to rework your interview process. In the Zoom era, most preliminary interviews can be conducted remotely. For on-site interviews, explain how you’re maintaining a safe interview environment by applying the same office safety policies to interactions with interviewees.

If a promising candidate doesn’t show up for an interview, the applicant could be making a token effort to obtain a job in order to perpetuate unemployment payments, but don’t jump to that conclusion. There may be extenuating circumstances, such as an emergency, illness, or traffic issues. Also, consider the possibility that it was your fault. If you waited too long to schedule the interview, another office could have lured them away. Or you may not have adequately explained your COVID-19 exposure safeguards. At the very least, a drawn-out process or a lack of transparency can make applicants apprehensive about accepting a job with you, particularly if other employers are pursuing them.

To counter the shortsighted appeal of collecting unemployment benefits, it may help to highlight the long-term growth opportunities available at your office. Consider outlining typical career tracks, or providing specific examples of how people have advanced their careers at your facility. I frequently cite the example of my current office manager, who began as an assistant receptionist almost 30 years ago.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

As private practices try to recover and rebuild in the wake of the COVID-19 pandemic, many have faced an unexpected challenge: a paucity of employees.

My own office is prime example: I have had job listings for both front- and back-office positions posted on all the major job boards and other employment portals for months, with a disappointing response. Of the few who do respond, many, incredibly, do not show up for their interviews!

It turns out that this is a widespread problem, and not just in medicine. A recent survey by the National Federation of Independent Business found that 42% of business owners, in all walks of life, had job openings that could not be filled, a record high. Over 90% of those hiring reported few or no qualified applicants and an increase in interview no-shows.

Clearly, this is a huge obstacle to growth – and even to conducting normal operations – for my practice and many others.

Reasons for the situation vary, but a big one has been the unfortunate fact that many open job positions actually pay less than the expanded unemployment benefits that many people have received under the March 2020 CARES Act. By one estimate, almost 70% of unemployed workers have been collecting more on unemployment than they earned while working. The CARES benefits expired in early September, but many potential workers continue to receive payments through a newer FEMA program, and some states have their own ongoing benefit programs.

Other reasons have been offered: Some candidates are unvaccinated (an immediate deal-breaker in my office), and some working parents continue to face a lack of childcare or in-person schooling for their children. Some applicants – regardless of vaccination status – have said they are hesitant to work in a medical office setting and risk getting COVID-19, despite all the precautions we have in place. Others have said they are waiting until the job market improves.

There are no easy solutions to this complicated problem, but here are a few suggestions culled from my research and conversations with HR professionals and others.

One obvious option is to offer higher wages, and perhaps even signing bonuses. “Whenever anyone says they can’t find the workers they need,” a consultant told me, “they are really saying they can’t find them at the wages they want to pay.” There are limits to the wages and benefits a private office with a very finite salary budget can offer, of course – but a few higher-paid employees may be preferable to no new workers at all.

For job candidates who fear COVID-19 exposure, assure them that their health and safety is a priority by spelling out the procedures your office is following (social distancing, reduced patient capacity, interaction barriers, face masks, avoidance of handshakes, enhanced cleaning procedures, symptom questionnaires, temperature checks, etc.) to minimize the risk of exposure.

You also may need to rework your interview process. In the Zoom era, most preliminary interviews can be conducted remotely. For on-site interviews, explain how you’re maintaining a safe interview environment by applying the same office safety policies to interactions with interviewees.

If a promising candidate doesn’t show up for an interview, the applicant could be making a token effort to obtain a job in order to perpetuate unemployment payments, but don’t jump to that conclusion. There may be extenuating circumstances, such as an emergency, illness, or traffic issues. Also, consider the possibility that it was your fault. If you waited too long to schedule the interview, another office could have lured them away. Or you may not have adequately explained your COVID-19 exposure safeguards. At the very least, a drawn-out process or a lack of transparency can make applicants apprehensive about accepting a job with you, particularly if other employers are pursuing them.

To counter the shortsighted appeal of collecting unemployment benefits, it may help to highlight the long-term growth opportunities available at your office. Consider outlining typical career tracks, or providing specific examples of how people have advanced their careers at your facility. I frequently cite the example of my current office manager, who began as an assistant receptionist almost 30 years ago.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

As private practices try to recover and rebuild in the wake of the COVID-19 pandemic, many have faced an unexpected challenge: a paucity of employees.

My own office is prime example: I have had job listings for both front- and back-office positions posted on all the major job boards and other employment portals for months, with a disappointing response. Of the few who do respond, many, incredibly, do not show up for their interviews!

It turns out that this is a widespread problem, and not just in medicine. A recent survey by the National Federation of Independent Business found that 42% of business owners, in all walks of life, had job openings that could not be filled, a record high. Over 90% of those hiring reported few or no qualified applicants and an increase in interview no-shows.

Clearly, this is a huge obstacle to growth – and even to conducting normal operations – for my practice and many others.

Reasons for the situation vary, but a big one has been the unfortunate fact that many open job positions actually pay less than the expanded unemployment benefits that many people have received under the March 2020 CARES Act. By one estimate, almost 70% of unemployed workers have been collecting more on unemployment than they earned while working. The CARES benefits expired in early September, but many potential workers continue to receive payments through a newer FEMA program, and some states have their own ongoing benefit programs.

Other reasons have been offered: Some candidates are unvaccinated (an immediate deal-breaker in my office), and some working parents continue to face a lack of childcare or in-person schooling for their children. Some applicants – regardless of vaccination status – have said they are hesitant to work in a medical office setting and risk getting COVID-19, despite all the precautions we have in place. Others have said they are waiting until the job market improves.

There are no easy solutions to this complicated problem, but here are a few suggestions culled from my research and conversations with HR professionals and others.

One obvious option is to offer higher wages, and perhaps even signing bonuses. “Whenever anyone says they can’t find the workers they need,” a consultant told me, “they are really saying they can’t find them at the wages they want to pay.” There are limits to the wages and benefits a private office with a very finite salary budget can offer, of course – but a few higher-paid employees may be preferable to no new workers at all.

For job candidates who fear COVID-19 exposure, assure them that their health and safety is a priority by spelling out the procedures your office is following (social distancing, reduced patient capacity, interaction barriers, face masks, avoidance of handshakes, enhanced cleaning procedures, symptom questionnaires, temperature checks, etc.) to minimize the risk of exposure.

You also may need to rework your interview process. In the Zoom era, most preliminary interviews can be conducted remotely. For on-site interviews, explain how you’re maintaining a safe interview environment by applying the same office safety policies to interactions with interviewees.

If a promising candidate doesn’t show up for an interview, the applicant could be making a token effort to obtain a job in order to perpetuate unemployment payments, but don’t jump to that conclusion. There may be extenuating circumstances, such as an emergency, illness, or traffic issues. Also, consider the possibility that it was your fault. If you waited too long to schedule the interview, another office could have lured them away. Or you may not have adequately explained your COVID-19 exposure safeguards. At the very least, a drawn-out process or a lack of transparency can make applicants apprehensive about accepting a job with you, particularly if other employers are pursuing them.

To counter the shortsighted appeal of collecting unemployment benefits, it may help to highlight the long-term growth opportunities available at your office. Consider outlining typical career tracks, or providing specific examples of how people have advanced their careers at your facility. I frequently cite the example of my current office manager, who began as an assistant receptionist almost 30 years ago.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

Persistent human papillomavirus (HPV) 16 and HPV 18 during a pregnancy may be associated with an increased risk of premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely, compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of “the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta,” said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

“The results of this study are very important in helping us understand the burden caused by HPV in pregnancy,” study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, said in an interview. “We may have just pinpointed an important cause of preterm birth that has so far been unexplained.”

Dr. Trottier and colleagues examined data from 1,052 pregnant women from three university-affiliated health care centers in Montreal between Nov. 8, 2010, and Oct. 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth, compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found 12% of those diagnosed with HPV 16 and 18 had a preterm birth, compared to 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely, compared to those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations “considered to be at low risk based on sociodemographic and sexual history characteristics,” they wrote. Dr. Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr. Trottier’s study adds to a growing body of research regarding the adverse effects of HPV, according to Dr. Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. “It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers,” Dr. Tanner said in an interview. “The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection.”

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are three HPV vaccines – 9-valent HPV vaccine (Gardasil), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix) – that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr. Trottier explained. “There is no cure when the HPV infection is present,” Dr. Trottier said. “If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women.”

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years old. However, Dr. Tanner said, women aged 27-45 who were previously unvaccinated may still receive benefit from the vaccine. 

“Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination,” Dr. Tanner explained. “This study further highlights the need to educate and encourage patients to be vaccinated.”

The researchers said future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

The experts disclosed no conflicts of interest.

Persistent human papillomavirus (HPV) 16 and HPV 18 during a pregnancy may be associated with an increased risk of premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely, compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of “the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta,” said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

“The results of this study are very important in helping us understand the burden caused by HPV in pregnancy,” study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, said in an interview. “We may have just pinpointed an important cause of preterm birth that has so far been unexplained.”

Dr. Trottier and colleagues examined data from 1,052 pregnant women from three university-affiliated health care centers in Montreal between Nov. 8, 2010, and Oct. 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth, compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found 12% of those diagnosed with HPV 16 and 18 had a preterm birth, compared to 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely, compared to those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations “considered to be at low risk based on sociodemographic and sexual history characteristics,” they wrote. Dr. Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr. Trottier’s study adds to a growing body of research regarding the adverse effects of HPV, according to Dr. Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. “It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers,” Dr. Tanner said in an interview. “The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection.”

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are three HPV vaccines – 9-valent HPV vaccine (Gardasil), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix) – that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr. Trottier explained. “There is no cure when the HPV infection is present,” Dr. Trottier said. “If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women.”

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years old. However, Dr. Tanner said, women aged 27-45 who were previously unvaccinated may still receive benefit from the vaccine. 

“Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination,” Dr. Tanner explained. “This study further highlights the need to educate and encourage patients to be vaccinated.”

The researchers said future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

The experts disclosed no conflicts of interest.

Persistent human papillomavirus (HPV) 16 and HPV 18 during a pregnancy may be associated with an increased risk of premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely, compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of “the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta,” said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

“The results of this study are very important in helping us understand the burden caused by HPV in pregnancy,” study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, said in an interview. “We may have just pinpointed an important cause of preterm birth that has so far been unexplained.”

Dr. Trottier and colleagues examined data from 1,052 pregnant women from three university-affiliated health care centers in Montreal between Nov. 8, 2010, and Oct. 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth, compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found 12% of those diagnosed with HPV 16 and 18 had a preterm birth, compared to 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely, compared to those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations “considered to be at low risk based on sociodemographic and sexual history characteristics,” they wrote. Dr. Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr. Trottier’s study adds to a growing body of research regarding the adverse effects of HPV, according to Dr. Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. “It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers,” Dr. Tanner said in an interview. “The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection.”

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are three HPV vaccines – 9-valent HPV vaccine (Gardasil), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix) – that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr. Trottier explained. “There is no cure when the HPV infection is present,” Dr. Trottier said. “If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women.”

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years old. However, Dr. Tanner said, women aged 27-45 who were previously unvaccinated may still receive benefit from the vaccine. 

“Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination,” Dr. Tanner explained. “This study further highlights the need to educate and encourage patients to be vaccinated.”

The researchers said future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

The experts disclosed no conflicts of interest.

Breast density in women aged 65 years and older may confer an increased risk of invasive breast cancer, much as it does in women aged 40-65 years, a large prospective cohort study suggests.

The findings, based on an analysis of Breast Cancer Surveillance Consortium data from Jan. 1, 1996, to Dec. 31, 2012, have potential implications for screening mammography decisions in older women – particularly those aged 75 years and older, for whom screening guidance is limited by a paucity of data, Dejana Braithwaite, PhD, of the University of Florida Health Cancer Center, Gainesville, and colleagues reported in JAMA Network Open.

The investigators analyzed 221,714 screening mammograms from 193,787 women aged 65 and older in the United States. About 65% of the mammograms were from women aged 65-74 years and about 35% were from women aged 75 years and older, who comprised 38% of the study population.

During a mean follow-up of 6.3 years, 5,069 invasive breast cancers were diagnosed, the authors noted.

The 5-year cumulative incidence of invasive breast cancer increased in tandem with increasing breast density among those aged 65-74 years and among those aged 75 and older: The cumulative incidence per 1,000 women aged 65-74 years was 11.3 for those with almost entirely fatty breasts, 17.2 for those with scattered fibroglandular densities, and 23.7 for those with extremely or heterogeneously dense breasts. The cumulative incidence rates for those aged 75 years and older were 13.5, 18.4, and 22.5 per 1,000 women, respectively, they found.

Extreme or heterogeneous breast density was associated with increased risk of breast cancer, compared with scattered fibroglandular breast density, in both age categories (hazard ratios, 1.39 and 1.23 for those aged 65-74 years and 75 years and older, respectively), whereas the risk of invasive breast cancer was about 30% lower among women with almost entirely fatty breasts, compared with women with scattered fibroglandular breast density (HRs, 0.66 and 0.73 for the 65-74 and 75-plus age groups, respectively).

The associations between breast density and breast cancer were statistically significant after adjustment for body mass index (BMI) and other risk factors.

However, no significant differences were seen between breast density and breast cancer risk based on BMI, noted the authors, who investigated this potential association as part of their effort to identify subpopulations of older women who might benefit from screening, “especially because the U.S. Preventive Service Task Force guidelines state that the current evidence is considered insufficient to recommend routine breast cancer screening for women aged 75 years or older,” they wrote.

Further, although breast density is important in risk assessment and could be evaluated in older women, some risk prediction models exclude women aged 75 or older in risk assessments, they noted, adding that this is concerning given “the aging of the population in the U.S. and worldwide.”

“The positive associations found in this study between breast density and breast cancer among women aged 75 years or older suggest that breast density and life expectancy should be considered together when discussing the potential benefits and harms of continued screening mammography in this population,” they concluded.

The new findings supplement those from prior studies and highlight “the intersection of ... two subjects that have garnered considerable lay public, healthy policy, and academic interest” in recent years: screening mammography in older women and the risk of breast cancer caused by breast density in older women, Catherine M. Tuite, MD, of ChristianaCare Helen F. Graham Cancer Center and Research Institute, Newark, Del., wrote in a commentary published with the study.

“Although there is a linear association between age and mammographic density, age is not a perfect surrogate for the latter, and there are meaningful numbers of older women with mammographically dense breast tissue,” she said, noting that a 75-year-old woman in the United States has a life expectancy of 12-14 additional years, and that “continuation of screening mammography in healthy women aged 75 years or older may offer a substantial opportunity to avoid morbidity and mortality from breast cancer in this age group.”

However, overdiagnosis also remains a concern, she said.

“Breast density and age are only a few of the many factors currently under investigation in the drive toward risk-based or personalized breast cancer screening,” she wrote. “We must remain cautious in the application of restrictive screening for women of any age with supposedly lower than average risk ... ultimately, the decision of when to stop screening is personal, and each woman deserves the agency to weigh her own wishes, values, and life experiences with an accurate and unbiased discussion of risks and benefits of screening mammography in making that decision.”

This study was supported by grants from the National Cancer Institute and the Breast Cancer Surveillance Consortium. Cancer and vital status data collection was supported in part by several state public health departments and cancer registries. Dr. Advani and Dr. Tuite each reported having no disclosures.

sworcester@mdedge.com

Breast density in women aged 65 years and older may confer an increased risk of invasive breast cancer, much as it does in women aged 40-65 years, a large prospective cohort study suggests.

The findings, based on an analysis of Breast Cancer Surveillance Consortium data from Jan. 1, 1996, to Dec. 31, 2012, have potential implications for screening mammography decisions in older women – particularly those aged 75 years and older, for whom screening guidance is limited by a paucity of data, Dejana Braithwaite, PhD, of the University of Florida Health Cancer Center, Gainesville, and colleagues reported in JAMA Network Open.

The investigators analyzed 221,714 screening mammograms from 193,787 women aged 65 and older in the United States. About 65% of the mammograms were from women aged 65-74 years and about 35% were from women aged 75 years and older, who comprised 38% of the study population.

During a mean follow-up of 6.3 years, 5,069 invasive breast cancers were diagnosed, the authors noted.

The 5-year cumulative incidence of invasive breast cancer increased in tandem with increasing breast density among those aged 65-74 years and among those aged 75 and older: The cumulative incidence per 1,000 women aged 65-74 years was 11.3 for those with almost entirely fatty breasts, 17.2 for those with scattered fibroglandular densities, and 23.7 for those with extremely or heterogeneously dense breasts. The cumulative incidence rates for those aged 75 years and older were 13.5, 18.4, and 22.5 per 1,000 women, respectively, they found.

Extreme or heterogeneous breast density was associated with increased risk of breast cancer, compared with scattered fibroglandular breast density, in both age categories (hazard ratios, 1.39 and 1.23 for those aged 65-74 years and 75 years and older, respectively), whereas the risk of invasive breast cancer was about 30% lower among women with almost entirely fatty breasts, compared with women with scattered fibroglandular breast density (HRs, 0.66 and 0.73 for the 65-74 and 75-plus age groups, respectively).

The associations between breast density and breast cancer were statistically significant after adjustment for body mass index (BMI) and other risk factors.

However, no significant differences were seen between breast density and breast cancer risk based on BMI, noted the authors, who investigated this potential association as part of their effort to identify subpopulations of older women who might benefit from screening, “especially because the U.S. Preventive Service Task Force guidelines state that the current evidence is considered insufficient to recommend routine breast cancer screening for women aged 75 years or older,” they wrote.

Further, although breast density is important in risk assessment and could be evaluated in older women, some risk prediction models exclude women aged 75 or older in risk assessments, they noted, adding that this is concerning given “the aging of the population in the U.S. and worldwide.”

“The positive associations found in this study between breast density and breast cancer among women aged 75 years or older suggest that breast density and life expectancy should be considered together when discussing the potential benefits and harms of continued screening mammography in this population,” they concluded.

The new findings supplement those from prior studies and highlight “the intersection of ... two subjects that have garnered considerable lay public, healthy policy, and academic interest” in recent years: screening mammography in older women and the risk of breast cancer caused by breast density in older women, Catherine M. Tuite, MD, of ChristianaCare Helen F. Graham Cancer Center and Research Institute, Newark, Del., wrote in a commentary published with the study.

“Although there is a linear association between age and mammographic density, age is not a perfect surrogate for the latter, and there are meaningful numbers of older women with mammographically dense breast tissue,” she said, noting that a 75-year-old woman in the United States has a life expectancy of 12-14 additional years, and that “continuation of screening mammography in healthy women aged 75 years or older may offer a substantial opportunity to avoid morbidity and mortality from breast cancer in this age group.”

However, overdiagnosis also remains a concern, she said.

“Breast density and age are only a few of the many factors currently under investigation in the drive toward risk-based or personalized breast cancer screening,” she wrote. “We must remain cautious in the application of restrictive screening for women of any age with supposedly lower than average risk ... ultimately, the decision of when to stop screening is personal, and each woman deserves the agency to weigh her own wishes, values, and life experiences with an accurate and unbiased discussion of risks and benefits of screening mammography in making that decision.”

This study was supported by grants from the National Cancer Institute and the Breast Cancer Surveillance Consortium. Cancer and vital status data collection was supported in part by several state public health departments and cancer registries. Dr. Advani and Dr. Tuite each reported having no disclosures.

sworcester@mdedge.com

Breast density in women aged 65 years and older may confer an increased risk of invasive breast cancer, much as it does in women aged 40-65 years, a large prospective cohort study suggests.

The findings, based on an analysis of Breast Cancer Surveillance Consortium data from Jan. 1, 1996, to Dec. 31, 2012, have potential implications for screening mammography decisions in older women – particularly those aged 75 years and older, for whom screening guidance is limited by a paucity of data, Dejana Braithwaite, PhD, of the University of Florida Health Cancer Center, Gainesville, and colleagues reported in JAMA Network Open.

The investigators analyzed 221,714 screening mammograms from 193,787 women aged 65 and older in the United States. About 65% of the mammograms were from women aged 65-74 years and about 35% were from women aged 75 years and older, who comprised 38% of the study population.

During a mean follow-up of 6.3 years, 5,069 invasive breast cancers were diagnosed, the authors noted.

The 5-year cumulative incidence of invasive breast cancer increased in tandem with increasing breast density among those aged 65-74 years and among those aged 75 and older: The cumulative incidence per 1,000 women aged 65-74 years was 11.3 for those with almost entirely fatty breasts, 17.2 for those with scattered fibroglandular densities, and 23.7 for those with extremely or heterogeneously dense breasts. The cumulative incidence rates for those aged 75 years and older were 13.5, 18.4, and 22.5 per 1,000 women, respectively, they found.

Extreme or heterogeneous breast density was associated with increased risk of breast cancer, compared with scattered fibroglandular breast density, in both age categories (hazard ratios, 1.39 and 1.23 for those aged 65-74 years and 75 years and older, respectively), whereas the risk of invasive breast cancer was about 30% lower among women with almost entirely fatty breasts, compared with women with scattered fibroglandular breast density (HRs, 0.66 and 0.73 for the 65-74 and 75-plus age groups, respectively).

The associations between breast density and breast cancer were statistically significant after adjustment for body mass index (BMI) and other risk factors.

However, no significant differences were seen between breast density and breast cancer risk based on BMI, noted the authors, who investigated this potential association as part of their effort to identify subpopulations of older women who might benefit from screening, “especially because the U.S. Preventive Service Task Force guidelines state that the current evidence is considered insufficient to recommend routine breast cancer screening for women aged 75 years or older,” they wrote.

Further, although breast density is important in risk assessment and could be evaluated in older women, some risk prediction models exclude women aged 75 or older in risk assessments, they noted, adding that this is concerning given “the aging of the population in the U.S. and worldwide.”

“The positive associations found in this study between breast density and breast cancer among women aged 75 years or older suggest that breast density and life expectancy should be considered together when discussing the potential benefits and harms of continued screening mammography in this population,” they concluded.

The new findings supplement those from prior studies and highlight “the intersection of ... two subjects that have garnered considerable lay public, healthy policy, and academic interest” in recent years: screening mammography in older women and the risk of breast cancer caused by breast density in older women, Catherine M. Tuite, MD, of ChristianaCare Helen F. Graham Cancer Center and Research Institute, Newark, Del., wrote in a commentary published with the study.

“Although there is a linear association between age and mammographic density, age is not a perfect surrogate for the latter, and there are meaningful numbers of older women with mammographically dense breast tissue,” she said, noting that a 75-year-old woman in the United States has a life expectancy of 12-14 additional years, and that “continuation of screening mammography in healthy women aged 75 years or older may offer a substantial opportunity to avoid morbidity and mortality from breast cancer in this age group.”

However, overdiagnosis also remains a concern, she said.

“Breast density and age are only a few of the many factors currently under investigation in the drive toward risk-based or personalized breast cancer screening,” she wrote. “We must remain cautious in the application of restrictive screening for women of any age with supposedly lower than average risk ... ultimately, the decision of when to stop screening is personal, and each woman deserves the agency to weigh her own wishes, values, and life experiences with an accurate and unbiased discussion of risks and benefits of screening mammography in making that decision.”

This study was supported by grants from the National Cancer Institute and the Breast Cancer Surveillance Consortium. Cancer and vital status data collection was supported in part by several state public health departments and cancer registries. Dr. Advani and Dr. Tuite each reported having no disclosures.

sworcester@mdedge.com

If you haven’t noticed yet, there has been an explosion of new online companies specializing in slicing off some little sliver of health care and leaving traditional medicine to take care of the rest of the patient. Lately, many of these startups involve mental health care, traditionally a difficult area to make profitable unless one caters just to the wealthy. Many pediatricians have been unsure exactly what to make of these new efforts. Are these the rescuers we’ve been waiting for to fill what seems like an enormous and growing unmet need? Are they just another means to extract money from desperate people and leave the real work to someone else? Something in-between? This article outlines some points to consider when evaluating this new frontier.

Case vignette

A 12-year-old girl presents with her parents for an annual exam. She has been struggling with her mood and anxiety over the past 2 years along with occasional superficial cutting. You have started treatment with a selective serotonin reuptake inhibitor and have recommended that she see a mental health professional but the parents report that one attempt with a therapist was a poor fit and nobody in the area seems to be accepting new patients. The parents state that they saw an advertisement on TV for a company that offers online psychotherapy by video appointments or text. They think this might be an option to pursue but are a little skeptical of the whole idea. They look for your opinion on this topic.

Most of these companies operate by having subscribers pay a monthly fee for different levels of services such as videoconference therapy sessions, supportive text messages, or even some psychopharmacological care. Many also offer the ability to switch rapidly between clinicians if you don’t like the one you have.

These arrangements sound great as the world grows increasingly comfortable with online communication and the mental health needs of children and adolescents increase with the seemingly endless COVID pandemic. Further, research generally finds that online mental health treatment is just as effective as services delivered in person, although the data on therapy by text are less robust.

Nevertheless, a lot of skepticism remains about online mental health treatment, particularly among those involved in more traditionally delivered mental health care. Some of the concerns that often get brought up include the following:
 

• Cost. Most of these online groups, especially the big national companies, don’t interact directly with insurance companies, leaving a lot of out-of-pocket expenses or the need for families to work things out directly with their insurance provider.
• Care fragmentation. In many ways, the online mental health care surge seems at odds with the growing “integrated care” movement that is trying to embed more behavioral care within primary care practices. From this lens, outsourcing someone’s mental health treatment to a therapist across the country that the patient has never actually met seems like a step in the wrong direction. Further, concerns arise about how much these folks will know about local resources in the community.
• The corporate model in mental health care. While being able to shop for a therapist like you would for a pillow sounds great on the surface, there are many times where a patient may need to be supportively confronted by their therapist or told no when asking about things like certain medications. The “customer is always right” principle often falls short when it comes to good mental health treatment.
• Depth and type of treatment. It is probably fair to say that most online therapy could be described as supportive psychotherapy. This type of therapy can be quite helpful for many but may lack the depth or specific techniques that some people need. For youth, some of the most effective types of psychotherapy, like cognitive-behavioral therapy (CBT), can be harder to find, and implement, online.
• Emergencies. While many online companies claim to offer round-the-clock support for paying customers, they can quickly punt to “call your doctor” or even “call 911” if there is any real mental health crisis.

Balancing these potential benefits and pitfalls of online therapy, here are a few questions your patients may want to consider before signing onto a long-term contract with an online therapy company.

• Would the online clinician have any knowledge of my community? In some cases, this may not matter that much, while for others it could be quite important.
• What happens in an emergency? Would the regular online therapist be available to help through a crisis or would things revert back to local resources?
• What about privacy and collaboration? Effective communication between a patient’s primary care clinician and their therapist can be crucial to good care, and asking the patient always to be the intermediary can be fraught with difficulty.
• How long is the contract? Just like those gym memberships, these companies bank on individuals who sign up but then don’t really use the service.
• What kind of training do the therapists at the site have? Is it possible to receive specific types of therapy, like CBT or parent training? Otherwise, pediatricians might be quite likely to hear back from the family wondering about medications after therapy “isn’t helping.”

Overall, mental health treatment delivered by telehealth is here to stay whether we like it or not. For some families, it is likely to provide new access to services not easily obtainable locally, while for others it could end up being a costly and ineffective enterprise. For families who use these services, a key challenge for pediatricians that may be important to overcome is finding a way for these clinicians to integrate into the overall medical team rather than being a detached island unto themselves.
 

Dr. Rettew is a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. His book, “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood” (New York: Oxford University Press, 2021). Email him at pdnews@mdedge.com.

If you haven’t noticed yet, there has been an explosion of new online companies specializing in slicing off some little sliver of health care and leaving traditional medicine to take care of the rest of the patient. Lately, many of these startups involve mental health care, traditionally a difficult area to make profitable unless one caters just to the wealthy. Many pediatricians have been unsure exactly what to make of these new efforts. Are these the rescuers we’ve been waiting for to fill what seems like an enormous and growing unmet need? Are they just another means to extract money from desperate people and leave the real work to someone else? Something in-between? This article outlines some points to consider when evaluating this new frontier.

Case vignette

A 12-year-old girl presents with her parents for an annual exam. She has been struggling with her mood and anxiety over the past 2 years along with occasional superficial cutting. You have started treatment with a selective serotonin reuptake inhibitor and have recommended that she see a mental health professional but the parents report that one attempt with a therapist was a poor fit and nobody in the area seems to be accepting new patients. The parents state that they saw an advertisement on TV for a company that offers online psychotherapy by video appointments or text. They think this might be an option to pursue but are a little skeptical of the whole idea. They look for your opinion on this topic.

Most of these companies operate by having subscribers pay a monthly fee for different levels of services such as videoconference therapy sessions, supportive text messages, or even some psychopharmacological care. Many also offer the ability to switch rapidly between clinicians if you don’t like the one you have.

These arrangements sound great as the world grows increasingly comfortable with online communication and the mental health needs of children and adolescents increase with the seemingly endless COVID pandemic. Further, research generally finds that online mental health treatment is just as effective as services delivered in person, although the data on therapy by text are less robust.

Nevertheless, a lot of skepticism remains about online mental health treatment, particularly among those involved in more traditionally delivered mental health care. Some of the concerns that often get brought up include the following:
 

• Cost. Most of these online groups, especially the big national companies, don’t interact directly with insurance companies, leaving a lot of out-of-pocket expenses or the need for families to work things out directly with their insurance provider.
• Care fragmentation. In many ways, the online mental health care surge seems at odds with the growing “integrated care” movement that is trying to embed more behavioral care within primary care practices. From this lens, outsourcing someone’s mental health treatment to a therapist across the country that the patient has never actually met seems like a step in the wrong direction. Further, concerns arise about how much these folks will know about local resources in the community.
• The corporate model in mental health care. While being able to shop for a therapist like you would for a pillow sounds great on the surface, there are many times where a patient may need to be supportively confronted by their therapist or told no when asking about things like certain medications. The “customer is always right” principle often falls short when it comes to good mental health treatment.
• Depth and type of treatment. It is probably fair to say that most online therapy could be described as supportive psychotherapy. This type of therapy can be quite helpful for many but may lack the depth or specific techniques that some people need. For youth, some of the most effective types of psychotherapy, like cognitive-behavioral therapy (CBT), can be harder to find, and implement, online.
• Emergencies. While many online companies claim to offer round-the-clock support for paying customers, they can quickly punt to “call your doctor” or even “call 911” if there is any real mental health crisis.

Balancing these potential benefits and pitfalls of online therapy, here are a few questions your patients may want to consider before signing onto a long-term contract with an online therapy company.

• Would the online clinician have any knowledge of my community? In some cases, this may not matter that much, while for others it could be quite important.
• What happens in an emergency? Would the regular online therapist be available to help through a crisis or would things revert back to local resources?
• What about privacy and collaboration? Effective communication between a patient’s primary care clinician and their therapist can be crucial to good care, and asking the patient always to be the intermediary can be fraught with difficulty.
• How long is the contract? Just like those gym memberships, these companies bank on individuals who sign up but then don’t really use the service.
• What kind of training do the therapists at the site have? Is it possible to receive specific types of therapy, like CBT or parent training? Otherwise, pediatricians might be quite likely to hear back from the family wondering about medications after therapy “isn’t helping.”

Overall, mental health treatment delivered by telehealth is here to stay whether we like it or not. For some families, it is likely to provide new access to services not easily obtainable locally, while for others it could end up being a costly and ineffective enterprise. For families who use these services, a key challenge for pediatricians that may be important to overcome is finding a way for these clinicians to integrate into the overall medical team rather than being a detached island unto themselves.
 

Dr. Rettew is a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. His book, “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood” (New York: Oxford University Press, 2021). Email him at pdnews@mdedge.com.

If you haven’t noticed yet, there has been an explosion of new online companies specializing in slicing off some little sliver of health care and leaving traditional medicine to take care of the rest of the patient. Lately, many of these startups involve mental health care, traditionally a difficult area to make profitable unless one caters just to the wealthy. Many pediatricians have been unsure exactly what to make of these new efforts. Are these the rescuers we’ve been waiting for to fill what seems like an enormous and growing unmet need? Are they just another means to extract money from desperate people and leave the real work to someone else? Something in-between? This article outlines some points to consider when evaluating this new frontier.

Case vignette

A 12-year-old girl presents with her parents for an annual exam. She has been struggling with her mood and anxiety over the past 2 years along with occasional superficial cutting. You have started treatment with a selective serotonin reuptake inhibitor and have recommended that she see a mental health professional but the parents report that one attempt with a therapist was a poor fit and nobody in the area seems to be accepting new patients. The parents state that they saw an advertisement on TV for a company that offers online psychotherapy by video appointments or text. They think this might be an option to pursue but are a little skeptical of the whole idea. They look for your opinion on this topic.

Most of these companies operate by having subscribers pay a monthly fee for different levels of services such as videoconference therapy sessions, supportive text messages, or even some psychopharmacological care. Many also offer the ability to switch rapidly between clinicians if you don’t like the one you have.

These arrangements sound great as the world grows increasingly comfortable with online communication and the mental health needs of children and adolescents increase with the seemingly endless COVID pandemic. Further, research generally finds that online mental health treatment is just as effective as services delivered in person, although the data on therapy by text are less robust.

Nevertheless, a lot of skepticism remains about online mental health treatment, particularly among those involved in more traditionally delivered mental health care. Some of the concerns that often get brought up include the following:
 

• Cost. Most of these online groups, especially the big national companies, don’t interact directly with insurance companies, leaving a lot of out-of-pocket expenses or the need for families to work things out directly with their insurance provider.
• Care fragmentation. In many ways, the online mental health care surge seems at odds with the growing “integrated care” movement that is trying to embed more behavioral care within primary care practices. From this lens, outsourcing someone’s mental health treatment to a therapist across the country that the patient has never actually met seems like a step in the wrong direction. Further, concerns arise about how much these folks will know about local resources in the community.
• The corporate model in mental health care. While being able to shop for a therapist like you would for a pillow sounds great on the surface, there are many times where a patient may need to be supportively confronted by their therapist or told no when asking about things like certain medications. The “customer is always right” principle often falls short when it comes to good mental health treatment.
• Depth and type of treatment. It is probably fair to say that most online therapy could be described as supportive psychotherapy. This type of therapy can be quite helpful for many but may lack the depth or specific techniques that some people need. For youth, some of the most effective types of psychotherapy, like cognitive-behavioral therapy (CBT), can be harder to find, and implement, online.
• Emergencies. While many online companies claim to offer round-the-clock support for paying customers, they can quickly punt to “call your doctor” or even “call 911” if there is any real mental health crisis.

Balancing these potential benefits and pitfalls of online therapy, here are a few questions your patients may want to consider before signing onto a long-term contract with an online therapy company.

• Would the online clinician have any knowledge of my community? In some cases, this may not matter that much, while for others it could be quite important.
• What happens in an emergency? Would the regular online therapist be available to help through a crisis or would things revert back to local resources?
• What about privacy and collaboration? Effective communication between a patient’s primary care clinician and their therapist can be crucial to good care, and asking the patient always to be the intermediary can be fraught with difficulty.
• How long is the contract? Just like those gym memberships, these companies bank on individuals who sign up but then don’t really use the service.
• What kind of training do the therapists at the site have? Is it possible to receive specific types of therapy, like CBT or parent training? Otherwise, pediatricians might be quite likely to hear back from the family wondering about medications after therapy “isn’t helping.”

Overall, mental health treatment delivered by telehealth is here to stay whether we like it or not. For some families, it is likely to provide new access to services not easily obtainable locally, while for others it could end up being a costly and ineffective enterprise. For families who use these services, a key challenge for pediatricians that may be important to overcome is finding a way for these clinicians to integrate into the overall medical team rather than being a detached island unto themselves.
 

Dr. Rettew is a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. His book, “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood” (New York: Oxford University Press, 2021). Email him at pdnews@mdedge.com.

Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving,” said Dr. Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.

A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
 

Better documentation needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.

“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”

Dr. Gold had no relevant financial disclosures.

Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving,” said Dr. Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.

A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
 

Better documentation needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.

“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”

Dr. Gold had no relevant financial disclosures.

Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving,” said Dr. Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.

A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
 

Better documentation needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.

“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”

Dr. Gold had no relevant financial disclosures.

In the clinical opinion of Alex G. Ortega-Loayza, MD, MCR, few absolutes drive the initial assessment of patients who present with skin ulcers.

While lower-extremity ulcers stem from vascular, neuropathic, or pressure-related causes in about 70% of cases, an estimated 20% of cases are atypical, and another 10% are inconclusive. The causes can be neoplastic, infectious, inflammatory, vasculopathic, external, and genetic. “Sometimes they can be of mixed etiology, which make them even more complicated to heal,” Dr. Ortega-Loayza, of the department of dermatology at Oregon Health & Science University, Portland, said during the annual meeting of the Pacific Dermatologic Association.

In a study published in 2019, he and his colleagues at four academic hospitals evaluated characteristics and diagnoses of ulcers in 274 patients with skin ulcers in inpatient dermatology consultation services between July 2015 and July 2018. Most primary teams requesting the consultation (93%) were from nonsurgical specialties. The median age of these patients was 54 years, 45% were male, and 50% had lower-extremity ulcers. Nearly two-thirds of the ulcers (62%) were chronic in nature, while the remaining 38% were acute. The skin ulcer was the chief reason for admission in 49% of cases and 66% were admitted through the ED. In addition, 11% had a superinfected skin ulcer.

The top three etiologies rendered by dermatologists after assessing these patients were pyoderma gangrenosum (17%), infection (13%), and exogenous causes (12%); another 12% remained diagnostically inconclusive after consultation. Diagnostic agreements between the primary team requesting the consultation and the dermatologist were poor to modest.

These data highlights the role of the dermatologists in the workup of skin ulcers of unknown etiology.

“The diagnosis of skin ulcers can be challenging,” Dr. Ortega-Loayza said. “Subjective factors playing a role in the diagnosis of skin ulcers include the type of level of training/experience you’ve had and general awareness and education about skin ulcers.” In addition, there is also a lack of gold-standard diagnostic criteria for atypical/inflammatory ulcers and a lack of specificity of ancillary testing, such as for pyoderma gangrenosum.

Dr. Ortega-Loayza’s basic workup is based on the review of systems and the patient’s comorbidities. Blood work may include CBC, comprehensive metabolic panel, erythrocyte sedimentation rate/C-reactive protein, glucose-6-phosphate dehydrogenase, albumin/prealbumin, autoimmune panels, and hypercoagulable panels. He may order a skin biopsy with H&E staining and microbiological studies, superficial bacterial wound cultures, and vascular studies, such as ankle brachial index (ABI) and chronic venous reflux tests, and Doppler ultrasound, and he might consider an angiogram for certain type of ulcers. Additional imaging studies may include x-ray, CT scan, and/or MRI.

The four key factors to control in patients with skin ulcers, he continued, include effective management of edema (such as compression garments depending on the results of the vascular studies); infection (with topical/oral antibiotics and debridement); the wound microenvironment (with wound dressings), and pain (mainly with nonopioids). “In my practice, we tend to do multilayered compression,” he said. “This can be two- or four-layer. I do light compression if the patient has peripheral arterial disease. I always bring in the patient 2 days later to check on them, or do a telehealth visit, to make sure they are not developing any worsening of the ulcers.”

Infections can be managed with topical antimicrobials such as metronidazole 1% gel and cadexomer iodine. “Iodine can also help dry the wound when you need to do so,” said Dr. Ortega-Loayza, who directs a pyoderma gangrenosum clinic at OHSU. “Debridement can be done with a curette or with commercially available enzymatic products such as Collagenase, PluroGel, and MediHoney.”

When the ulcer is in an active phase (characterized by significant amount of drainage and erythema), he uses one or more of the following products to control the wound microenvironment: zinc oxide, an antimicrobial dressing, a hyperabsorbent dressing, an abdominal pad, and compression.

During the healing phase, with evidence of re-epithelization, he tends to use more foam dressings and continues with compression. His preferred options for managing pain associated with ulcers are medications to control neuropathic pain including initially gabapentin (100 mg-300 mg at bedtime), pregabalin (75 mg twice a day), or duloxetine (extended release, 30 mg once a day). All of these medications can be titrated up based on patients’ needs. Foam dressings with ibuprofen can also provide comfort, he said.

Dr. Ortega-Loayza also provided a few clinical pearls highlighting the role and utility of interleukin-23 inhibitors in the management of patients with pyoderma gangrenosum, oral vitamin K in patients with calciphylaxis, and stanozolol for lipodermatosclerosis. He is also leading the first open-label trial testing a Janus kinase inhibitor – baricitinib – as a treatment for patients with pyoderma gangrenosum.

Dr. Ortega-Loayza disclosed that he is a consultant to Genentech and Guidepoint and is a member of the advisory board for Bristol-Myers Squibb, Boehringer Ingelheim, and Janssen. He also has received research support from Lilly.

dbrunk@mdedge.com

In the clinical opinion of Alex G. Ortega-Loayza, MD, MCR, few absolutes drive the initial assessment of patients who present with skin ulcers.

While lower-extremity ulcers stem from vascular, neuropathic, or pressure-related causes in about 70% of cases, an estimated 20% of cases are atypical, and another 10% are inconclusive. The causes can be neoplastic, infectious, inflammatory, vasculopathic, external, and genetic. “Sometimes they can be of mixed etiology, which make them even more complicated to heal,” Dr. Ortega-Loayza, of the department of dermatology at Oregon Health & Science University, Portland, said during the annual meeting of the Pacific Dermatologic Association.

In a study published in 2019, he and his colleagues at four academic hospitals evaluated characteristics and diagnoses of ulcers in 274 patients with skin ulcers in inpatient dermatology consultation services between July 2015 and July 2018. Most primary teams requesting the consultation (93%) were from nonsurgical specialties. The median age of these patients was 54 years, 45% were male, and 50% had lower-extremity ulcers. Nearly two-thirds of the ulcers (62%) were chronic in nature, while the remaining 38% were acute. The skin ulcer was the chief reason for admission in 49% of cases and 66% were admitted through the ED. In addition, 11% had a superinfected skin ulcer.

The top three etiologies rendered by dermatologists after assessing these patients were pyoderma gangrenosum (17%), infection (13%), and exogenous causes (12%); another 12% remained diagnostically inconclusive after consultation. Diagnostic agreements between the primary team requesting the consultation and the dermatologist were poor to modest.

These data highlights the role of the dermatologists in the workup of skin ulcers of unknown etiology.

“The diagnosis of skin ulcers can be challenging,” Dr. Ortega-Loayza said. “Subjective factors playing a role in the diagnosis of skin ulcers include the type of level of training/experience you’ve had and general awareness and education about skin ulcers.” In addition, there is also a lack of gold-standard diagnostic criteria for atypical/inflammatory ulcers and a lack of specificity of ancillary testing, such as for pyoderma gangrenosum.

Dr. Ortega-Loayza’s basic workup is based on the review of systems and the patient’s comorbidities. Blood work may include CBC, comprehensive metabolic panel, erythrocyte sedimentation rate/C-reactive protein, glucose-6-phosphate dehydrogenase, albumin/prealbumin, autoimmune panels, and hypercoagulable panels. He may order a skin biopsy with H&E staining and microbiological studies, superficial bacterial wound cultures, and vascular studies, such as ankle brachial index (ABI) and chronic venous reflux tests, and Doppler ultrasound, and he might consider an angiogram for certain type of ulcers. Additional imaging studies may include x-ray, CT scan, and/or MRI.

The four key factors to control in patients with skin ulcers, he continued, include effective management of edema (such as compression garments depending on the results of the vascular studies); infection (with topical/oral antibiotics and debridement); the wound microenvironment (with wound dressings), and pain (mainly with nonopioids). “In my practice, we tend to do multilayered compression,” he said. “This can be two- or four-layer. I do light compression if the patient has peripheral arterial disease. I always bring in the patient 2 days later to check on them, or do a telehealth visit, to make sure they are not developing any worsening of the ulcers.”

Infections can be managed with topical antimicrobials such as metronidazole 1% gel and cadexomer iodine. “Iodine can also help dry the wound when you need to do so,” said Dr. Ortega-Loayza, who directs a pyoderma gangrenosum clinic at OHSU. “Debridement can be done with a curette or with commercially available enzymatic products such as Collagenase, PluroGel, and MediHoney.”

When the ulcer is in an active phase (characterized by significant amount of drainage and erythema), he uses one or more of the following products to control the wound microenvironment: zinc oxide, an antimicrobial dressing, a hyperabsorbent dressing, an abdominal pad, and compression.

During the healing phase, with evidence of re-epithelization, he tends to use more foam dressings and continues with compression. His preferred options for managing pain associated with ulcers are medications to control neuropathic pain including initially gabapentin (100 mg-300 mg at bedtime), pregabalin (75 mg twice a day), or duloxetine (extended release, 30 mg once a day). All of these medications can be titrated up based on patients’ needs. Foam dressings with ibuprofen can also provide comfort, he said.

Dr. Ortega-Loayza also provided a few clinical pearls highlighting the role and utility of interleukin-23 inhibitors in the management of patients with pyoderma gangrenosum, oral vitamin K in patients with calciphylaxis, and stanozolol for lipodermatosclerosis. He is also leading the first open-label trial testing a Janus kinase inhibitor – baricitinib – as a treatment for patients with pyoderma gangrenosum.

Dr. Ortega-Loayza disclosed that he is a consultant to Genentech and Guidepoint and is a member of the advisory board for Bristol-Myers Squibb, Boehringer Ingelheim, and Janssen. He also has received research support from Lilly.

dbrunk@mdedge.com

In the clinical opinion of Alex G. Ortega-Loayza, MD, MCR, few absolutes drive the initial assessment of patients who present with skin ulcers.

While lower-extremity ulcers stem from vascular, neuropathic, or pressure-related causes in about 70% of cases, an estimated 20% of cases are atypical, and another 10% are inconclusive. The causes can be neoplastic, infectious, inflammatory, vasculopathic, external, and genetic. “Sometimes they can be of mixed etiology, which make them even more complicated to heal,” Dr. Ortega-Loayza, of the department of dermatology at Oregon Health & Science University, Portland, said during the annual meeting of the Pacific Dermatologic Association.

In a study published in 2019, he and his colleagues at four academic hospitals evaluated characteristics and diagnoses of ulcers in 274 patients with skin ulcers in inpatient dermatology consultation services between July 2015 and July 2018. Most primary teams requesting the consultation (93%) were from nonsurgical specialties. The median age of these patients was 54 years, 45% were male, and 50% had lower-extremity ulcers. Nearly two-thirds of the ulcers (62%) were chronic in nature, while the remaining 38% were acute. The skin ulcer was the chief reason for admission in 49% of cases and 66% were admitted through the ED. In addition, 11% had a superinfected skin ulcer.

The top three etiologies rendered by dermatologists after assessing these patients were pyoderma gangrenosum (17%), infection (13%), and exogenous causes (12%); another 12% remained diagnostically inconclusive after consultation. Diagnostic agreements between the primary team requesting the consultation and the dermatologist were poor to modest.

These data highlights the role of the dermatologists in the workup of skin ulcers of unknown etiology.

“The diagnosis of skin ulcers can be challenging,” Dr. Ortega-Loayza said. “Subjective factors playing a role in the diagnosis of skin ulcers include the type of level of training/experience you’ve had and general awareness and education about skin ulcers.” In addition, there is also a lack of gold-standard diagnostic criteria for atypical/inflammatory ulcers and a lack of specificity of ancillary testing, such as for pyoderma gangrenosum.

Dr. Ortega-Loayza’s basic workup is based on the review of systems and the patient’s comorbidities. Blood work may include CBC, comprehensive metabolic panel, erythrocyte sedimentation rate/C-reactive protein, glucose-6-phosphate dehydrogenase, albumin/prealbumin, autoimmune panels, and hypercoagulable panels. He may order a skin biopsy with H&E staining and microbiological studies, superficial bacterial wound cultures, and vascular studies, such as ankle brachial index (ABI) and chronic venous reflux tests, and Doppler ultrasound, and he might consider an angiogram for certain type of ulcers. Additional imaging studies may include x-ray, CT scan, and/or MRI.

The four key factors to control in patients with skin ulcers, he continued, include effective management of edema (such as compression garments depending on the results of the vascular studies); infection (with topical/oral antibiotics and debridement); the wound microenvironment (with wound dressings), and pain (mainly with nonopioids). “In my practice, we tend to do multilayered compression,” he said. “This can be two- or four-layer. I do light compression if the patient has peripheral arterial disease. I always bring in the patient 2 days later to check on them, or do a telehealth visit, to make sure they are not developing any worsening of the ulcers.”

Infections can be managed with topical antimicrobials such as metronidazole 1% gel and cadexomer iodine. “Iodine can also help dry the wound when you need to do so,” said Dr. Ortega-Loayza, who directs a pyoderma gangrenosum clinic at OHSU. “Debridement can be done with a curette or with commercially available enzymatic products such as Collagenase, PluroGel, and MediHoney.”

When the ulcer is in an active phase (characterized by significant amount of drainage and erythema), he uses one or more of the following products to control the wound microenvironment: zinc oxide, an antimicrobial dressing, a hyperabsorbent dressing, an abdominal pad, and compression.

During the healing phase, with evidence of re-epithelization, he tends to use more foam dressings and continues with compression. His preferred options for managing pain associated with ulcers are medications to control neuropathic pain including initially gabapentin (100 mg-300 mg at bedtime), pregabalin (75 mg twice a day), or duloxetine (extended release, 30 mg once a day). All of these medications can be titrated up based on patients’ needs. Foam dressings with ibuprofen can also provide comfort, he said.

Dr. Ortega-Loayza also provided a few clinical pearls highlighting the role and utility of interleukin-23 inhibitors in the management of patients with pyoderma gangrenosum, oral vitamin K in patients with calciphylaxis, and stanozolol for lipodermatosclerosis. He is also leading the first open-label trial testing a Janus kinase inhibitor – baricitinib – as a treatment for patients with pyoderma gangrenosum.

Dr. Ortega-Loayza disclosed that he is a consultant to Genentech and Guidepoint and is a member of the advisory board for Bristol-Myers Squibb, Boehringer Ingelheim, and Janssen. He also has received research support from Lilly.

dbrunk@mdedge.com

In 1950, at Staten Island’s Sea View Hospital, a group of patients with terminal tuberculosis were given a new antibiotic called isoniazid, which caused some unexpected side effects. The patients reported euphoria, mental stimulation, and improved sleep, and even began socializing with more vigor. The press was all over the case, writing about the sick “dancing in the halls tho’ they had holes in their lungs.” Soon doctors started prescribing isoniazid as the first-ever antidepressant.

ChrisChrisW/iStock/Getty Images

The Sea View Hospital experiment was an early hint that changing the composition of the gut microbiome – in this case, via antibiotics – might affect our mental health. Yet only in the last 2 decades has research into connections between what we ingest and psychiatric disorders really taken off. In 2004, a landmark study showed that germ-free mice (born in such sterile conditions that they lacked a microbiome) had an exaggerated stress response. The effects were reversed, however, if the mice were fed a bacterial strain, Bifidobacterium infantis, a probiotic. This sparked academic interest, and thousands of research papers followed.

According to Stephen Ilardi, PhD, a clinical psychologist at the University of Kansas, Lawrence, focusing on the etiology and treatment of depression, now is the “time of exciting discovery” in the field of probiotics and psychiatric disorders, although, admittedly, a lot still remains unknown.
 

Gut microbiome profiles in mental health disorders

We humans have about 100 trillion microbes residing in our guts. Some of these are archaea, some fungi, some protozoans and even viruses, but most are bacteria. Things like diet, sleep, and stress can all impact the composition of our gut microbiome. When the microbiome differs considerably from the typical, doctors and researchers describe it as dysbiosis, or imbalance. Studies have uncovered dysbiosis in patients with depression, anxiety, schizophrenia, and bipolar disorder.

“I think there is now pretty good evidence that the gut microbiome is actually an important factor in a number of psychiatric disorders,” says Allan Young, MBChB, clinical psychiatrist at King’s College London. The gut microbiome composition does seem to differ between psychiatric patients and the healthy. In depression, for example, a recent review of nine studies found an increase on the genus level in Streptococcus and Oscillibacter and low abundance of Lactobacillus and Coprococcus, among others. In generalized anxiety disorder, meanwhile, there appears to be an increase in Fusobacteria and Escherichia/Shigella .

For Dr. Ilardi, the next important question is whether there are plausible mechanisms that could explain how gut microbiota may influence brain function. And, it appears there are.

“The microbes in the gut can release neurotransmitters into blood that cross into the brain and influence brain function. They can release hormones into the blood that again cross into the brain. They’ve got a lot of tricks up their sleeve,” he says.

One particularly important pathway runs through the vagus nerve – the longest nerve that emerges directly from the brain, connecting it to the gut. Another is the immune pathway. Gut bacteria can interact with immune cells and reduce cytokine production, which in turn can reduce systemic inflammation. Inflammatory processes have been implicated in both depression and bipolar disorder. What’s more, gut microbes can upregulate the expression of a protein called BDNF – brain-derived neurotrophic factor – which helps the development and survival of nerve cells in the brain.
 

Probiotics’ promise varies for different conditions

As the pathways by which gut dysbiosis may influence psychiatric disorders become clearer, the next logical step is to try to influence the composition of the microbiome to prevent and treat depression, anxiety, or schizophrenia. That’s where probiotics come in.

The evidence for the effects of probiotics – live microorganisms which, when ingested in adequate amounts, confer a health benefit – so far is the strongest for depression, says Viktoriya Nikolova, MRes, MSc, a PhD student and researcher at King’s College London. In their 2021 meta-analysis of seven trials, Mr. Nikolova and colleagues revealed that probiotics can significantly reduce depressive symptoms after just 8 weeks. There was a caveat, however – the probiotics only worked when used in addition to an approved antidepressant. Another meta-analysis, published in 2018, also showed that probiotics, when compared with placebo, improve mood in people with depressive symptoms (here, no antidepressant treatment was necessary).

Roumen Milev, MD, PhD, a neuroscientist at Queen’s University, Kingston, Ont., and coauthor of a review on probiotics and depression published in the Annals of General Psychiatry, warns, however, that the research is still in its infancy. “Currently, the probiotics should be used concomitant with antidepressant treatment,” he says.

When it comes to using probiotics to relieve anxiety, “the evidence in the animal literature is really compelling,” says Dr. Ilardi. Human studies are less convincing, however, which Dr. Dr. Ilardi showed in his 2018 review and meta-analysis involving 743 animals and 1,527 humans. “Studies are small for the most part, and some of them aren’t terribly well conducted, and they often use very low doses of probiotics,” he says. One of the larger double-blind and placebo-controlled trials showed that supplementation with Lactobacillus plantarum helps reduce stress and anxiety, while the levels of proinflammatory cytokines go down. Another meta-analysis, published in June, revealed that, when it comes to reducing stress and anxiety in youth, the results are mixed.

Evidence of probiotics’ efficiency in schizophrenia is emerging, yet also limited. A 2019 review concluded that currently available results only “hint” at a possibility that probiotics could make a difference in schizophrenia. Similarly, a 2020 review summed up that the role of probiotics in bipolar disorder “remains unclear and underexplored.”
 

Better studies, remaining questions

Apart from small samples, one issue with research on probiotics is that they generally tend to use varied doses of different strains of bacteria, or even multistrain mixtures, making it tough to compare results. Although there are hundreds of species of bacteria in the human gut, only a few have been evaluated for their antidepressant or antianxiety effects.

“To make it even worse, it’s almost certainly the case that depending on a person’s actual genetics or maybe their epigenetics, a strain that is helpful for one person may not be helpful for another. There is almost certainly no one-size-fits-all probiotic formulation,” says Dr. Ilardi.

Another critical question that remains to be answered is that of potential side effects.

“Probiotics are often seen as food supplements, so they don’t follow under the same regulations as drugs would,” says Mr. Nikolova. “They don’t necessarily have to follow the pattern of drug trials in many countries, which means that the monitoring of side effects is not the requirement.”

That’s something that worries King’s College psychiatrist Young too. “If you are giving it to modulate how the brain works, you could potentially induce psychiatric symptoms or a psychiatric disorder. There could be allergic reactions. There could be lots of different things,” he says.

When you search the web for “probiotics,” chances are you will come across sites boasting amazing effects that such products can have on cardiovascular heath, the immune system, and yes, mental well-being. Many also sell various probiotic supplements “formulated” for your gut health or improved moods. However, many such commercially available strains have never been actually tested in clinical trials. What’s more, according to Kathrin Cohen Kadosh, PhD, a neuroscientist at University of Surrey (England), “it is not always clear whether the different strains actually reach the gut intact.”

For now, considering the limited research evidence, a safer bet is to try to improve gut health through consumption of fermented foods that naturally contain probiotics, such as miso, kefir, or sauerkraut. Alternatively, you could reach for prebiotics, such as foods containing fiber (prebiotics enhance the growth of beneficial gut microbes). This, Dr. Kadosh says, could be “a gentler way of improving gut health” than popping a pill. Whether an improved mental well-being might follow still remains to be seen.

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

In 1950, at Staten Island’s Sea View Hospital, a group of patients with terminal tuberculosis were given a new antibiotic called isoniazid, which caused some unexpected side effects. The patients reported euphoria, mental stimulation, and improved sleep, and even began socializing with more vigor. The press was all over the case, writing about the sick “dancing in the halls tho’ they had holes in their lungs.” Soon doctors started prescribing isoniazid as the first-ever antidepressant.

ChrisChrisW/iStock/Getty Images

The Sea View Hospital experiment was an early hint that changing the composition of the gut microbiome – in this case, via antibiotics – might affect our mental health. Yet only in the last 2 decades has research into connections between what we ingest and psychiatric disorders really taken off. In 2004, a landmark study showed that germ-free mice (born in such sterile conditions that they lacked a microbiome) had an exaggerated stress response. The effects were reversed, however, if the mice were fed a bacterial strain, Bifidobacterium infantis, a probiotic. This sparked academic interest, and thousands of research papers followed.

According to Stephen Ilardi, PhD, a clinical psychologist at the University of Kansas, Lawrence, focusing on the etiology and treatment of depression, now is the “time of exciting discovery” in the field of probiotics and psychiatric disorders, although, admittedly, a lot still remains unknown.
 

Gut microbiome profiles in mental health disorders

We humans have about 100 trillion microbes residing in our guts. Some of these are archaea, some fungi, some protozoans and even viruses, but most are bacteria. Things like diet, sleep, and stress can all impact the composition of our gut microbiome. When the microbiome differs considerably from the typical, doctors and researchers describe it as dysbiosis, or imbalance. Studies have uncovered dysbiosis in patients with depression, anxiety, schizophrenia, and bipolar disorder.

“I think there is now pretty good evidence that the gut microbiome is actually an important factor in a number of psychiatric disorders,” says Allan Young, MBChB, clinical psychiatrist at King’s College London. The gut microbiome composition does seem to differ between psychiatric patients and the healthy. In depression, for example, a recent review of nine studies found an increase on the genus level in Streptococcus and Oscillibacter and low abundance of Lactobacillus and Coprococcus, among others. In generalized anxiety disorder, meanwhile, there appears to be an increase in Fusobacteria and Escherichia/Shigella .

For Dr. Ilardi, the next important question is whether there are plausible mechanisms that could explain how gut microbiota may influence brain function. And, it appears there are.

“The microbes in the gut can release neurotransmitters into blood that cross into the brain and influence brain function. They can release hormones into the blood that again cross into the brain. They’ve got a lot of tricks up their sleeve,” he says.

One particularly important pathway runs through the vagus nerve – the longest nerve that emerges directly from the brain, connecting it to the gut. Another is the immune pathway. Gut bacteria can interact with immune cells and reduce cytokine production, which in turn can reduce systemic inflammation. Inflammatory processes have been implicated in both depression and bipolar disorder. What’s more, gut microbes can upregulate the expression of a protein called BDNF – brain-derived neurotrophic factor – which helps the development and survival of nerve cells in the brain.
 

Probiotics’ promise varies for different conditions

As the pathways by which gut dysbiosis may influence psychiatric disorders become clearer, the next logical step is to try to influence the composition of the microbiome to prevent and treat depression, anxiety, or schizophrenia. That’s where probiotics come in.

The evidence for the effects of probiotics – live microorganisms which, when ingested in adequate amounts, confer a health benefit – so far is the strongest for depression, says Viktoriya Nikolova, MRes, MSc, a PhD student and researcher at King’s College London. In their 2021 meta-analysis of seven trials, Mr. Nikolova and colleagues revealed that probiotics can significantly reduce depressive symptoms after just 8 weeks. There was a caveat, however – the probiotics only worked when used in addition to an approved antidepressant. Another meta-analysis, published in 2018, also showed that probiotics, when compared with placebo, improve mood in people with depressive symptoms (here, no antidepressant treatment was necessary).

Roumen Milev, MD, PhD, a neuroscientist at Queen’s University, Kingston, Ont., and coauthor of a review on probiotics and depression published in the Annals of General Psychiatry, warns, however, that the research is still in its infancy. “Currently, the probiotics should be used concomitant with antidepressant treatment,” he says.

When it comes to using probiotics to relieve anxiety, “the evidence in the animal literature is really compelling,” says Dr. Ilardi. Human studies are less convincing, however, which Dr. Dr. Ilardi showed in his 2018 review and meta-analysis involving 743 animals and 1,527 humans. “Studies are small for the most part, and some of them aren’t terribly well conducted, and they often use very low doses of probiotics,” he says. One of the larger double-blind and placebo-controlled trials showed that supplementation with Lactobacillus plantarum helps reduce stress and anxiety, while the levels of proinflammatory cytokines go down. Another meta-analysis, published in June, revealed that, when it comes to reducing stress and anxiety in youth, the results are mixed.

Evidence of probiotics’ efficiency in schizophrenia is emerging, yet also limited. A 2019 review concluded that currently available results only “hint” at a possibility that probiotics could make a difference in schizophrenia. Similarly, a 2020 review summed up that the role of probiotics in bipolar disorder “remains unclear and underexplored.”
 

Better studies, remaining questions

Apart from small samples, one issue with research on probiotics is that they generally tend to use varied doses of different strains of bacteria, or even multistrain mixtures, making it tough to compare results. Although there are hundreds of species of bacteria in the human gut, only a few have been evaluated for their antidepressant or antianxiety effects.

“To make it even worse, it’s almost certainly the case that depending on a person’s actual genetics or maybe their epigenetics, a strain that is helpful for one person may not be helpful for another. There is almost certainly no one-size-fits-all probiotic formulation,” says Dr. Ilardi.

Another critical question that remains to be answered is that of potential side effects.

“Probiotics are often seen as food supplements, so they don’t follow under the same regulations as drugs would,” says Mr. Nikolova. “They don’t necessarily have to follow the pattern of drug trials in many countries, which means that the monitoring of side effects is not the requirement.”

That’s something that worries King’s College psychiatrist Young too. “If you are giving it to modulate how the brain works, you could potentially induce psychiatric symptoms or a psychiatric disorder. There could be allergic reactions. There could be lots of different things,” he says.

When you search the web for “probiotics,” chances are you will come across sites boasting amazing effects that such products can have on cardiovascular heath, the immune system, and yes, mental well-being. Many also sell various probiotic supplements “formulated” for your gut health or improved moods. However, many such commercially available strains have never been actually tested in clinical trials. What’s more, according to Kathrin Cohen Kadosh, PhD, a neuroscientist at University of Surrey (England), “it is not always clear whether the different strains actually reach the gut intact.”

For now, considering the limited research evidence, a safer bet is to try to improve gut health through consumption of fermented foods that naturally contain probiotics, such as miso, kefir, or sauerkraut. Alternatively, you could reach for prebiotics, such as foods containing fiber (prebiotics enhance the growth of beneficial gut microbes). This, Dr. Kadosh says, could be “a gentler way of improving gut health” than popping a pill. Whether an improved mental well-being might follow still remains to be seen.

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

In 1950, at Staten Island’s Sea View Hospital, a group of patients with terminal tuberculosis were given a new antibiotic called isoniazid, which caused some unexpected side effects. The patients reported euphoria, mental stimulation, and improved sleep, and even began socializing with more vigor. The press was all over the case, writing about the sick “dancing in the halls tho’ they had holes in their lungs.” Soon doctors started prescribing isoniazid as the first-ever antidepressant.

ChrisChrisW/iStock/Getty Images

The Sea View Hospital experiment was an early hint that changing the composition of the gut microbiome – in this case, via antibiotics – might affect our mental health. Yet only in the last 2 decades has research into connections between what we ingest and psychiatric disorders really taken off. In 2004, a landmark study showed that germ-free mice (born in such sterile conditions that they lacked a microbiome) had an exaggerated stress response. The effects were reversed, however, if the mice were fed a bacterial strain, Bifidobacterium infantis, a probiotic. This sparked academic interest, and thousands of research papers followed.

According to Stephen Ilardi, PhD, a clinical psychologist at the University of Kansas, Lawrence, focusing on the etiology and treatment of depression, now is the “time of exciting discovery” in the field of probiotics and psychiatric disorders, although, admittedly, a lot still remains unknown.
 

Gut microbiome profiles in mental health disorders

We humans have about 100 trillion microbes residing in our guts. Some of these are archaea, some fungi, some protozoans and even viruses, but most are bacteria. Things like diet, sleep, and stress can all impact the composition of our gut microbiome. When the microbiome differs considerably from the typical, doctors and researchers describe it as dysbiosis, or imbalance. Studies have uncovered dysbiosis in patients with depression, anxiety, schizophrenia, and bipolar disorder.

“I think there is now pretty good evidence that the gut microbiome is actually an important factor in a number of psychiatric disorders,” says Allan Young, MBChB, clinical psychiatrist at King’s College London. The gut microbiome composition does seem to differ between psychiatric patients and the healthy. In depression, for example, a recent review of nine studies found an increase on the genus level in Streptococcus and Oscillibacter and low abundance of Lactobacillus and Coprococcus, among others. In generalized anxiety disorder, meanwhile, there appears to be an increase in Fusobacteria and Escherichia/Shigella .

For Dr. Ilardi, the next important question is whether there are plausible mechanisms that could explain how gut microbiota may influence brain function. And, it appears there are.

“The microbes in the gut can release neurotransmitters into blood that cross into the brain and influence brain function. They can release hormones into the blood that again cross into the brain. They’ve got a lot of tricks up their sleeve,” he says.

One particularly important pathway runs through the vagus nerve – the longest nerve that emerges directly from the brain, connecting it to the gut. Another is the immune pathway. Gut bacteria can interact with immune cells and reduce cytokine production, which in turn can reduce systemic inflammation. Inflammatory processes have been implicated in both depression and bipolar disorder. What’s more, gut microbes can upregulate the expression of a protein called BDNF – brain-derived neurotrophic factor – which helps the development and survival of nerve cells in the brain.
 

Probiotics’ promise varies for different conditions

As the pathways by which gut dysbiosis may influence psychiatric disorders become clearer, the next logical step is to try to influence the composition of the microbiome to prevent and treat depression, anxiety, or schizophrenia. That’s where probiotics come in.

The evidence for the effects of probiotics – live microorganisms which, when ingested in adequate amounts, confer a health benefit – so far is the strongest for depression, says Viktoriya Nikolova, MRes, MSc, a PhD student and researcher at King’s College London. In their 2021 meta-analysis of seven trials, Mr. Nikolova and colleagues revealed that probiotics can significantly reduce depressive symptoms after just 8 weeks. There was a caveat, however – the probiotics only worked when used in addition to an approved antidepressant. Another meta-analysis, published in 2018, also showed that probiotics, when compared with placebo, improve mood in people with depressive symptoms (here, no antidepressant treatment was necessary).

Roumen Milev, MD, PhD, a neuroscientist at Queen’s University, Kingston, Ont., and coauthor of a review on probiotics and depression published in the Annals of General Psychiatry, warns, however, that the research is still in its infancy. “Currently, the probiotics should be used concomitant with antidepressant treatment,” he says.

When it comes to using probiotics to relieve anxiety, “the evidence in the animal literature is really compelling,” says Dr. Ilardi. Human studies are less convincing, however, which Dr. Dr. Ilardi showed in his 2018 review and meta-analysis involving 743 animals and 1,527 humans. “Studies are small for the most part, and some of them aren’t terribly well conducted, and they often use very low doses of probiotics,” he says. One of the larger double-blind and placebo-controlled trials showed that supplementation with Lactobacillus plantarum helps reduce stress and anxiety, while the levels of proinflammatory cytokines go down. Another meta-analysis, published in June, revealed that, when it comes to reducing stress and anxiety in youth, the results are mixed.

Evidence of probiotics’ efficiency in schizophrenia is emerging, yet also limited. A 2019 review concluded that currently available results only “hint” at a possibility that probiotics could make a difference in schizophrenia. Similarly, a 2020 review summed up that the role of probiotics in bipolar disorder “remains unclear and underexplored.”
 

Better studies, remaining questions

Apart from small samples, one issue with research on probiotics is that they generally tend to use varied doses of different strains of bacteria, or even multistrain mixtures, making it tough to compare results. Although there are hundreds of species of bacteria in the human gut, only a few have been evaluated for their antidepressant or antianxiety effects.

“To make it even worse, it’s almost certainly the case that depending on a person’s actual genetics or maybe their epigenetics, a strain that is helpful for one person may not be helpful for another. There is almost certainly no one-size-fits-all probiotic formulation,” says Dr. Ilardi.

Another critical question that remains to be answered is that of potential side effects.

“Probiotics are often seen as food supplements, so they don’t follow under the same regulations as drugs would,” says Mr. Nikolova. “They don’t necessarily have to follow the pattern of drug trials in many countries, which means that the monitoring of side effects is not the requirement.”

That’s something that worries King’s College psychiatrist Young too. “If you are giving it to modulate how the brain works, you could potentially induce psychiatric symptoms or a psychiatric disorder. There could be allergic reactions. There could be lots of different things,” he says.

When you search the web for “probiotics,” chances are you will come across sites boasting amazing effects that such products can have on cardiovascular heath, the immune system, and yes, mental well-being. Many also sell various probiotic supplements “formulated” for your gut health or improved moods. However, many such commercially available strains have never been actually tested in clinical trials. What’s more, according to Kathrin Cohen Kadosh, PhD, a neuroscientist at University of Surrey (England), “it is not always clear whether the different strains actually reach the gut intact.”

For now, considering the limited research evidence, a safer bet is to try to improve gut health through consumption of fermented foods that naturally contain probiotics, such as miso, kefir, or sauerkraut. Alternatively, you could reach for prebiotics, such as foods containing fiber (prebiotics enhance the growth of beneficial gut microbes). This, Dr. Kadosh says, could be “a gentler way of improving gut health” than popping a pill. Whether an improved mental well-being might follow still remains to be seen.

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

Seeking novelty is central to adolescence; experimentation is how they explore their identity, exert independence, and establish deep and connected relationships outside of the family. Research over the past 2 decades has demonstrated the neurobiological changes that underpin this increase in sensation seeking. Most adolescents are very good at assessing risk but are willing to tolerate higher levels of risk than adults in the pursuit of novelty.¹ If their knowledge base is limited or inaccurate, as is often the case with drugs and alcohol, accepting higher risk becomes more dangerous. Adolescents are more likely to trust their peers than their parents, but their pediatricians still have authority and credibility.

While there is ample credible information online (from the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration’s excellent websites, which can be recommended to teens), marijuana and hallucinogens (LSD and psilocybin) bear special discussion here because of changing legality and their potential medical utility. There is an emerging impression of safety with both; however, policy changes and for-profit marketing may not reflect the actual scientific evidence. You have the opportunity and authority to complicate your patient’s thinking by discussing the evidence supporting their medical utility, and the emerging evidence that both types of drugs may pose special risks for their developing brains.

By June 2021, marijuana was legal for recreational use in 19 states; Washington, D.C.; and Guam, and for “medical use” in 36 states and four territories. Entrepreneurs and activists have made spectacular claims that marijuana is effective for the treatment of everything from insomnia to PTSD, but the reality is less impressive. Of course, marijuana remains a schedule I drug under the federal Controlled Substances Act (1970), which has made it difficult for researchers to perform randomized controlled studies concerning treatment or risks.

However, there are a growing number of randomized controlled trials with synthetic cannabinoids (dronabinol and nabilone) and a (legal) drug derived from cannabis (cannabidiol or CBD, as distinct from the other active ingredient, tetrahydrocannabinol). There is Food and Drug Administration approval for CBD for the treatment of epilepsy in Lennox-Gastaut or Dravet syndrome in patients aged 2 years or younger, and for the synthetic agents for the treatment of chemotherapy-related nausea and vomiting in cancer patients and for the treatment of weight loss and muscle wasting related to HIV/AIDS. That’s it. There is some evidence that these agents may be effective for the treatment of muscle spasticity in multiple sclerosis, chronic pain of many etiologies, Tourette syndrome, insomnia related to multiple sclerosis and chronic pain, and possibly PTSD. But there have been multiple studies that have failed to demonstrate efficacy (or have demonstrated exacerbation) for a host of other medical and psychiatric problems.

While the evidence for marijuana’s medicinal uses is modest, there is substantial evidence that its use in adolescence carries risks. It is an addictive substance and regular use is associated with sustained modest cognitive impairment (a loss of up to eight IQ points in the clinically dependent) and higher rates of anxiety and depressive disorders. As with other substances, use before the age of 18 substantially raises the risk (as much as sevenfold) of developing addiction than the same rate of use in adulthood. The rate of schizophrenia in adolescents with heavy marijuana use is between six and seven times greater than in the general population, whereas similar adult use does not have this association.^2,3 Studies in rats have demonstrated that use during adolescence delays and permanently changes the maturation of the prefrontal cortex, an area of the brain that is essential for complex decision-making, sustaining attention, abstract reasoning, and impulse control.⁴ While we do not fully understand the exact nature of these changes, there is good reason to believe that regular marijuana use in adolescence leads to disruption of critical brain development and cognitive or even psychotic consequences. It is worth noting that the potency of many commercially available marijuana products is much higher than those that were studied, raising the risk and uncertainty further.

Hallucinogens, or “psychedelics” (from Greek for “mind manifesting”) are a class that includes LSD and psilocybin (a chemical found in over 200 species of mushrooms). They precipitate visual and auditory “hallucinations,” a loss of sense of self, and a sense of awe that may be transcendent or frightening. While psilocybin was used by many indigenous cultures in religious ceremonies, LSD was synthesized by a chemist at Sandoz in 1938 and made widely available for study until it was classified as a schedule I drug by the 1970 Controlled Substances Act. They are not addictive. Early research demonstrated promise in the treatment of alcohol dependence and several psychiatric conditions (including other addictions and treatment-resistant depression). Research resumed in 2018, demonstrating promise in the treatment of depression related to terminal illness. Research has also concerned the nature of consciousness and spiritual experiences. Hallucinogens have become popular in certain fields (high tech) as a means of optimizing creativity and performance (“microdosing”). There is modest evidence that use in people with a family history of psychotic illness may precipitate sustained psychotic symptoms. Regular use may further increase the risk of persistent psychosis and adolescent users of multiple substances are at high risk for regular hallucinogen use. Adolescents may think that ketamine, phencyclidine , and 3,4-methylenedioxymethamphetamine are also in this category, although they are different and considerably more risky drugs. Overall, these agents show therapeutic promise, but unless your young patients are facing depression related to a terminal illness and until we learn more from studies, the potential risk to their developing brains outweighs any potential benefits.

Aware of this information, you are ready to ask your adolescent patients about their drug and alcohol use and knowledge. Using phrases like “when did you first try ...” can increase the likelihood that your patients will be forthright with you. Or start by asking about what their friends are trying and talking about. Be curious about any drug and alcohol use at home. Find out what they are curious about, whom they trust, and where they get their information. Then you can offer your information about the dramatic changes happening in their brains (just like the rest of their bodies) and the special risks of drug use during this window of brain development. Acknowledge that the risks of marijuana use in adults may very well be lower than the risks of regular alcohol use but remind them about how their brains are different than those of adults. Delaying use until they are 18 (or ideally in their mid-20s when most brain development is complete), can dramatically lower these risks. For adolescents with a family history of addiction, psychosis, or mood and anxiety disorders, discuss the additional risks that drugs may present to them. And for those adolescents who acknowledge very early (before 13) or heavy use, be curious with them about whether they might be trying to “feel better” and not just “feel good.” Screen them for depression, suicidality, and anxiety disorders. Those underlying problems are treatable, but their course will only worsen with drug and alcohol use. You are in a unique position to help your adolescent patients make wise and well-informed choices and to get them assistance if they need it.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Romer D. Dev Psychobiol. 2010 Apr;52(3):263-76.

2. Szczepanski SM and Knight TR. Neuron. 2014;83:1002-18.

3. Renard J et al. Front Psychiatry. 2018;9:281.

4. Shen H. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):7-11.

Seeking novelty is central to adolescence; experimentation is how they explore their identity, exert independence, and establish deep and connected relationships outside of the family. Research over the past 2 decades has demonstrated the neurobiological changes that underpin this increase in sensation seeking. Most adolescents are very good at assessing risk but are willing to tolerate higher levels of risk than adults in the pursuit of novelty.¹ If their knowledge base is limited or inaccurate, as is often the case with drugs and alcohol, accepting higher risk becomes more dangerous. Adolescents are more likely to trust their peers than their parents, but their pediatricians still have authority and credibility.

While there is ample credible information online (from the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration’s excellent websites, which can be recommended to teens), marijuana and hallucinogens (LSD and psilocybin) bear special discussion here because of changing legality and their potential medical utility. There is an emerging impression of safety with both; however, policy changes and for-profit marketing may not reflect the actual scientific evidence. You have the opportunity and authority to complicate your patient’s thinking by discussing the evidence supporting their medical utility, and the emerging evidence that both types of drugs may pose special risks for their developing brains.

By June 2021, marijuana was legal for recreational use in 19 states; Washington, D.C.; and Guam, and for “medical use” in 36 states and four territories. Entrepreneurs and activists have made spectacular claims that marijuana is effective for the treatment of everything from insomnia to PTSD, but the reality is less impressive. Of course, marijuana remains a schedule I drug under the federal Controlled Substances Act (1970), which has made it difficult for researchers to perform randomized controlled studies concerning treatment or risks.

However, there are a growing number of randomized controlled trials with synthetic cannabinoids (dronabinol and nabilone) and a (legal) drug derived from cannabis (cannabidiol or CBD, as distinct from the other active ingredient, tetrahydrocannabinol). There is Food and Drug Administration approval for CBD for the treatment of epilepsy in Lennox-Gastaut or Dravet syndrome in patients aged 2 years or younger, and for the synthetic agents for the treatment of chemotherapy-related nausea and vomiting in cancer patients and for the treatment of weight loss and muscle wasting related to HIV/AIDS. That’s it. There is some evidence that these agents may be effective for the treatment of muscle spasticity in multiple sclerosis, chronic pain of many etiologies, Tourette syndrome, insomnia related to multiple sclerosis and chronic pain, and possibly PTSD. But there have been multiple studies that have failed to demonstrate efficacy (or have demonstrated exacerbation) for a host of other medical and psychiatric problems.

While the evidence for marijuana’s medicinal uses is modest, there is substantial evidence that its use in adolescence carries risks. It is an addictive substance and regular use is associated with sustained modest cognitive impairment (a loss of up to eight IQ points in the clinically dependent) and higher rates of anxiety and depressive disorders. As with other substances, use before the age of 18 substantially raises the risk (as much as sevenfold) of developing addiction than the same rate of use in adulthood. The rate of schizophrenia in adolescents with heavy marijuana use is between six and seven times greater than in the general population, whereas similar adult use does not have this association.^2,3 Studies in rats have demonstrated that use during adolescence delays and permanently changes the maturation of the prefrontal cortex, an area of the brain that is essential for complex decision-making, sustaining attention, abstract reasoning, and impulse control.⁴ While we do not fully understand the exact nature of these changes, there is good reason to believe that regular marijuana use in adolescence leads to disruption of critical brain development and cognitive or even psychotic consequences. It is worth noting that the potency of many commercially available marijuana products is much higher than those that were studied, raising the risk and uncertainty further.

Hallucinogens, or “psychedelics” (from Greek for “mind manifesting”) are a class that includes LSD and psilocybin (a chemical found in over 200 species of mushrooms). They precipitate visual and auditory “hallucinations,” a loss of sense of self, and a sense of awe that may be transcendent or frightening. While psilocybin was used by many indigenous cultures in religious ceremonies, LSD was synthesized by a chemist at Sandoz in 1938 and made widely available for study until it was classified as a schedule I drug by the 1970 Controlled Substances Act. They are not addictive. Early research demonstrated promise in the treatment of alcohol dependence and several psychiatric conditions (including other addictions and treatment-resistant depression). Research resumed in 2018, demonstrating promise in the treatment of depression related to terminal illness. Research has also concerned the nature of consciousness and spiritual experiences. Hallucinogens have become popular in certain fields (high tech) as a means of optimizing creativity and performance (“microdosing”). There is modest evidence that use in people with a family history of psychotic illness may precipitate sustained psychotic symptoms. Regular use may further increase the risk of persistent psychosis and adolescent users of multiple substances are at high risk for regular hallucinogen use. Adolescents may think that ketamine, phencyclidine , and 3,4-methylenedioxymethamphetamine are also in this category, although they are different and considerably more risky drugs. Overall, these agents show therapeutic promise, but unless your young patients are facing depression related to a terminal illness and until we learn more from studies, the potential risk to their developing brains outweighs any potential benefits.

Aware of this information, you are ready to ask your adolescent patients about their drug and alcohol use and knowledge. Using phrases like “when did you first try ...” can increase the likelihood that your patients will be forthright with you. Or start by asking about what their friends are trying and talking about. Be curious about any drug and alcohol use at home. Find out what they are curious about, whom they trust, and where they get their information. Then you can offer your information about the dramatic changes happening in their brains (just like the rest of their bodies) and the special risks of drug use during this window of brain development. Acknowledge that the risks of marijuana use in adults may very well be lower than the risks of regular alcohol use but remind them about how their brains are different than those of adults. Delaying use until they are 18 (or ideally in their mid-20s when most brain development is complete), can dramatically lower these risks. For adolescents with a family history of addiction, psychosis, or mood and anxiety disorders, discuss the additional risks that drugs may present to them. And for those adolescents who acknowledge very early (before 13) or heavy use, be curious with them about whether they might be trying to “feel better” and not just “feel good.” Screen them for depression, suicidality, and anxiety disorders. Those underlying problems are treatable, but their course will only worsen with drug and alcohol use. You are in a unique position to help your adolescent patients make wise and well-informed choices and to get them assistance if they need it.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Romer D. Dev Psychobiol. 2010 Apr;52(3):263-76.

2. Szczepanski SM and Knight TR. Neuron. 2014;83:1002-18.

3. Renard J et al. Front Psychiatry. 2018;9:281.

4. Shen H. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):7-11.

Seeking novelty is central to adolescence; experimentation is how they explore their identity, exert independence, and establish deep and connected relationships outside of the family. Research over the past 2 decades has demonstrated the neurobiological changes that underpin this increase in sensation seeking. Most adolescents are very good at assessing risk but are willing to tolerate higher levels of risk than adults in the pursuit of novelty.¹ If their knowledge base is limited or inaccurate, as is often the case with drugs and alcohol, accepting higher risk becomes more dangerous. Adolescents are more likely to trust their peers than their parents, but their pediatricians still have authority and credibility.

While there is ample credible information online (from the National Institute on Drug Abuse and the Substance Abuse and Mental Health Services Administration’s excellent websites, which can be recommended to teens), marijuana and hallucinogens (LSD and psilocybin) bear special discussion here because of changing legality and their potential medical utility. There is an emerging impression of safety with both; however, policy changes and for-profit marketing may not reflect the actual scientific evidence. You have the opportunity and authority to complicate your patient’s thinking by discussing the evidence supporting their medical utility, and the emerging evidence that both types of drugs may pose special risks for their developing brains.

By June 2021, marijuana was legal for recreational use in 19 states; Washington, D.C.; and Guam, and for “medical use” in 36 states and four territories. Entrepreneurs and activists have made spectacular claims that marijuana is effective for the treatment of everything from insomnia to PTSD, but the reality is less impressive. Of course, marijuana remains a schedule I drug under the federal Controlled Substances Act (1970), which has made it difficult for researchers to perform randomized controlled studies concerning treatment or risks.

However, there are a growing number of randomized controlled trials with synthetic cannabinoids (dronabinol and nabilone) and a (legal) drug derived from cannabis (cannabidiol or CBD, as distinct from the other active ingredient, tetrahydrocannabinol). There is Food and Drug Administration approval for CBD for the treatment of epilepsy in Lennox-Gastaut or Dravet syndrome in patients aged 2 years or younger, and for the synthetic agents for the treatment of chemotherapy-related nausea and vomiting in cancer patients and for the treatment of weight loss and muscle wasting related to HIV/AIDS. That’s it. There is some evidence that these agents may be effective for the treatment of muscle spasticity in multiple sclerosis, chronic pain of many etiologies, Tourette syndrome, insomnia related to multiple sclerosis and chronic pain, and possibly PTSD. But there have been multiple studies that have failed to demonstrate efficacy (or have demonstrated exacerbation) for a host of other medical and psychiatric problems.

While the evidence for marijuana’s medicinal uses is modest, there is substantial evidence that its use in adolescence carries risks. It is an addictive substance and regular use is associated with sustained modest cognitive impairment (a loss of up to eight IQ points in the clinically dependent) and higher rates of anxiety and depressive disorders. As with other substances, use before the age of 18 substantially raises the risk (as much as sevenfold) of developing addiction than the same rate of use in adulthood. The rate of schizophrenia in adolescents with heavy marijuana use is between six and seven times greater than in the general population, whereas similar adult use does not have this association.^2,3 Studies in rats have demonstrated that use during adolescence delays and permanently changes the maturation of the prefrontal cortex, an area of the brain that is essential for complex decision-making, sustaining attention, abstract reasoning, and impulse control.⁴ While we do not fully understand the exact nature of these changes, there is good reason to believe that regular marijuana use in adolescence leads to disruption of critical brain development and cognitive or even psychotic consequences. It is worth noting that the potency of many commercially available marijuana products is much higher than those that were studied, raising the risk and uncertainty further.

Hallucinogens, or “psychedelics” (from Greek for “mind manifesting”) are a class that includes LSD and psilocybin (a chemical found in over 200 species of mushrooms). They precipitate visual and auditory “hallucinations,” a loss of sense of self, and a sense of awe that may be transcendent or frightening. While psilocybin was used by many indigenous cultures in religious ceremonies, LSD was synthesized by a chemist at Sandoz in 1938 and made widely available for study until it was classified as a schedule I drug by the 1970 Controlled Substances Act. They are not addictive. Early research demonstrated promise in the treatment of alcohol dependence and several psychiatric conditions (including other addictions and treatment-resistant depression). Research resumed in 2018, demonstrating promise in the treatment of depression related to terminal illness. Research has also concerned the nature of consciousness and spiritual experiences. Hallucinogens have become popular in certain fields (high tech) as a means of optimizing creativity and performance (“microdosing”). There is modest evidence that use in people with a family history of psychotic illness may precipitate sustained psychotic symptoms. Regular use may further increase the risk of persistent psychosis and adolescent users of multiple substances are at high risk for regular hallucinogen use. Adolescents may think that ketamine, phencyclidine , and 3,4-methylenedioxymethamphetamine are also in this category, although they are different and considerably more risky drugs. Overall, these agents show therapeutic promise, but unless your young patients are facing depression related to a terminal illness and until we learn more from studies, the potential risk to their developing brains outweighs any potential benefits.

Aware of this information, you are ready to ask your adolescent patients about their drug and alcohol use and knowledge. Using phrases like “when did you first try ...” can increase the likelihood that your patients will be forthright with you. Or start by asking about what their friends are trying and talking about. Be curious about any drug and alcohol use at home. Find out what they are curious about, whom they trust, and where they get their information. Then you can offer your information about the dramatic changes happening in their brains (just like the rest of their bodies) and the special risks of drug use during this window of brain development. Acknowledge that the risks of marijuana use in adults may very well be lower than the risks of regular alcohol use but remind them about how their brains are different than those of adults. Delaying use until they are 18 (or ideally in their mid-20s when most brain development is complete), can dramatically lower these risks. For adolescents with a family history of addiction, psychosis, or mood and anxiety disorders, discuss the additional risks that drugs may present to them. And for those adolescents who acknowledge very early (before 13) or heavy use, be curious with them about whether they might be trying to “feel better” and not just “feel good.” Screen them for depression, suicidality, and anxiety disorders. Those underlying problems are treatable, but their course will only worsen with drug and alcohol use. You are in a unique position to help your adolescent patients make wise and well-informed choices and to get them assistance if they need it.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Romer D. Dev Psychobiol. 2010 Apr;52(3):263-76.

2. Szczepanski SM and Knight TR. Neuron. 2014;83:1002-18.

3. Renard J et al. Front Psychiatry. 2018;9:281.

4. Shen H. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):7-11.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.