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Experts: EPA should assess risk of sunscreens’ UV filters
The , an expert panel of the National Academies of Sciences, Engineering, and Medicine (NAS) said on Aug. 9.
The assessment is urgently needed, the experts said, and the results should be shared with the Food and Drug Administration, which oversees sunscreens.
In its 400-page report, titled the Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health, the panel does not make recommendations but suggests that such an EPA risk assessment should highlight gaps in knowledge.
“We are teeing up the critical information that will be used to take on the challenge of risk assessment,” Charles A. Menzie, PhD, chair of the committee that wrote the report, said at a media briefing Aug. 9 when the report was released. Dr. Menzie is a principal at Exponent, Inc., an engineering and scientific consulting firm. He is former executive director of the Society of Environmental Toxicology and Chemistry.
The EPA sponsored the study, which was conducted by a committee of the National Academy of Sciences, a nonprofit, nongovernmental organization authorized by Congress that studies issues related to science, technology, and medicine.
Balancing aquatic, human health concerns
Such an EPA assessment, Dr. Menzie said in a statement, will help inform efforts to understand the environmental effects of UV filters as well as clarify a path forward for managing sunscreens. For years, concerns have been raised about the potential toxicity of sunscreens regarding many marine and freshwater aquatic organisms, especially coral. That concern, however, must be balanced against the benefits of sunscreens, which are known to protect against skin cancer. A low percentage of people use sunscreen regularly, Dr. Menzie and other panel members said.
“Only about a third of the U.S. population regularly uses sunscreen,” Mark Cullen, MD, vice chair of the NAS committee and former director of the Center for Population Health Sciences, Stanford (Calif.) University, said at the briefing. About 70% or 80% of people use it at the beach or outdoors, he said.
Report background, details
UV filters are the active ingredients in physical as well as chemical sunscreen products. They decrease the amount of UV radiation that reaches the skin. They have been found in water, sediments, and marine organisms, both saltwater and freshwater.
Currently, 17 UV filters are used in U.S. sunscreens; 15 of those are organic, such as oxybenzone and avobenzone, and are used in chemical sunscreens. They work by absorbing the rays before they damage the skin. In addition, two inorganic filters, which are used in physical sunscreens, sit on the skin and as a shield to block the rays.
UV filters enter bodies of water by direct release, as when sunscreens rinse off people while swimming or while engaging in other water activities. They also enter bodies of water in storm water runoff and wastewater.
Lab toxicity tests, which are the most widely used, provide effects data for ecologic risk assessment. The tests are more often used in the study of short-term, not long-term exposure. Test results have shown that in high enough concentrations, some UV filters can be toxic to algal, invertebrate, and fish species.
But much information is lacking, the experts said. Toxicity data for many species, for instance, are limited. There are few studies on the longer-term environmental effects of UV filter exposure. Not enough is known about the rate at which the filters degrade in the environment. The filters accumulate in higher amounts in different areas. Recreational water areas have higher concentrations.
The recommendations
The panel is urging the EPA to complete a formal risk assessment of the UV filters “with some urgency,” Dr. Cullen said. That will enable decisions to be made about the use of the products. The risks to aquatic life must be balanced against the need for sun protection to reduce skin cancer risk.
The experts made two recommendations:
- The EPA should conduct ecologic risk assessments for all the UV filters now marketed and for all new ones. The assessment should evaluate the filters individually as well as the risk from co-occurring filters. The assessments should take into account the different exposure scenarios.
- The EPA, along with partner agencies, and sunscreen and UV filter manufacturers should fund, support, and conduct research and share data. Research should include study of human health outcomes if usage and availability of sunscreens change.
Dermatologists should “continue to emphasize the importance of protection from UV radiation in every way that can be done,” Dr. Cullen said, including the use of sunscreen as well as other protective practices, such as wearing long sleeves and hats, seeking shade, and avoiding the sun during peak hours.
A dermatologist’s perspective
“I applaud their scientific curiosity to know one way or the other whether this is an issue,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC. “I welcome this investigation.”
The multitude of studies, Dr. Friedman said, don’t always agree about whether the filters pose dangers. He noted that the concentration of UV filters detected in water is often lower than the concentrations found to be harmful in a lab setting to marine life, specifically coral.
However, he said, “these studies are snapshots.” For that reason, calling for more assessment of risk is desirable, Dr. Friedman said, but “I want to be sure the call to do more research is not an admission of guilt. It’s very easy to vilify sunscreens – but the facts we know are that UV light causes skin cancer and aging, and sunscreen protects us against this.”
Dr. Friedman has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The , an expert panel of the National Academies of Sciences, Engineering, and Medicine (NAS) said on Aug. 9.
The assessment is urgently needed, the experts said, and the results should be shared with the Food and Drug Administration, which oversees sunscreens.
In its 400-page report, titled the Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health, the panel does not make recommendations but suggests that such an EPA risk assessment should highlight gaps in knowledge.
“We are teeing up the critical information that will be used to take on the challenge of risk assessment,” Charles A. Menzie, PhD, chair of the committee that wrote the report, said at a media briefing Aug. 9 when the report was released. Dr. Menzie is a principal at Exponent, Inc., an engineering and scientific consulting firm. He is former executive director of the Society of Environmental Toxicology and Chemistry.
The EPA sponsored the study, which was conducted by a committee of the National Academy of Sciences, a nonprofit, nongovernmental organization authorized by Congress that studies issues related to science, technology, and medicine.
Balancing aquatic, human health concerns
Such an EPA assessment, Dr. Menzie said in a statement, will help inform efforts to understand the environmental effects of UV filters as well as clarify a path forward for managing sunscreens. For years, concerns have been raised about the potential toxicity of sunscreens regarding many marine and freshwater aquatic organisms, especially coral. That concern, however, must be balanced against the benefits of sunscreens, which are known to protect against skin cancer. A low percentage of people use sunscreen regularly, Dr. Menzie and other panel members said.
“Only about a third of the U.S. population regularly uses sunscreen,” Mark Cullen, MD, vice chair of the NAS committee and former director of the Center for Population Health Sciences, Stanford (Calif.) University, said at the briefing. About 70% or 80% of people use it at the beach or outdoors, he said.
Report background, details
UV filters are the active ingredients in physical as well as chemical sunscreen products. They decrease the amount of UV radiation that reaches the skin. They have been found in water, sediments, and marine organisms, both saltwater and freshwater.
Currently, 17 UV filters are used in U.S. sunscreens; 15 of those are organic, such as oxybenzone and avobenzone, and are used in chemical sunscreens. They work by absorbing the rays before they damage the skin. In addition, two inorganic filters, which are used in physical sunscreens, sit on the skin and as a shield to block the rays.
UV filters enter bodies of water by direct release, as when sunscreens rinse off people while swimming or while engaging in other water activities. They also enter bodies of water in storm water runoff and wastewater.
Lab toxicity tests, which are the most widely used, provide effects data for ecologic risk assessment. The tests are more often used in the study of short-term, not long-term exposure. Test results have shown that in high enough concentrations, some UV filters can be toxic to algal, invertebrate, and fish species.
But much information is lacking, the experts said. Toxicity data for many species, for instance, are limited. There are few studies on the longer-term environmental effects of UV filter exposure. Not enough is known about the rate at which the filters degrade in the environment. The filters accumulate in higher amounts in different areas. Recreational water areas have higher concentrations.
The recommendations
The panel is urging the EPA to complete a formal risk assessment of the UV filters “with some urgency,” Dr. Cullen said. That will enable decisions to be made about the use of the products. The risks to aquatic life must be balanced against the need for sun protection to reduce skin cancer risk.
The experts made two recommendations:
- The EPA should conduct ecologic risk assessments for all the UV filters now marketed and for all new ones. The assessment should evaluate the filters individually as well as the risk from co-occurring filters. The assessments should take into account the different exposure scenarios.
- The EPA, along with partner agencies, and sunscreen and UV filter manufacturers should fund, support, and conduct research and share data. Research should include study of human health outcomes if usage and availability of sunscreens change.
Dermatologists should “continue to emphasize the importance of protection from UV radiation in every way that can be done,” Dr. Cullen said, including the use of sunscreen as well as other protective practices, such as wearing long sleeves and hats, seeking shade, and avoiding the sun during peak hours.
A dermatologist’s perspective
“I applaud their scientific curiosity to know one way or the other whether this is an issue,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC. “I welcome this investigation.”
The multitude of studies, Dr. Friedman said, don’t always agree about whether the filters pose dangers. He noted that the concentration of UV filters detected in water is often lower than the concentrations found to be harmful in a lab setting to marine life, specifically coral.
However, he said, “these studies are snapshots.” For that reason, calling for more assessment of risk is desirable, Dr. Friedman said, but “I want to be sure the call to do more research is not an admission of guilt. It’s very easy to vilify sunscreens – but the facts we know are that UV light causes skin cancer and aging, and sunscreen protects us against this.”
Dr. Friedman has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The , an expert panel of the National Academies of Sciences, Engineering, and Medicine (NAS) said on Aug. 9.
The assessment is urgently needed, the experts said, and the results should be shared with the Food and Drug Administration, which oversees sunscreens.
In its 400-page report, titled the Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health, the panel does not make recommendations but suggests that such an EPA risk assessment should highlight gaps in knowledge.
“We are teeing up the critical information that will be used to take on the challenge of risk assessment,” Charles A. Menzie, PhD, chair of the committee that wrote the report, said at a media briefing Aug. 9 when the report was released. Dr. Menzie is a principal at Exponent, Inc., an engineering and scientific consulting firm. He is former executive director of the Society of Environmental Toxicology and Chemistry.
The EPA sponsored the study, which was conducted by a committee of the National Academy of Sciences, a nonprofit, nongovernmental organization authorized by Congress that studies issues related to science, technology, and medicine.
Balancing aquatic, human health concerns
Such an EPA assessment, Dr. Menzie said in a statement, will help inform efforts to understand the environmental effects of UV filters as well as clarify a path forward for managing sunscreens. For years, concerns have been raised about the potential toxicity of sunscreens regarding many marine and freshwater aquatic organisms, especially coral. That concern, however, must be balanced against the benefits of sunscreens, which are known to protect against skin cancer. A low percentage of people use sunscreen regularly, Dr. Menzie and other panel members said.
“Only about a third of the U.S. population regularly uses sunscreen,” Mark Cullen, MD, vice chair of the NAS committee and former director of the Center for Population Health Sciences, Stanford (Calif.) University, said at the briefing. About 70% or 80% of people use it at the beach or outdoors, he said.
Report background, details
UV filters are the active ingredients in physical as well as chemical sunscreen products. They decrease the amount of UV radiation that reaches the skin. They have been found in water, sediments, and marine organisms, both saltwater and freshwater.
Currently, 17 UV filters are used in U.S. sunscreens; 15 of those are organic, such as oxybenzone and avobenzone, and are used in chemical sunscreens. They work by absorbing the rays before they damage the skin. In addition, two inorganic filters, which are used in physical sunscreens, sit on the skin and as a shield to block the rays.
UV filters enter bodies of water by direct release, as when sunscreens rinse off people while swimming or while engaging in other water activities. They also enter bodies of water in storm water runoff and wastewater.
Lab toxicity tests, which are the most widely used, provide effects data for ecologic risk assessment. The tests are more often used in the study of short-term, not long-term exposure. Test results have shown that in high enough concentrations, some UV filters can be toxic to algal, invertebrate, and fish species.
But much information is lacking, the experts said. Toxicity data for many species, for instance, are limited. There are few studies on the longer-term environmental effects of UV filter exposure. Not enough is known about the rate at which the filters degrade in the environment. The filters accumulate in higher amounts in different areas. Recreational water areas have higher concentrations.
The recommendations
The panel is urging the EPA to complete a formal risk assessment of the UV filters “with some urgency,” Dr. Cullen said. That will enable decisions to be made about the use of the products. The risks to aquatic life must be balanced against the need for sun protection to reduce skin cancer risk.
The experts made two recommendations:
- The EPA should conduct ecologic risk assessments for all the UV filters now marketed and for all new ones. The assessment should evaluate the filters individually as well as the risk from co-occurring filters. The assessments should take into account the different exposure scenarios.
- The EPA, along with partner agencies, and sunscreen and UV filter manufacturers should fund, support, and conduct research and share data. Research should include study of human health outcomes if usage and availability of sunscreens change.
Dermatologists should “continue to emphasize the importance of protection from UV radiation in every way that can be done,” Dr. Cullen said, including the use of sunscreen as well as other protective practices, such as wearing long sleeves and hats, seeking shade, and avoiding the sun during peak hours.
A dermatologist’s perspective
“I applaud their scientific curiosity to know one way or the other whether this is an issue,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC. “I welcome this investigation.”
The multitude of studies, Dr. Friedman said, don’t always agree about whether the filters pose dangers. He noted that the concentration of UV filters detected in water is often lower than the concentrations found to be harmful in a lab setting to marine life, specifically coral.
However, he said, “these studies are snapshots.” For that reason, calling for more assessment of risk is desirable, Dr. Friedman said, but “I want to be sure the call to do more research is not an admission of guilt. It’s very easy to vilify sunscreens – but the facts we know are that UV light causes skin cancer and aging, and sunscreen protects us against this.”
Dr. Friedman has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Weight-loss surgery has a big effect on marriage
Kristal was only in her mid-30s when she decided to have surgery. Her doctor said it was too early. But the Oregon mom of three had found herself in the hospital twice for obesity-related lung complications before her 35th birthday. So she got the gastric sleeve.
And at first it seemed like the best decision for her and her family. She was losing weight – 100 pounds in 16 months – and so was her husband. The whole family was more active and seemed to have more energy. But then her husband’s weight began to creep back up.
While she joined a running group and signed up for half-marathons, her husband’s depression and drinking worsened. The healthier lifestyle they’d shared was now an unspoken wedge between them.
And the added attention Kristal was getting from men and women because of her thinner size only added to the tension. After 30 years together and 22 years of marriage, the high school sweethearts divorced in June 2021. Kristal’s weight loss wasn’t the only problem, but she and her ex-husband believe it was the beginning of the end.
An unexpected outcome?
New research from the University of Pittsburgh found that Kristal’s experience is a common one. The study looked at data from 1,441 bariatric surgery patients and found that never-married patients were over 50% more likely to get married, and married patients were more than twice as likely to get divorced, compared to the general U.S. population.
This U.S. data follows two Scandinavian studies from 2018 and 2020 that found similar relationship changes after bariatric surgery. But the postsurgery divorce rate in the United States was only about half that found in the Danish and Swedish studies, according to the new study published in Annals of Surgery.
It’s important to note that even with an increase in the divorce rate, most marriages in the study were unchanged, said epidemiologist and lead author Wendy King, PhD. In fact, 81% of couples were still married 5 years after surgery. But where the U.S. population has a divorce rate of 3.5%, bariatric patients in the study had an 8% divorce rate. Likewise, those who’d never been married before the surgery had a marriage rate of 18%, compared to 7% in the U.S. population.
Surgery certainly isn’t a death sentence for a patient’s love life. But the uptick in marriage and divorce suggests bariatric surgery significantly impacts how people engage in relationships.
“It makes sense,” said clinical psychologist Rachel Goldman, PhD, who specializes in health and wellness issues and bariatric surgery cases in New York City. “People are changing their lifestyle.” And those changes don’t start or stop the day of surgery, they begin as soon as someone decides to have surgery and continue as a lifelong process, she said.
For some patients, these healthy habits may offer a “new lease on life,” said Dr. King. According to the study, patients who had better physical health after surgery were more likely to get married.
But the continual lifestyle changes can dramatically impact the rituals of existing relationships, said Dr. Goldman. Maybe a couple loved to go out and enjoy an extravagant meal before surgery, or they had ice cream and watched a movie every Friday. The habit changes that come with bariatric surgery can require one partner to focus less on those rituals.
These sorts of changes may leave one or both people feeling like their partner is turning away from them, said Don Cole, DMin, a relationship therapist and clinical director at the Gottman Institute in Seattle, a think tank focused on the science of relationships. The person who had surgery may feel unsupported in the new journey if the partner keeps advocating for unhealthy habits, he said. And the person who didn’t have surgery may feel cast aside by the partner’s new health priorities.
Changes, even those that are positive and healthy, create a kind of crisis for relationships, Dr. Cole said. It’s not just bariatric surgery. Bringing a baby into the home, infertility treatments, and substance abuse recovery are all considered positive changes that are also predictors of relationship dissatisfaction and divorce, he said.
A couple could have a range of emotions after one partner gets bariatric surgery, Dr. Cole said. Unfortunately, “my experience as a therapist says they aren’t that good [at talking about it],” he said.
But bariatric surgery isn’t the only thing at play in these relationship changes, according to the study. Married patients had a much lower chance of separation or divorce (13%) than patients who were unmarried but living together (44%) by 5 years after surgery. Similarly, most people who were already separated either got divorced or resumed being married. It’s as if the surgery and lifestyle changes served as a catalyst for people who already had one foot out of (or in) the door, Dr. Goldman said.
A high sexual desire after surgery was also a predictor of divorce. In fact, there were more things before surgery that impacted divorce than surgery-related changes. It’s possible that many of these patients are “on the path toward change already,” Dr. King said. “Who knows how much the surgery had to do with it.”
Dr. Goldman recalled a patient who, before surgery, had very low self-worth. She wasn’t satisfied with her relationship but admitted to staying because she didn’t believe she could do any better than her current partner. After surgery, her perspective radically changed. She started to get healthier, invested in her education, and changed jobs. And when her partner refused to join her in making changes, she left. Maybe some of these patients “were already thinking about leaving but just didn’t have the confidence,” Dr. Goldman said.
Still, it’s critical that patients receive more counseling on how choosing to have bariatric surgery can impact their relationship before and after their weight loss procedure, Dr. King said. It should be the standard of care.
Currently, relationship-specific counseling isn’t required, Dr. Goldman said. Most programs do require a psychosocial evaluation before surgery, “but they are quite varied.” And even in programs where relationships are mentioned, there often isn’t a psychologist or licensed mental health professional on the team.
Since Dr. King’s previous research on substance abuse after bariatric surgery changed common practice in the field, Dr. Goldman said she hopes the new data will have a similar influence and relationship counseling will become the norm.
Dr. Cole actually had bariatric surgery. He recalled potential relationship issues were briefly mentioned. Someone at the clinic said if his marriage felt challenged, he should seek help from a professional, and that was it.
For Dr. Cole, there were unexpected negative feelings of shame and disappointment after surgery. He felt the extreme weight loss was all his colleagues could talk about and was very disappointed when there was no change in his chronic pain, a primary reason he had the procedure.
Fortunately, he could talk to his wife – also is a relationship therapist at Gottman – about the range of emotions. “One of the things that we know that creates a deep sense of trust is [when] I know my partner is there for me when I’m not well,” Dr. Cole said.
But these negative emotions can be the very things that feel most difficult to talk about or hear from a partner. It’s hard to share our own negative feelings and to hear someone else’s, Dr. Cole said.
He advises creating a new “ritual of connection: moments in time when you plan to turn toward one another.”
That could be a daily walk, where you intentionally talk about the surgery-related changes that both of you have had. Dr. Cole said to ask yourself, “Are we intentional about turning toward one another in those [challenging] moments?”
A version of this article first appeared on WebMD.com.
Kristal was only in her mid-30s when she decided to have surgery. Her doctor said it was too early. But the Oregon mom of three had found herself in the hospital twice for obesity-related lung complications before her 35th birthday. So she got the gastric sleeve.
And at first it seemed like the best decision for her and her family. She was losing weight – 100 pounds in 16 months – and so was her husband. The whole family was more active and seemed to have more energy. But then her husband’s weight began to creep back up.
While she joined a running group and signed up for half-marathons, her husband’s depression and drinking worsened. The healthier lifestyle they’d shared was now an unspoken wedge between them.
And the added attention Kristal was getting from men and women because of her thinner size only added to the tension. After 30 years together and 22 years of marriage, the high school sweethearts divorced in June 2021. Kristal’s weight loss wasn’t the only problem, but she and her ex-husband believe it was the beginning of the end.
An unexpected outcome?
New research from the University of Pittsburgh found that Kristal’s experience is a common one. The study looked at data from 1,441 bariatric surgery patients and found that never-married patients were over 50% more likely to get married, and married patients were more than twice as likely to get divorced, compared to the general U.S. population.
This U.S. data follows two Scandinavian studies from 2018 and 2020 that found similar relationship changes after bariatric surgery. But the postsurgery divorce rate in the United States was only about half that found in the Danish and Swedish studies, according to the new study published in Annals of Surgery.
It’s important to note that even with an increase in the divorce rate, most marriages in the study were unchanged, said epidemiologist and lead author Wendy King, PhD. In fact, 81% of couples were still married 5 years after surgery. But where the U.S. population has a divorce rate of 3.5%, bariatric patients in the study had an 8% divorce rate. Likewise, those who’d never been married before the surgery had a marriage rate of 18%, compared to 7% in the U.S. population.
Surgery certainly isn’t a death sentence for a patient’s love life. But the uptick in marriage and divorce suggests bariatric surgery significantly impacts how people engage in relationships.
“It makes sense,” said clinical psychologist Rachel Goldman, PhD, who specializes in health and wellness issues and bariatric surgery cases in New York City. “People are changing their lifestyle.” And those changes don’t start or stop the day of surgery, they begin as soon as someone decides to have surgery and continue as a lifelong process, she said.
For some patients, these healthy habits may offer a “new lease on life,” said Dr. King. According to the study, patients who had better physical health after surgery were more likely to get married.
But the continual lifestyle changes can dramatically impact the rituals of existing relationships, said Dr. Goldman. Maybe a couple loved to go out and enjoy an extravagant meal before surgery, or they had ice cream and watched a movie every Friday. The habit changes that come with bariatric surgery can require one partner to focus less on those rituals.
These sorts of changes may leave one or both people feeling like their partner is turning away from them, said Don Cole, DMin, a relationship therapist and clinical director at the Gottman Institute in Seattle, a think tank focused on the science of relationships. The person who had surgery may feel unsupported in the new journey if the partner keeps advocating for unhealthy habits, he said. And the person who didn’t have surgery may feel cast aside by the partner’s new health priorities.
Changes, even those that are positive and healthy, create a kind of crisis for relationships, Dr. Cole said. It’s not just bariatric surgery. Bringing a baby into the home, infertility treatments, and substance abuse recovery are all considered positive changes that are also predictors of relationship dissatisfaction and divorce, he said.
A couple could have a range of emotions after one partner gets bariatric surgery, Dr. Cole said. Unfortunately, “my experience as a therapist says they aren’t that good [at talking about it],” he said.
But bariatric surgery isn’t the only thing at play in these relationship changes, according to the study. Married patients had a much lower chance of separation or divorce (13%) than patients who were unmarried but living together (44%) by 5 years after surgery. Similarly, most people who were already separated either got divorced or resumed being married. It’s as if the surgery and lifestyle changes served as a catalyst for people who already had one foot out of (or in) the door, Dr. Goldman said.
A high sexual desire after surgery was also a predictor of divorce. In fact, there were more things before surgery that impacted divorce than surgery-related changes. It’s possible that many of these patients are “on the path toward change already,” Dr. King said. “Who knows how much the surgery had to do with it.”
Dr. Goldman recalled a patient who, before surgery, had very low self-worth. She wasn’t satisfied with her relationship but admitted to staying because she didn’t believe she could do any better than her current partner. After surgery, her perspective radically changed. She started to get healthier, invested in her education, and changed jobs. And when her partner refused to join her in making changes, she left. Maybe some of these patients “were already thinking about leaving but just didn’t have the confidence,” Dr. Goldman said.
Still, it’s critical that patients receive more counseling on how choosing to have bariatric surgery can impact their relationship before and after their weight loss procedure, Dr. King said. It should be the standard of care.
Currently, relationship-specific counseling isn’t required, Dr. Goldman said. Most programs do require a psychosocial evaluation before surgery, “but they are quite varied.” And even in programs where relationships are mentioned, there often isn’t a psychologist or licensed mental health professional on the team.
Since Dr. King’s previous research on substance abuse after bariatric surgery changed common practice in the field, Dr. Goldman said she hopes the new data will have a similar influence and relationship counseling will become the norm.
Dr. Cole actually had bariatric surgery. He recalled potential relationship issues were briefly mentioned. Someone at the clinic said if his marriage felt challenged, he should seek help from a professional, and that was it.
For Dr. Cole, there were unexpected negative feelings of shame and disappointment after surgery. He felt the extreme weight loss was all his colleagues could talk about and was very disappointed when there was no change in his chronic pain, a primary reason he had the procedure.
Fortunately, he could talk to his wife – also is a relationship therapist at Gottman – about the range of emotions. “One of the things that we know that creates a deep sense of trust is [when] I know my partner is there for me when I’m not well,” Dr. Cole said.
But these negative emotions can be the very things that feel most difficult to talk about or hear from a partner. It’s hard to share our own negative feelings and to hear someone else’s, Dr. Cole said.
He advises creating a new “ritual of connection: moments in time when you plan to turn toward one another.”
That could be a daily walk, where you intentionally talk about the surgery-related changes that both of you have had. Dr. Cole said to ask yourself, “Are we intentional about turning toward one another in those [challenging] moments?”
A version of this article first appeared on WebMD.com.
Kristal was only in her mid-30s when she decided to have surgery. Her doctor said it was too early. But the Oregon mom of three had found herself in the hospital twice for obesity-related lung complications before her 35th birthday. So she got the gastric sleeve.
And at first it seemed like the best decision for her and her family. She was losing weight – 100 pounds in 16 months – and so was her husband. The whole family was more active and seemed to have more energy. But then her husband’s weight began to creep back up.
While she joined a running group and signed up for half-marathons, her husband’s depression and drinking worsened. The healthier lifestyle they’d shared was now an unspoken wedge between them.
And the added attention Kristal was getting from men and women because of her thinner size only added to the tension. After 30 years together and 22 years of marriage, the high school sweethearts divorced in June 2021. Kristal’s weight loss wasn’t the only problem, but she and her ex-husband believe it was the beginning of the end.
An unexpected outcome?
New research from the University of Pittsburgh found that Kristal’s experience is a common one. The study looked at data from 1,441 bariatric surgery patients and found that never-married patients were over 50% more likely to get married, and married patients were more than twice as likely to get divorced, compared to the general U.S. population.
This U.S. data follows two Scandinavian studies from 2018 and 2020 that found similar relationship changes after bariatric surgery. But the postsurgery divorce rate in the United States was only about half that found in the Danish and Swedish studies, according to the new study published in Annals of Surgery.
It’s important to note that even with an increase in the divorce rate, most marriages in the study were unchanged, said epidemiologist and lead author Wendy King, PhD. In fact, 81% of couples were still married 5 years after surgery. But where the U.S. population has a divorce rate of 3.5%, bariatric patients in the study had an 8% divorce rate. Likewise, those who’d never been married before the surgery had a marriage rate of 18%, compared to 7% in the U.S. population.
Surgery certainly isn’t a death sentence for a patient’s love life. But the uptick in marriage and divorce suggests bariatric surgery significantly impacts how people engage in relationships.
“It makes sense,” said clinical psychologist Rachel Goldman, PhD, who specializes in health and wellness issues and bariatric surgery cases in New York City. “People are changing their lifestyle.” And those changes don’t start or stop the day of surgery, they begin as soon as someone decides to have surgery and continue as a lifelong process, she said.
For some patients, these healthy habits may offer a “new lease on life,” said Dr. King. According to the study, patients who had better physical health after surgery were more likely to get married.
But the continual lifestyle changes can dramatically impact the rituals of existing relationships, said Dr. Goldman. Maybe a couple loved to go out and enjoy an extravagant meal before surgery, or they had ice cream and watched a movie every Friday. The habit changes that come with bariatric surgery can require one partner to focus less on those rituals.
These sorts of changes may leave one or both people feeling like their partner is turning away from them, said Don Cole, DMin, a relationship therapist and clinical director at the Gottman Institute in Seattle, a think tank focused on the science of relationships. The person who had surgery may feel unsupported in the new journey if the partner keeps advocating for unhealthy habits, he said. And the person who didn’t have surgery may feel cast aside by the partner’s new health priorities.
Changes, even those that are positive and healthy, create a kind of crisis for relationships, Dr. Cole said. It’s not just bariatric surgery. Bringing a baby into the home, infertility treatments, and substance abuse recovery are all considered positive changes that are also predictors of relationship dissatisfaction and divorce, he said.
A couple could have a range of emotions after one partner gets bariatric surgery, Dr. Cole said. Unfortunately, “my experience as a therapist says they aren’t that good [at talking about it],” he said.
But bariatric surgery isn’t the only thing at play in these relationship changes, according to the study. Married patients had a much lower chance of separation or divorce (13%) than patients who were unmarried but living together (44%) by 5 years after surgery. Similarly, most people who were already separated either got divorced or resumed being married. It’s as if the surgery and lifestyle changes served as a catalyst for people who already had one foot out of (or in) the door, Dr. Goldman said.
A high sexual desire after surgery was also a predictor of divorce. In fact, there were more things before surgery that impacted divorce than surgery-related changes. It’s possible that many of these patients are “on the path toward change already,” Dr. King said. “Who knows how much the surgery had to do with it.”
Dr. Goldman recalled a patient who, before surgery, had very low self-worth. She wasn’t satisfied with her relationship but admitted to staying because she didn’t believe she could do any better than her current partner. After surgery, her perspective radically changed. She started to get healthier, invested in her education, and changed jobs. And when her partner refused to join her in making changes, she left. Maybe some of these patients “were already thinking about leaving but just didn’t have the confidence,” Dr. Goldman said.
Still, it’s critical that patients receive more counseling on how choosing to have bariatric surgery can impact their relationship before and after their weight loss procedure, Dr. King said. It should be the standard of care.
Currently, relationship-specific counseling isn’t required, Dr. Goldman said. Most programs do require a psychosocial evaluation before surgery, “but they are quite varied.” And even in programs where relationships are mentioned, there often isn’t a psychologist or licensed mental health professional on the team.
Since Dr. King’s previous research on substance abuse after bariatric surgery changed common practice in the field, Dr. Goldman said she hopes the new data will have a similar influence and relationship counseling will become the norm.
Dr. Cole actually had bariatric surgery. He recalled potential relationship issues were briefly mentioned. Someone at the clinic said if his marriage felt challenged, he should seek help from a professional, and that was it.
For Dr. Cole, there were unexpected negative feelings of shame and disappointment after surgery. He felt the extreme weight loss was all his colleagues could talk about and was very disappointed when there was no change in his chronic pain, a primary reason he had the procedure.
Fortunately, he could talk to his wife – also is a relationship therapist at Gottman – about the range of emotions. “One of the things that we know that creates a deep sense of trust is [when] I know my partner is there for me when I’m not well,” Dr. Cole said.
But these negative emotions can be the very things that feel most difficult to talk about or hear from a partner. It’s hard to share our own negative feelings and to hear someone else’s, Dr. Cole said.
He advises creating a new “ritual of connection: moments in time when you plan to turn toward one another.”
That could be a daily walk, where you intentionally talk about the surgery-related changes that both of you have had. Dr. Cole said to ask yourself, “Are we intentional about turning toward one another in those [challenging] moments?”
A version of this article first appeared on WebMD.com.
FROM ANNALS OF SURGERY
Federal Health Care Data Trends 2022
Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.
In this issue:
- Vaccinations
- Mental Health and Related Disorders
- LGBTQ+ Veterans
- Military Sexual Trauma
- Sleep Disorders
- Respiratory Illnesses
- HIV Care in the VA
- Rheumatologic Diseases
- The Cancer-Obesity Connection
- Skin Health for Active-Duty Personnel
- Contraception
- Chronic Kidney Disease
- Cardiovascular Diseases
- Neurologic Disorders
- Hearing, Vision, and Balance
Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue:
Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN
Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.
In this issue:
- Vaccinations
- Mental Health and Related Disorders
- LGBTQ+ Veterans
- Military Sexual Trauma
- Sleep Disorders
- Respiratory Illnesses
- HIV Care in the VA
- Rheumatologic Diseases
- The Cancer-Obesity Connection
- Skin Health for Active-Duty Personnel
- Contraception
- Chronic Kidney Disease
- Cardiovascular Diseases
- Neurologic Disorders
- Hearing, Vision, and Balance
Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue:
Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN
Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.
In this issue:
- Vaccinations
- Mental Health and Related Disorders
- LGBTQ+ Veterans
- Military Sexual Trauma
- Sleep Disorders
- Respiratory Illnesses
- HIV Care in the VA
- Rheumatologic Diseases
- The Cancer-Obesity Connection
- Skin Health for Active-Duty Personnel
- Contraception
- Chronic Kidney Disease
- Cardiovascular Diseases
- Neurologic Disorders
- Hearing, Vision, and Balance
Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue:
Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN
Does hidradenitis suppurativa worsen during pregnancy?
PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.
In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.
“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.
“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.
During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.
She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.
“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”
To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.
“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”
Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.
As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.
Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.
“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.
Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.
“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”
As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.
“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”
Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.
“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”
To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.
Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.
“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”
Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”
In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.
“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).
Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”
In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.
HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.
After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.
A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”
Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.
PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.
In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.
“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.
“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.
During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.
She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.
“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”
To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.
“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”
Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.
As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.
Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.
“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.
Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.
“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”
As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.
“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”
Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.
“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”
To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.
Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.
“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”
Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”
In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.
“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).
Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”
In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.
HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.
After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.
A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”
Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.
PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.
In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.
“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.
“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.
During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.
She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.
“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”
To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.
“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”
Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.
As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.
Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.
“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.
Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.
“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”
As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.
“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”
Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.
“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”
To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.
Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.
“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”
Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”
In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.
“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).
Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”
In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.
HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.
After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.
A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”
Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.
AT PDA 2022
Stressed about weight gain? Well, stress causes weight gain
Stress, meet weight gain. Weight gain, meet stress
You’re not eating differently and you’re keeping active, but your waistline is expanding. How is that happening? Since eating healthy and exercising shouldn’t make you gain weight, there may be a hidden factor getting in your way. Stress. The one thing that can have a grip on your circadian rhythm stronger than any bodybuilder.
Investigators at Weill Cornell Medicine published two mouse studies that suggest stress and other factors that throw the body’s circadian clocks out of rhythm may contribute to weight gain.
In the first study, the researchers imitated disruptive condition effects like high cortisol exposure and chronic stress by implanting pellets under the skin that released glucocorticoid at a constant rate for 21 days. Mice that received the pellets had twice as much white and brown fat, as well as much higher insulin levels, regardless of their unchanged and still-healthy diet.
In the second study, they used tagged proteins as markers to monitor the daily fluctuations of a protein that regulates fat cell production and circadian gene expression in mouse fat cell precursors. The results showed “that fat cell precursors commit to becoming fat cells only during the circadian cycle phase corresponding to evening in humans,” they said in a written statement.
“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” said senior author Mary Teruel of Cornell University. “A lot of forces are working against a healthy metabolism when we are out of circadian rhythm. The more we understand, the more likely we will be able to do something about it.”
So if you’re stressing out that the scale is or isn’t moving in the direction you want, you could be standing in your own way. Take a chill pill.
Who can smell cancer? The locust nose
If you need to smell some gas, there’s nothing better than a nose. Just ask a scientist: “Noses are still state of the art,” said Debajit Saha, PhD, of Michigan State University. “There’s really nothing like them when it comes to gas sensing.”
And when it comes to noses, dogs are best, right? After all, there’s a reason we don’t have bomb-sniffing wombats and drug-sniffing ostriches. Dogs are better. Better, but not perfect. And if they’re not perfect, then human technology can do better.
Enter the electronic nose. Which is better than dogs … except that it isn’t. “People have been working on ‘electronic noses’ for more than 15 years, but they’re still not close to achieving what biology can do seamlessly,” Dr. Saha explained in a statement from the university.
Which brings us back to dogs. If you want to detect early-stage cancer using smell, you go to the dogs, right? Nope.
Here’s Christopher Contag, PhD, also of Michigan State, who recruited Dr. Saha to the university: “I told him, ‘When you come here, we’ll detect cancer. I’m sure your locusts can do it.’ ”
Yes, locusts. Dr. Contag and his research team were looking at mouth cancers and noticed that different cell lines had different appearances. Then they discovered that those different-looking cell lines produced different metabolites, some of which were volatile.
Enter Dr. Saha’s locusts. They were able to tell the difference between normal cells and cancer cells and could even distinguish between the different cell lines. And how they were able to share this information? Not voluntarily, that’s for sure. The researchers attached electrodes to the insects’ brains and recorded their responses to gas samples from both healthy and cancer cells. Those brain signals were then used to create chemical profiles of the different cells. Piece of cake.
The whole getting-electrodes-attached-to-their-brains thing seemed at least a bit ethically ambiguous, so we contacted the locusts’ PR office, which offered some positive spin: “Humans get their early cancer detection and we get that whole swarms-that-devour-entire-countrysides thing off our backs. Win win.”
Bad news for vampires everywhere
Pop culture has been extraordinarily kind to the vampire. A few hundred years ago, vampires were demon-possessed, often-inhuman monsters. Now? They’re suave, sophisticated, beautiful, and oh-so dramatic and angst-filled about their “curse.” Drink a little human blood, live and look young forever. Such monsters they are.
It does make sense in a morbid sort of way. An old person receiving the blood of the young does seem like a good idea for rejuvenation, right? A team of Ukrainian researchers sought to find out, conducting a study in which older mice were linked with young mice via heterochronic parabiosis. For 3 months, old-young mice pairs were surgically connected and shared blood. After 3 months, the mice were disconnected from each other and the effects of the blood link were studied.
For all the vampire enthusiasts out there, we have bad news and worse news. The bad news first: The older mice received absolutely no benefit from heterochronic parabiosis. No youthfulness, no increased lifespan, nothing. The worse news is that the younger mice were adversely affected by the older blood. They aged more and experienced a shortened lifespan, even after the connection was severed. The old blood, according to the investigators, contains factors capable of inducing aging in younger mice, but the opposite is not true. Further research into aging, they added, should focus on suppressing the aging factors in older blood.
Of note, the paper was written by doctors who are currently refugees, fleeing the war in Ukraine. We don’t want to speculate on the true cause of the war, but we’re onto you, Putin. We know you wanted the vampire research for yourself, but it won’t work. Your dream of becoming Vlad “Dracula” Putin will never come to pass.
Hearing is not always believing
Have you ever heard yourself on a voice mail, or from a recording you did at work? No matter how good you sound, you still might feel like the recording sounds nothing like you. It may even cause low self-esteem for those who don’t like how their voice sounds or don’t recognize it when it’s played back to them.
Since one possible symptom of schizophrenia is not recognizing one’s own speech and having a false sense of control over actions, and those with schizophrenia may hallucinate or hear voices, not being able to recognize their own voices may be alarming.
A recent study on the sense of agency, or sense of control, involved having volunteers speak with different pitches in their voices and then having it played back to them to gauge their reactions.
“Our results demonstrate that hearing one’s own voice is a critical factor to increased self-agency over speech. In other words, we do not strongly feel that ‘I’ am generating the speech if we hear someone else’s voice as an outcome of the speech. Our study provides empirical evidence of the tight link between the sense of agency and self-voice identity,” lead author Ryu Ohata, PhD, of the University of Tokyo, said in a written statement.
As social interaction becomes more digital through platforms such as FaceTime, Zoom, and voicemail, especially since the pandemic has promoted social distancing, it makes sense that people may be more aware and more surprised by how they sound on recordings.
So, if you ever promised someone something that you don’t want to do, and they play it back to you from the recording you made, maybe you can just say you don’t recognize the voice. And if it’s not you, then you don’t have to do it.
Stress, meet weight gain. Weight gain, meet stress
You’re not eating differently and you’re keeping active, but your waistline is expanding. How is that happening? Since eating healthy and exercising shouldn’t make you gain weight, there may be a hidden factor getting in your way. Stress. The one thing that can have a grip on your circadian rhythm stronger than any bodybuilder.
Investigators at Weill Cornell Medicine published two mouse studies that suggest stress and other factors that throw the body’s circadian clocks out of rhythm may contribute to weight gain.
In the first study, the researchers imitated disruptive condition effects like high cortisol exposure and chronic stress by implanting pellets under the skin that released glucocorticoid at a constant rate for 21 days. Mice that received the pellets had twice as much white and brown fat, as well as much higher insulin levels, regardless of their unchanged and still-healthy diet.
In the second study, they used tagged proteins as markers to monitor the daily fluctuations of a protein that regulates fat cell production and circadian gene expression in mouse fat cell precursors. The results showed “that fat cell precursors commit to becoming fat cells only during the circadian cycle phase corresponding to evening in humans,” they said in a written statement.
“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” said senior author Mary Teruel of Cornell University. “A lot of forces are working against a healthy metabolism when we are out of circadian rhythm. The more we understand, the more likely we will be able to do something about it.”
So if you’re stressing out that the scale is or isn’t moving in the direction you want, you could be standing in your own way. Take a chill pill.
Who can smell cancer? The locust nose
If you need to smell some gas, there’s nothing better than a nose. Just ask a scientist: “Noses are still state of the art,” said Debajit Saha, PhD, of Michigan State University. “There’s really nothing like them when it comes to gas sensing.”
And when it comes to noses, dogs are best, right? After all, there’s a reason we don’t have bomb-sniffing wombats and drug-sniffing ostriches. Dogs are better. Better, but not perfect. And if they’re not perfect, then human technology can do better.
Enter the electronic nose. Which is better than dogs … except that it isn’t. “People have been working on ‘electronic noses’ for more than 15 years, but they’re still not close to achieving what biology can do seamlessly,” Dr. Saha explained in a statement from the university.
Which brings us back to dogs. If you want to detect early-stage cancer using smell, you go to the dogs, right? Nope.
Here’s Christopher Contag, PhD, also of Michigan State, who recruited Dr. Saha to the university: “I told him, ‘When you come here, we’ll detect cancer. I’m sure your locusts can do it.’ ”
Yes, locusts. Dr. Contag and his research team were looking at mouth cancers and noticed that different cell lines had different appearances. Then they discovered that those different-looking cell lines produced different metabolites, some of which were volatile.
Enter Dr. Saha’s locusts. They were able to tell the difference between normal cells and cancer cells and could even distinguish between the different cell lines. And how they were able to share this information? Not voluntarily, that’s for sure. The researchers attached electrodes to the insects’ brains and recorded their responses to gas samples from both healthy and cancer cells. Those brain signals were then used to create chemical profiles of the different cells. Piece of cake.
The whole getting-electrodes-attached-to-their-brains thing seemed at least a bit ethically ambiguous, so we contacted the locusts’ PR office, which offered some positive spin: “Humans get their early cancer detection and we get that whole swarms-that-devour-entire-countrysides thing off our backs. Win win.”
Bad news for vampires everywhere
Pop culture has been extraordinarily kind to the vampire. A few hundred years ago, vampires were demon-possessed, often-inhuman monsters. Now? They’re suave, sophisticated, beautiful, and oh-so dramatic and angst-filled about their “curse.” Drink a little human blood, live and look young forever. Such monsters they are.
It does make sense in a morbid sort of way. An old person receiving the blood of the young does seem like a good idea for rejuvenation, right? A team of Ukrainian researchers sought to find out, conducting a study in which older mice were linked with young mice via heterochronic parabiosis. For 3 months, old-young mice pairs were surgically connected and shared blood. After 3 months, the mice were disconnected from each other and the effects of the blood link were studied.
For all the vampire enthusiasts out there, we have bad news and worse news. The bad news first: The older mice received absolutely no benefit from heterochronic parabiosis. No youthfulness, no increased lifespan, nothing. The worse news is that the younger mice were adversely affected by the older blood. They aged more and experienced a shortened lifespan, even after the connection was severed. The old blood, according to the investigators, contains factors capable of inducing aging in younger mice, but the opposite is not true. Further research into aging, they added, should focus on suppressing the aging factors in older blood.
Of note, the paper was written by doctors who are currently refugees, fleeing the war in Ukraine. We don’t want to speculate on the true cause of the war, but we’re onto you, Putin. We know you wanted the vampire research for yourself, but it won’t work. Your dream of becoming Vlad “Dracula” Putin will never come to pass.
Hearing is not always believing
Have you ever heard yourself on a voice mail, or from a recording you did at work? No matter how good you sound, you still might feel like the recording sounds nothing like you. It may even cause low self-esteem for those who don’t like how their voice sounds or don’t recognize it when it’s played back to them.
Since one possible symptom of schizophrenia is not recognizing one’s own speech and having a false sense of control over actions, and those with schizophrenia may hallucinate or hear voices, not being able to recognize their own voices may be alarming.
A recent study on the sense of agency, or sense of control, involved having volunteers speak with different pitches in their voices and then having it played back to them to gauge their reactions.
“Our results demonstrate that hearing one’s own voice is a critical factor to increased self-agency over speech. In other words, we do not strongly feel that ‘I’ am generating the speech if we hear someone else’s voice as an outcome of the speech. Our study provides empirical evidence of the tight link between the sense of agency and self-voice identity,” lead author Ryu Ohata, PhD, of the University of Tokyo, said in a written statement.
As social interaction becomes more digital through platforms such as FaceTime, Zoom, and voicemail, especially since the pandemic has promoted social distancing, it makes sense that people may be more aware and more surprised by how they sound on recordings.
So, if you ever promised someone something that you don’t want to do, and they play it back to you from the recording you made, maybe you can just say you don’t recognize the voice. And if it’s not you, then you don’t have to do it.
Stress, meet weight gain. Weight gain, meet stress
You’re not eating differently and you’re keeping active, but your waistline is expanding. How is that happening? Since eating healthy and exercising shouldn’t make you gain weight, there may be a hidden factor getting in your way. Stress. The one thing that can have a grip on your circadian rhythm stronger than any bodybuilder.
Investigators at Weill Cornell Medicine published two mouse studies that suggest stress and other factors that throw the body’s circadian clocks out of rhythm may contribute to weight gain.
In the first study, the researchers imitated disruptive condition effects like high cortisol exposure and chronic stress by implanting pellets under the skin that released glucocorticoid at a constant rate for 21 days. Mice that received the pellets had twice as much white and brown fat, as well as much higher insulin levels, regardless of their unchanged and still-healthy diet.
In the second study, they used tagged proteins as markers to monitor the daily fluctuations of a protein that regulates fat cell production and circadian gene expression in mouse fat cell precursors. The results showed “that fat cell precursors commit to becoming fat cells only during the circadian cycle phase corresponding to evening in humans,” they said in a written statement.
“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” said senior author Mary Teruel of Cornell University. “A lot of forces are working against a healthy metabolism when we are out of circadian rhythm. The more we understand, the more likely we will be able to do something about it.”
So if you’re stressing out that the scale is or isn’t moving in the direction you want, you could be standing in your own way. Take a chill pill.
Who can smell cancer? The locust nose
If you need to smell some gas, there’s nothing better than a nose. Just ask a scientist: “Noses are still state of the art,” said Debajit Saha, PhD, of Michigan State University. “There’s really nothing like them when it comes to gas sensing.”
And when it comes to noses, dogs are best, right? After all, there’s a reason we don’t have bomb-sniffing wombats and drug-sniffing ostriches. Dogs are better. Better, but not perfect. And if they’re not perfect, then human technology can do better.
Enter the electronic nose. Which is better than dogs … except that it isn’t. “People have been working on ‘electronic noses’ for more than 15 years, but they’re still not close to achieving what biology can do seamlessly,” Dr. Saha explained in a statement from the university.
Which brings us back to dogs. If you want to detect early-stage cancer using smell, you go to the dogs, right? Nope.
Here’s Christopher Contag, PhD, also of Michigan State, who recruited Dr. Saha to the university: “I told him, ‘When you come here, we’ll detect cancer. I’m sure your locusts can do it.’ ”
Yes, locusts. Dr. Contag and his research team were looking at mouth cancers and noticed that different cell lines had different appearances. Then they discovered that those different-looking cell lines produced different metabolites, some of which were volatile.
Enter Dr. Saha’s locusts. They were able to tell the difference between normal cells and cancer cells and could even distinguish between the different cell lines. And how they were able to share this information? Not voluntarily, that’s for sure. The researchers attached electrodes to the insects’ brains and recorded their responses to gas samples from both healthy and cancer cells. Those brain signals were then used to create chemical profiles of the different cells. Piece of cake.
The whole getting-electrodes-attached-to-their-brains thing seemed at least a bit ethically ambiguous, so we contacted the locusts’ PR office, which offered some positive spin: “Humans get their early cancer detection and we get that whole swarms-that-devour-entire-countrysides thing off our backs. Win win.”
Bad news for vampires everywhere
Pop culture has been extraordinarily kind to the vampire. A few hundred years ago, vampires were demon-possessed, often-inhuman monsters. Now? They’re suave, sophisticated, beautiful, and oh-so dramatic and angst-filled about their “curse.” Drink a little human blood, live and look young forever. Such monsters they are.
It does make sense in a morbid sort of way. An old person receiving the blood of the young does seem like a good idea for rejuvenation, right? A team of Ukrainian researchers sought to find out, conducting a study in which older mice were linked with young mice via heterochronic parabiosis. For 3 months, old-young mice pairs were surgically connected and shared blood. After 3 months, the mice were disconnected from each other and the effects of the blood link were studied.
For all the vampire enthusiasts out there, we have bad news and worse news. The bad news first: The older mice received absolutely no benefit from heterochronic parabiosis. No youthfulness, no increased lifespan, nothing. The worse news is that the younger mice were adversely affected by the older blood. They aged more and experienced a shortened lifespan, even after the connection was severed. The old blood, according to the investigators, contains factors capable of inducing aging in younger mice, but the opposite is not true. Further research into aging, they added, should focus on suppressing the aging factors in older blood.
Of note, the paper was written by doctors who are currently refugees, fleeing the war in Ukraine. We don’t want to speculate on the true cause of the war, but we’re onto you, Putin. We know you wanted the vampire research for yourself, but it won’t work. Your dream of becoming Vlad “Dracula” Putin will never come to pass.
Hearing is not always believing
Have you ever heard yourself on a voice mail, or from a recording you did at work? No matter how good you sound, you still might feel like the recording sounds nothing like you. It may even cause low self-esteem for those who don’t like how their voice sounds or don’t recognize it when it’s played back to them.
Since one possible symptom of schizophrenia is not recognizing one’s own speech and having a false sense of control over actions, and those with schizophrenia may hallucinate or hear voices, not being able to recognize their own voices may be alarming.
A recent study on the sense of agency, or sense of control, involved having volunteers speak with different pitches in their voices and then having it played back to them to gauge their reactions.
“Our results demonstrate that hearing one’s own voice is a critical factor to increased self-agency over speech. In other words, we do not strongly feel that ‘I’ am generating the speech if we hear someone else’s voice as an outcome of the speech. Our study provides empirical evidence of the tight link between the sense of agency and self-voice identity,” lead author Ryu Ohata, PhD, of the University of Tokyo, said in a written statement.
As social interaction becomes more digital through platforms such as FaceTime, Zoom, and voicemail, especially since the pandemic has promoted social distancing, it makes sense that people may be more aware and more surprised by how they sound on recordings.
So, if you ever promised someone something that you don’t want to do, and they play it back to you from the recording you made, maybe you can just say you don’t recognize the voice. And if it’s not you, then you don’t have to do it.
NAFLD linked with increased heart failure risk
The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.
The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.
“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.
“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”
The study was published online in Gut.
Risk calculations
NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.
Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.
Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.
The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.
In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.
Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.
The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.
In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.
“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.
“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
Future research
Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.
But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.
“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.
Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.
Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.
“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”
The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.
The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.
“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.
“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”
The study was published online in Gut.
Risk calculations
NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.
Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.
Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.
The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.
In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.
Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.
The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.
In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.
“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.
“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
Future research
Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.
But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.
“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.
Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.
Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.
“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”
The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.
The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.
“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.
“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”
The study was published online in Gut.
Risk calculations
NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.
Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.
Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.
The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.
In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.
Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.
The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.
In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.
“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.
“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
Future research
Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.
But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.
“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.
Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.
Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.
“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”
The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM GUT
Monkeypox: Another emerging threat?
CASE Pregnant woman’s husband is ill after traveling
A 29-year-old primigravid woman at 18 weeks’ gestation just returned from a 10-day trip to Nigeria with her husband. While in Nigeria, the couple went on safari. On several occasions during the safari, they consumed bushmeat prepared by their guides. Her husband now has severe malaise, fever, chills, myalgias, cough, and prominent submandibular, cervical, and inguinal adenopathy. In addition, he has developed a diffuse papular-vesicular rash on his trunk and extremities.
- What is the most likely diagnosis?
- Does this condition pose a danger to his wife?
- What treatment is indicated for his wife?
What we know
In recent weeks, the specter of another poorly understood biological threat has emerged in the medical literature and lay press: monkeypox. This article will first review the epidemiology, clinical manifestations, and diagnosis of this infection, followed by a discussion of how to prevent and treat the condition, with special emphasis on the risks that this infection poses in pregnant women.
Virology
The monkeypox virus is a member of the orthopoxvirus genus. The variola (smallpox) virus and vaccinia virus are included in this genus. It is one of the largest of all viruses, measuring 200-250 nm. It is enveloped and contains double-stranded DNA. Its natural reservoir is probably African rodents. Two distinct strains of monkeypox exist in different geographical regions of Africa: the Central African clade and the West African clade. The Central African clade is significantly more virulent than the latter, with a mortality rate approaching 10%, versus 1% in the West African clade. The incubation period of the virus ranges from 4-20 days and averages 12 days.1,2
Epidemiology
Monkeypox was first discovered in 1958 by Preben von Magnus in a colony of research monkeys in Copenhagen, Denmark. The first case of monkeypox in humans occurred in the Democratic Republic of Congo in 1970 in a 9-year-old boy. Subsequently, cases were reported in the Ivory Coast, Liberia, Nigeria, and Sierra Leone. The infection was limited to the rain forests of central and western Africa until 2003. At that time, the first cases in the United States were reported. The US cases occurred in the Midwest and were traced to exposure to pet prairie dogs. These animals all came from a single distributor, and they apparently were infected when they were housed in the same space with Gambian rats, which are well recognized reservoirs of monkeypox in their native habitat in Africa.1-3
A limited outbreak of monkeypox occurred in the United Kingdom in 2018. Seventy-one cases, with no fatalities, were reported. In 2021 another US case of monkeypox was reported in Dallas, Texas, in an individual who had recently traveled to the United States from Nigeria. A second US case was reported in November 2021 from a patient in Maryland who had returned from a visit to Nigeria. Those were the only 2 reported cases of monkeypox in the United States in 2021.1-3
Then in early May 2022, the United Kingdom reported 9 cases of monkeypox. The first infected patient had recently traveled to Nigeria and, subsequently, infected 2 members of his family.4 On May 18, the Massachusetts Department of Public Health confirmed a case of monkeypox in an adult man who had recently traveled to Canada. As of July 7, 6,027 cases have been reported from at least 39 countries.
The current outbreak is unusual in that, previously, almost all cases occurred in western and central Africa in remote tropical rain forests. Infection usually resulted from close exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Exposure occurred when persons captured, slaughtered, prepared, and then ate these animals for food without properly cooking the flesh.
The leading theory is that the present outbreak originated among men who had sex with men at 2 raves held in Spain and Belgium. The virus appears to have been spread by skin-to-skin contact, by respiratory droplets, by contact with contaminated bedding, and probably by sperm.2,4,6
Continue to: Clinical manifestations...
Clinical manifestations
Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.1
Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.7
Diagnosis
The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.
In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.1
The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.1
When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.8
How do we manage monkeypox?
Prevention
The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.
The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.7,9
The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.10 This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.7,9
There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.
- Monkeypox is a member of the orthopoxvirus genus and is closely related to the smallpox virus. It is a large, double-stranded, enveloped DNA virus.
- The virus is transmitted primarily by close contact with infected animals or other humans or by consumption of contaminated bushmeat.
- The infection evolves in 2 phases. The pre-eruptive phase is characterized by severe flu-like symptoms and signs. The eruptive phase is distinguished by a diffuse papular-vesicular rash.
- The most valuable test for confirming the diagnosis is a polymerase chain reaction test of a fresh skin lesion.
- In women who are pregnant, monkeypox has been associated with spontaneous abortion and fetal death.
- Three antiviral agents may be of value in treating infected patients: cidofovir, brincidofovir, and tecovirimat. Only the latter has an acceptable safety profile for women who are pregnant or lactating.
- The new nonreplicating smallpox vaccine Jynneos (Bavarian Nordic A/S) is of great value for pre- and post-exposure prophylaxis.
Continue to: Treatment...
Treatment
Infected pregnant women should receive acetaminophen 1,000 mg orally every 8 hours, to control fever and provide analgesia. An antihistamine such as diphenhydramine 25 mg orally every 6-8 hours, may be used to control pruritus and provide mild sedation. Adequate fluid intake and optimal nutrition should be encouraged. Skin lesions should be inspected regularly to detect signs of superimposed bacterial infections. Small, localized bacterial skin infections can be treated with topical application of mupirocin ointment 2%, 3 times daily for 7-14 days. For diffuse and more severe bacterial skin infections, a systemic antibiotic may be necessary. Reasonable choices include amoxicillin-clavulanate 875 mg/125 mg orally every 12 hours, or trimethoprim-sulfamethoxazole double strength 800 mg/160 mg orally every 12 hours.11 The latter agent should be avoided in the first trimester of pregnancy because of potential teratogenic effects.
Several specific agents are available through the CDC for treatment of orthopoxvirus infections such as smallpox and monkeypox. Information about these agents is summarized in the TABLE.12-16
Unique considerations in pregnancy
Because monkeypox is so rare, there is very little information about the effects of this infection in pregnant women. The report most commonly cited in the literature is that by Mbala et al, which was published in 2017.17 These authors described 4 pregnant patients in the Democratic Republic of Congo who contracted monkeypox infection over a 4-year period. All 4 women were hospitalized and treated with systemic antibiotics, antiparasitic medications, and analgesics. One patient delivered a healthy infant. Two women had spontaneous abortions in the first trimester. The fourth patient experienced a stillbirth at 22 weeks’ gestation. At postmortem examination, the fetus had diffuse cutaneous lesions, prominent hepatomegaly, and hydrops. No structural malformations were noted. The placenta demonstrated numerous punctate hemorrhages, and high concentrations of virus were recovered from the placenta and from fetal tissue.
Although the information on pregnancy outcome is quite limited, it seems clear that the virus can cross the placenta and cause adverse effects such as spontaneous abortion and fetal death. Accordingly, I think the following guidelines are a reasonable approach to a pregnant patient who has been exposed to monkeypox or who has developed manifestations of infection.3,7,9
- In the event of a community outbreak, bioterrorism event, or exposure to a person with suspected or confirmed monkeypox infection, the pregnant patient should receive the Jynneos vaccine.
- The pregnant patient should be isolated from any individual with suspected or confirmed monkeypox.
- If infection develops despite these measures, the patient should be treated with either tecovirimat or vaccinia immune globulin IV. Hospitalization may be necessary for seriously ill individuals.
- Within 2 weeks of infection, a comprehensive ultrasound examination should be performed to assess for structural abnormalities in the fetus.
- Subsequently, serial ultrasound examinations should be performed at intervals of 4-6 weeks to assess fetal growth and re-evaluate fetal anatomy.
- Following delivery, a detailed neonatal examination should be performed to assess for evidence of viral injury. Neonatal skin lesions and neonatal serum can be assessed by PCR for monkeypox virus. The newborn should be isolated from the mother until all the mother’s lesions have dried and crusted over.
CASE Resolved
Given the husband’s recent travel to Nigeria and consumption of bushmeat, he most likely has monkeypox. The infection can be spread from person to person by close contact; thus, his wife is at risk. The couple should isolate until all of his lesions have dried and crusted over. The woman also should receive the Jynneos vaccine. If she becomes symptomatic, she should be treated with tecovirimat or vaccinia immune globulin IV. ●
- Isaacs SN, Shenoy ES. Monkeypox. UpToDate. Updated June 28,2022. Accessed July 1, 2022. https://www.uptodate.com /contents/monkeypox?topicRef=8349&source=see_link
- Graham MB. Monkeypox. Medscape. Updated June 29, 2022. Accessed July 1, 2022. https://emedicine.medscape.com /article/1134714-overview.
- Khalil A, Samara A, O’Brien P, et al. Monkeypox and pregnancy: what do obstetricians need to know? Ultrasound Obstet Gynecol. 2022;60:22-27. doi:10.1002/uog.24968.
- World Health Organization. Monkeypox-United Kingdom of Great Britain and Northern Ireland. May 18, 2022. Accessed July 1, 2022. https://www.who.int/emergencies/diseaseoutbreak-news/item/2022-DON383.
- WHO reports two new monkeypox deaths, cases in new areas. Reuters. July 7, 2022. https://www.reuters.com/world /who-reports-two-new-monkeypox-deaths-2022-07-07/. Accessed July 19, 2022.
- World Health Organization. Multi-country monkeypox outbreak in non-endemic countries: update. May 29, 2022. Accessed July 1, 2022. https://www.who.int /emergencies/disease-outbreak-news/item/2022 -DON388#:~:text=Multi%2Dcountry%20monkeypox%20 outbreak%20in%20non%2Dendemic%20countries%3A%20 Update,-29%20May%202022&text=Since%2013%20 May%202022%2C%20monkeypox,Epidemiological%20 investigations%20are%20ongoing.
- Cono J, Cragan JD, Jamieson DJ, Rasmussen SA. Prophylaxis and treatment of pregnant women for emerging infections andbioterrorism emergencies. Emerg Infect Dis. 2006;12:16311637. doi:10.3201/eid1211.060618.
- Centers for Disease Control and Prevention. Preparation and collection of specimens. Reviewed June 29, 2022. Accessed July 6, 2022. https://www.cdc.gov/poxvirus /monkeypox/clinicians/prep-collection-specimens.html.
- Rao AK, Petersen BW, Whitehill F, et al. Monkeypox vaccination. MMWR Morb Mortal Wkly Rep. 2022;71:734-742. doi:10.15585/mmwr.mm7122e1.
- Smallpox and monkeypox vaccine, live, nonreplicating. Package insert. Bavarian Nordic A/S; 2021. Accessed July 1, 2022. https://www.fda.gov/media/131078/download.
- Duff P. Commonly used antibiotics in ObGyn practice. OBG Manag. 2022;34:29, 36-40. doi:10.12788/obgm.0191.
- Centers for Disease Control and Prevention. Treatment information for healthcare professionals: interim clinical guidance for the treatment of monkeypox. Reviewed June 17, 2022. Accessed July 1, 2022. https://www.cdc.gov/poxvirus /monkeypox/clinicians/treatment.html.
- Brincidofovir. Prescribing information. Chimerix, Inc.; 2021. Accessed July 1, 2022. https://www.accessdata.fda.gov /drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf.
- Cidofovir. Package insert. Gilead Sciences, Inc.; 2010. Accessed July 1, 2022. https://www.gilead.com/~/media /Files/pdfs/medicines/other/vistide/vistide.pdf.
- Tecovirimat. Prescribing information. Catalent Pharma Solutions; 2022. Accessed July 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs /label/2022/214518s000lbl.pdf.
- Vaccinia immune globulin IV. Prescribing information. Cangene Corporation; 2010. Accessed July 1, 2022. https: //www.fda.gov/media/77004/download.
- Mbala PK, Huggins JW, Riu-Rovira T, et al. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infect Dis. 2017;216:824-828. doi:10.1093/infdis/jix260.
Dr. Duff is Professor, Maternal-Fetal Medicine, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida.
The author reports no financial relationships relevant to this article.
Dr. Duff is Professor, Maternal-Fetal Medicine, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida.
The author reports no financial relationships relevant to this article.
Dr. Duff is Professor, Maternal-Fetal Medicine, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida.
The author reports no financial relationships relevant to this article.
CASE Pregnant woman’s husband is ill after traveling
A 29-year-old primigravid woman at 18 weeks’ gestation just returned from a 10-day trip to Nigeria with her husband. While in Nigeria, the couple went on safari. On several occasions during the safari, they consumed bushmeat prepared by their guides. Her husband now has severe malaise, fever, chills, myalgias, cough, and prominent submandibular, cervical, and inguinal adenopathy. In addition, he has developed a diffuse papular-vesicular rash on his trunk and extremities.
- What is the most likely diagnosis?
- Does this condition pose a danger to his wife?
- What treatment is indicated for his wife?
What we know
In recent weeks, the specter of another poorly understood biological threat has emerged in the medical literature and lay press: monkeypox. This article will first review the epidemiology, clinical manifestations, and diagnosis of this infection, followed by a discussion of how to prevent and treat the condition, with special emphasis on the risks that this infection poses in pregnant women.
Virology
The monkeypox virus is a member of the orthopoxvirus genus. The variola (smallpox) virus and vaccinia virus are included in this genus. It is one of the largest of all viruses, measuring 200-250 nm. It is enveloped and contains double-stranded DNA. Its natural reservoir is probably African rodents. Two distinct strains of monkeypox exist in different geographical regions of Africa: the Central African clade and the West African clade. The Central African clade is significantly more virulent than the latter, with a mortality rate approaching 10%, versus 1% in the West African clade. The incubation period of the virus ranges from 4-20 days and averages 12 days.1,2
Epidemiology
Monkeypox was first discovered in 1958 by Preben von Magnus in a colony of research monkeys in Copenhagen, Denmark. The first case of monkeypox in humans occurred in the Democratic Republic of Congo in 1970 in a 9-year-old boy. Subsequently, cases were reported in the Ivory Coast, Liberia, Nigeria, and Sierra Leone. The infection was limited to the rain forests of central and western Africa until 2003. At that time, the first cases in the United States were reported. The US cases occurred in the Midwest and were traced to exposure to pet prairie dogs. These animals all came from a single distributor, and they apparently were infected when they were housed in the same space with Gambian rats, which are well recognized reservoirs of monkeypox in their native habitat in Africa.1-3
A limited outbreak of monkeypox occurred in the United Kingdom in 2018. Seventy-one cases, with no fatalities, were reported. In 2021 another US case of monkeypox was reported in Dallas, Texas, in an individual who had recently traveled to the United States from Nigeria. A second US case was reported in November 2021 from a patient in Maryland who had returned from a visit to Nigeria. Those were the only 2 reported cases of monkeypox in the United States in 2021.1-3
Then in early May 2022, the United Kingdom reported 9 cases of monkeypox. The first infected patient had recently traveled to Nigeria and, subsequently, infected 2 members of his family.4 On May 18, the Massachusetts Department of Public Health confirmed a case of monkeypox in an adult man who had recently traveled to Canada. As of July 7, 6,027 cases have been reported from at least 39 countries.
The current outbreak is unusual in that, previously, almost all cases occurred in western and central Africa in remote tropical rain forests. Infection usually resulted from close exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Exposure occurred when persons captured, slaughtered, prepared, and then ate these animals for food without properly cooking the flesh.
The leading theory is that the present outbreak originated among men who had sex with men at 2 raves held in Spain and Belgium. The virus appears to have been spread by skin-to-skin contact, by respiratory droplets, by contact with contaminated bedding, and probably by sperm.2,4,6
Continue to: Clinical manifestations...
Clinical manifestations
Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.1
Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.7
Diagnosis
The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.
In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.1
The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.1
When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.8
How do we manage monkeypox?
Prevention
The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.
The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.7,9
The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.10 This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.7,9
There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.
- Monkeypox is a member of the orthopoxvirus genus and is closely related to the smallpox virus. It is a large, double-stranded, enveloped DNA virus.
- The virus is transmitted primarily by close contact with infected animals or other humans or by consumption of contaminated bushmeat.
- The infection evolves in 2 phases. The pre-eruptive phase is characterized by severe flu-like symptoms and signs. The eruptive phase is distinguished by a diffuse papular-vesicular rash.
- The most valuable test for confirming the diagnosis is a polymerase chain reaction test of a fresh skin lesion.
- In women who are pregnant, monkeypox has been associated with spontaneous abortion and fetal death.
- Three antiviral agents may be of value in treating infected patients: cidofovir, brincidofovir, and tecovirimat. Only the latter has an acceptable safety profile for women who are pregnant or lactating.
- The new nonreplicating smallpox vaccine Jynneos (Bavarian Nordic A/S) is of great value for pre- and post-exposure prophylaxis.
Continue to: Treatment...
Treatment
Infected pregnant women should receive acetaminophen 1,000 mg orally every 8 hours, to control fever and provide analgesia. An antihistamine such as diphenhydramine 25 mg orally every 6-8 hours, may be used to control pruritus and provide mild sedation. Adequate fluid intake and optimal nutrition should be encouraged. Skin lesions should be inspected regularly to detect signs of superimposed bacterial infections. Small, localized bacterial skin infections can be treated with topical application of mupirocin ointment 2%, 3 times daily for 7-14 days. For diffuse and more severe bacterial skin infections, a systemic antibiotic may be necessary. Reasonable choices include amoxicillin-clavulanate 875 mg/125 mg orally every 12 hours, or trimethoprim-sulfamethoxazole double strength 800 mg/160 mg orally every 12 hours.11 The latter agent should be avoided in the first trimester of pregnancy because of potential teratogenic effects.
Several specific agents are available through the CDC for treatment of orthopoxvirus infections such as smallpox and monkeypox. Information about these agents is summarized in the TABLE.12-16
Unique considerations in pregnancy
Because monkeypox is so rare, there is very little information about the effects of this infection in pregnant women. The report most commonly cited in the literature is that by Mbala et al, which was published in 2017.17 These authors described 4 pregnant patients in the Democratic Republic of Congo who contracted monkeypox infection over a 4-year period. All 4 women were hospitalized and treated with systemic antibiotics, antiparasitic medications, and analgesics. One patient delivered a healthy infant. Two women had spontaneous abortions in the first trimester. The fourth patient experienced a stillbirth at 22 weeks’ gestation. At postmortem examination, the fetus had diffuse cutaneous lesions, prominent hepatomegaly, and hydrops. No structural malformations were noted. The placenta demonstrated numerous punctate hemorrhages, and high concentrations of virus were recovered from the placenta and from fetal tissue.
Although the information on pregnancy outcome is quite limited, it seems clear that the virus can cross the placenta and cause adverse effects such as spontaneous abortion and fetal death. Accordingly, I think the following guidelines are a reasonable approach to a pregnant patient who has been exposed to monkeypox or who has developed manifestations of infection.3,7,9
- In the event of a community outbreak, bioterrorism event, or exposure to a person with suspected or confirmed monkeypox infection, the pregnant patient should receive the Jynneos vaccine.
- The pregnant patient should be isolated from any individual with suspected or confirmed monkeypox.
- If infection develops despite these measures, the patient should be treated with either tecovirimat or vaccinia immune globulin IV. Hospitalization may be necessary for seriously ill individuals.
- Within 2 weeks of infection, a comprehensive ultrasound examination should be performed to assess for structural abnormalities in the fetus.
- Subsequently, serial ultrasound examinations should be performed at intervals of 4-6 weeks to assess fetal growth and re-evaluate fetal anatomy.
- Following delivery, a detailed neonatal examination should be performed to assess for evidence of viral injury. Neonatal skin lesions and neonatal serum can be assessed by PCR for monkeypox virus. The newborn should be isolated from the mother until all the mother’s lesions have dried and crusted over.
CASE Resolved
Given the husband’s recent travel to Nigeria and consumption of bushmeat, he most likely has monkeypox. The infection can be spread from person to person by close contact; thus, his wife is at risk. The couple should isolate until all of his lesions have dried and crusted over. The woman also should receive the Jynneos vaccine. If she becomes symptomatic, she should be treated with tecovirimat or vaccinia immune globulin IV. ●
CASE Pregnant woman’s husband is ill after traveling
A 29-year-old primigravid woman at 18 weeks’ gestation just returned from a 10-day trip to Nigeria with her husband. While in Nigeria, the couple went on safari. On several occasions during the safari, they consumed bushmeat prepared by their guides. Her husband now has severe malaise, fever, chills, myalgias, cough, and prominent submandibular, cervical, and inguinal adenopathy. In addition, he has developed a diffuse papular-vesicular rash on his trunk and extremities.
- What is the most likely diagnosis?
- Does this condition pose a danger to his wife?
- What treatment is indicated for his wife?
What we know
In recent weeks, the specter of another poorly understood biological threat has emerged in the medical literature and lay press: monkeypox. This article will first review the epidemiology, clinical manifestations, and diagnosis of this infection, followed by a discussion of how to prevent and treat the condition, with special emphasis on the risks that this infection poses in pregnant women.
Virology
The monkeypox virus is a member of the orthopoxvirus genus. The variola (smallpox) virus and vaccinia virus are included in this genus. It is one of the largest of all viruses, measuring 200-250 nm. It is enveloped and contains double-stranded DNA. Its natural reservoir is probably African rodents. Two distinct strains of monkeypox exist in different geographical regions of Africa: the Central African clade and the West African clade. The Central African clade is significantly more virulent than the latter, with a mortality rate approaching 10%, versus 1% in the West African clade. The incubation period of the virus ranges from 4-20 days and averages 12 days.1,2
Epidemiology
Monkeypox was first discovered in 1958 by Preben von Magnus in a colony of research monkeys in Copenhagen, Denmark. The first case of monkeypox in humans occurred in the Democratic Republic of Congo in 1970 in a 9-year-old boy. Subsequently, cases were reported in the Ivory Coast, Liberia, Nigeria, and Sierra Leone. The infection was limited to the rain forests of central and western Africa until 2003. At that time, the first cases in the United States were reported. The US cases occurred in the Midwest and were traced to exposure to pet prairie dogs. These animals all came from a single distributor, and they apparently were infected when they were housed in the same space with Gambian rats, which are well recognized reservoirs of monkeypox in their native habitat in Africa.1-3
A limited outbreak of monkeypox occurred in the United Kingdom in 2018. Seventy-one cases, with no fatalities, were reported. In 2021 another US case of monkeypox was reported in Dallas, Texas, in an individual who had recently traveled to the United States from Nigeria. A second US case was reported in November 2021 from a patient in Maryland who had returned from a visit to Nigeria. Those were the only 2 reported cases of monkeypox in the United States in 2021.1-3
Then in early May 2022, the United Kingdom reported 9 cases of monkeypox. The first infected patient had recently traveled to Nigeria and, subsequently, infected 2 members of his family.4 On May 18, the Massachusetts Department of Public Health confirmed a case of monkeypox in an adult man who had recently traveled to Canada. As of July 7, 6,027 cases have been reported from at least 39 countries.
The current outbreak is unusual in that, previously, almost all cases occurred in western and central Africa in remote tropical rain forests. Infection usually resulted from close exposure to rats, rabbits, squirrels, monkeys, porcupines, and gazelles. Exposure occurred when persons captured, slaughtered, prepared, and then ate these animals for food without properly cooking the flesh.
The leading theory is that the present outbreak originated among men who had sex with men at 2 raves held in Spain and Belgium. The virus appears to have been spread by skin-to-skin contact, by respiratory droplets, by contact with contaminated bedding, and probably by sperm.2,4,6
Continue to: Clinical manifestations...
Clinical manifestations
Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.1
Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.7
Diagnosis
The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.
In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.1
The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.1
When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.8
How do we manage monkeypox?
Prevention
The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.
The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.7,9
The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.10 This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.7,9
There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.
- Monkeypox is a member of the orthopoxvirus genus and is closely related to the smallpox virus. It is a large, double-stranded, enveloped DNA virus.
- The virus is transmitted primarily by close contact with infected animals or other humans or by consumption of contaminated bushmeat.
- The infection evolves in 2 phases. The pre-eruptive phase is characterized by severe flu-like symptoms and signs. The eruptive phase is distinguished by a diffuse papular-vesicular rash.
- The most valuable test for confirming the diagnosis is a polymerase chain reaction test of a fresh skin lesion.
- In women who are pregnant, monkeypox has been associated with spontaneous abortion and fetal death.
- Three antiviral agents may be of value in treating infected patients: cidofovir, brincidofovir, and tecovirimat. Only the latter has an acceptable safety profile for women who are pregnant or lactating.
- The new nonreplicating smallpox vaccine Jynneos (Bavarian Nordic A/S) is of great value for pre- and post-exposure prophylaxis.
Continue to: Treatment...
Treatment
Infected pregnant women should receive acetaminophen 1,000 mg orally every 8 hours, to control fever and provide analgesia. An antihistamine such as diphenhydramine 25 mg orally every 6-8 hours, may be used to control pruritus and provide mild sedation. Adequate fluid intake and optimal nutrition should be encouraged. Skin lesions should be inspected regularly to detect signs of superimposed bacterial infections. Small, localized bacterial skin infections can be treated with topical application of mupirocin ointment 2%, 3 times daily for 7-14 days. For diffuse and more severe bacterial skin infections, a systemic antibiotic may be necessary. Reasonable choices include amoxicillin-clavulanate 875 mg/125 mg orally every 12 hours, or trimethoprim-sulfamethoxazole double strength 800 mg/160 mg orally every 12 hours.11 The latter agent should be avoided in the first trimester of pregnancy because of potential teratogenic effects.
Several specific agents are available through the CDC for treatment of orthopoxvirus infections such as smallpox and monkeypox. Information about these agents is summarized in the TABLE.12-16
Unique considerations in pregnancy
Because monkeypox is so rare, there is very little information about the effects of this infection in pregnant women. The report most commonly cited in the literature is that by Mbala et al, which was published in 2017.17 These authors described 4 pregnant patients in the Democratic Republic of Congo who contracted monkeypox infection over a 4-year period. All 4 women were hospitalized and treated with systemic antibiotics, antiparasitic medications, and analgesics. One patient delivered a healthy infant. Two women had spontaneous abortions in the first trimester. The fourth patient experienced a stillbirth at 22 weeks’ gestation. At postmortem examination, the fetus had diffuse cutaneous lesions, prominent hepatomegaly, and hydrops. No structural malformations were noted. The placenta demonstrated numerous punctate hemorrhages, and high concentrations of virus were recovered from the placenta and from fetal tissue.
Although the information on pregnancy outcome is quite limited, it seems clear that the virus can cross the placenta and cause adverse effects such as spontaneous abortion and fetal death. Accordingly, I think the following guidelines are a reasonable approach to a pregnant patient who has been exposed to monkeypox or who has developed manifestations of infection.3,7,9
- In the event of a community outbreak, bioterrorism event, or exposure to a person with suspected or confirmed monkeypox infection, the pregnant patient should receive the Jynneos vaccine.
- The pregnant patient should be isolated from any individual with suspected or confirmed monkeypox.
- If infection develops despite these measures, the patient should be treated with either tecovirimat or vaccinia immune globulin IV. Hospitalization may be necessary for seriously ill individuals.
- Within 2 weeks of infection, a comprehensive ultrasound examination should be performed to assess for structural abnormalities in the fetus.
- Subsequently, serial ultrasound examinations should be performed at intervals of 4-6 weeks to assess fetal growth and re-evaluate fetal anatomy.
- Following delivery, a detailed neonatal examination should be performed to assess for evidence of viral injury. Neonatal skin lesions and neonatal serum can be assessed by PCR for monkeypox virus. The newborn should be isolated from the mother until all the mother’s lesions have dried and crusted over.
CASE Resolved
Given the husband’s recent travel to Nigeria and consumption of bushmeat, he most likely has monkeypox. The infection can be spread from person to person by close contact; thus, his wife is at risk. The couple should isolate until all of his lesions have dried and crusted over. The woman also should receive the Jynneos vaccine. If she becomes symptomatic, she should be treated with tecovirimat or vaccinia immune globulin IV. ●
- Isaacs SN, Shenoy ES. Monkeypox. UpToDate. Updated June 28,2022. Accessed July 1, 2022. https://www.uptodate.com /contents/monkeypox?topicRef=8349&source=see_link
- Graham MB. Monkeypox. Medscape. Updated June 29, 2022. Accessed July 1, 2022. https://emedicine.medscape.com /article/1134714-overview.
- Khalil A, Samara A, O’Brien P, et al. Monkeypox and pregnancy: what do obstetricians need to know? Ultrasound Obstet Gynecol. 2022;60:22-27. doi:10.1002/uog.24968.
- World Health Organization. Monkeypox-United Kingdom of Great Britain and Northern Ireland. May 18, 2022. Accessed July 1, 2022. https://www.who.int/emergencies/diseaseoutbreak-news/item/2022-DON383.
- WHO reports two new monkeypox deaths, cases in new areas. Reuters. July 7, 2022. https://www.reuters.com/world /who-reports-two-new-monkeypox-deaths-2022-07-07/. Accessed July 19, 2022.
- World Health Organization. Multi-country monkeypox outbreak in non-endemic countries: update. May 29, 2022. Accessed July 1, 2022. https://www.who.int /emergencies/disease-outbreak-news/item/2022 -DON388#:~:text=Multi%2Dcountry%20monkeypox%20 outbreak%20in%20non%2Dendemic%20countries%3A%20 Update,-29%20May%202022&text=Since%2013%20 May%202022%2C%20monkeypox,Epidemiological%20 investigations%20are%20ongoing.
- Cono J, Cragan JD, Jamieson DJ, Rasmussen SA. Prophylaxis and treatment of pregnant women for emerging infections andbioterrorism emergencies. Emerg Infect Dis. 2006;12:16311637. doi:10.3201/eid1211.060618.
- Centers for Disease Control and Prevention. Preparation and collection of specimens. Reviewed June 29, 2022. Accessed July 6, 2022. https://www.cdc.gov/poxvirus /monkeypox/clinicians/prep-collection-specimens.html.
- Rao AK, Petersen BW, Whitehill F, et al. Monkeypox vaccination. MMWR Morb Mortal Wkly Rep. 2022;71:734-742. doi:10.15585/mmwr.mm7122e1.
- Smallpox and monkeypox vaccine, live, nonreplicating. Package insert. Bavarian Nordic A/S; 2021. Accessed July 1, 2022. https://www.fda.gov/media/131078/download.
- Duff P. Commonly used antibiotics in ObGyn practice. OBG Manag. 2022;34:29, 36-40. doi:10.12788/obgm.0191.
- Centers for Disease Control and Prevention. Treatment information for healthcare professionals: interim clinical guidance for the treatment of monkeypox. Reviewed June 17, 2022. Accessed July 1, 2022. https://www.cdc.gov/poxvirus /monkeypox/clinicians/treatment.html.
- Brincidofovir. Prescribing information. Chimerix, Inc.; 2021. Accessed July 1, 2022. https://www.accessdata.fda.gov /drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf.
- Cidofovir. Package insert. Gilead Sciences, Inc.; 2010. Accessed July 1, 2022. https://www.gilead.com/~/media /Files/pdfs/medicines/other/vistide/vistide.pdf.
- Tecovirimat. Prescribing information. Catalent Pharma Solutions; 2022. Accessed July 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs /label/2022/214518s000lbl.pdf.
- Vaccinia immune globulin IV. Prescribing information. Cangene Corporation; 2010. Accessed July 1, 2022. https: //www.fda.gov/media/77004/download.
- Mbala PK, Huggins JW, Riu-Rovira T, et al. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infect Dis. 2017;216:824-828. doi:10.1093/infdis/jix260.
- Isaacs SN, Shenoy ES. Monkeypox. UpToDate. Updated June 28,2022. Accessed July 1, 2022. https://www.uptodate.com /contents/monkeypox?topicRef=8349&source=see_link
- Graham MB. Monkeypox. Medscape. Updated June 29, 2022. Accessed July 1, 2022. https://emedicine.medscape.com /article/1134714-overview.
- Khalil A, Samara A, O’Brien P, et al. Monkeypox and pregnancy: what do obstetricians need to know? Ultrasound Obstet Gynecol. 2022;60:22-27. doi:10.1002/uog.24968.
- World Health Organization. Monkeypox-United Kingdom of Great Britain and Northern Ireland. May 18, 2022. Accessed July 1, 2022. https://www.who.int/emergencies/diseaseoutbreak-news/item/2022-DON383.
- WHO reports two new monkeypox deaths, cases in new areas. Reuters. July 7, 2022. https://www.reuters.com/world /who-reports-two-new-monkeypox-deaths-2022-07-07/. Accessed July 19, 2022.
- World Health Organization. Multi-country monkeypox outbreak in non-endemic countries: update. May 29, 2022. Accessed July 1, 2022. https://www.who.int /emergencies/disease-outbreak-news/item/2022 -DON388#:~:text=Multi%2Dcountry%20monkeypox%20 outbreak%20in%20non%2Dendemic%20countries%3A%20 Update,-29%20May%202022&text=Since%2013%20 May%202022%2C%20monkeypox,Epidemiological%20 investigations%20are%20ongoing.
- Cono J, Cragan JD, Jamieson DJ, Rasmussen SA. Prophylaxis and treatment of pregnant women for emerging infections andbioterrorism emergencies. Emerg Infect Dis. 2006;12:16311637. doi:10.3201/eid1211.060618.
- Centers for Disease Control and Prevention. Preparation and collection of specimens. Reviewed June 29, 2022. Accessed July 6, 2022. https://www.cdc.gov/poxvirus /monkeypox/clinicians/prep-collection-specimens.html.
- Rao AK, Petersen BW, Whitehill F, et al. Monkeypox vaccination. MMWR Morb Mortal Wkly Rep. 2022;71:734-742. doi:10.15585/mmwr.mm7122e1.
- Smallpox and monkeypox vaccine, live, nonreplicating. Package insert. Bavarian Nordic A/S; 2021. Accessed July 1, 2022. https://www.fda.gov/media/131078/download.
- Duff P. Commonly used antibiotics in ObGyn practice. OBG Manag. 2022;34:29, 36-40. doi:10.12788/obgm.0191.
- Centers for Disease Control and Prevention. Treatment information for healthcare professionals: interim clinical guidance for the treatment of monkeypox. Reviewed June 17, 2022. Accessed July 1, 2022. https://www.cdc.gov/poxvirus /monkeypox/clinicians/treatment.html.
- Brincidofovir. Prescribing information. Chimerix, Inc.; 2021. Accessed July 1, 2022. https://www.accessdata.fda.gov /drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf.
- Cidofovir. Package insert. Gilead Sciences, Inc.; 2010. Accessed July 1, 2022. https://www.gilead.com/~/media /Files/pdfs/medicines/other/vistide/vistide.pdf.
- Tecovirimat. Prescribing information. Catalent Pharma Solutions; 2022. Accessed July 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs /label/2022/214518s000lbl.pdf.
- Vaccinia immune globulin IV. Prescribing information. Cangene Corporation; 2010. Accessed July 1, 2022. https: //www.fda.gov/media/77004/download.
- Mbala PK, Huggins JW, Riu-Rovira T, et al. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infect Dis. 2017;216:824-828. doi:10.1093/infdis/jix260.
Clinicians can help people with severe ME/CFS, even unseen
People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.
Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.
Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.
A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.
Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.
“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.
Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”
Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.
“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.
Misdiagnosis, treatment delays led to life-threatening malnutrition
The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.
“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)
Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”
At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.
“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.
Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”
Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
Caring for the patient with severe or very severe ME/CFS
Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.
In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.
Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.
The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.
Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.
Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.
Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.
The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.
A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.
Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.
Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”
He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.
Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.
A version of this article first appeared on Medscape.com.
People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.
Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.
Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.
A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.
Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.
“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.
Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”
Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.
“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.
Misdiagnosis, treatment delays led to life-threatening malnutrition
The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.
“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)
Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”
At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.
“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.
Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”
Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
Caring for the patient with severe or very severe ME/CFS
Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.
In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.
Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.
The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.
Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.
Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.
Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.
The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.
A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.
Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.
Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”
He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.
Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.
A version of this article first appeared on Medscape.com.
People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.
Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.
Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.
A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.
Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.
“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.
Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”
Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.
“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.
Misdiagnosis, treatment delays led to life-threatening malnutrition
The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.
“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)
Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”
At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.
“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.
Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”
Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
Caring for the patient with severe or very severe ME/CFS
Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.
In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.
Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.
The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.
Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.
Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.
Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.
The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.
A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.
Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.
Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”
He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.
Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.
A version of this article first appeared on Medscape.com.
FROM IACFS/ME 2022
Antibiotic Stewardship Improvement Initiative at a Veterans Health Administration Ambulatory Care Center
The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.1 In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.2 Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.3
The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.
Methods
Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.4 The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.
Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.
Results
From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).
Discussion
The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.
The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.
In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.
The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.
The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.
Limitations
Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.
Conclusions
Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.
Acknowledgments
The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.
1. Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. Appropriate antibiotic use for acute respiratory tract infection in adults: advice for high-value care from the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016;164(6):425-434. doi:10.7326/M15-1840
2. Schroeck JL, Ruh CA, Sellick JA Jr, Ott MC, Mattappallil A, Mergenhagen KA. Factors associated with antibiotic misuse in outpatient treatment for upper respiratory tract infections. Antimicrob Agents Chemother. 2015;59(7):3848-3852. doi:10.1128/AAC.00652-15
3. Francois Watkins LK, Sanchez GV, Albert AP, Roberts RM, Hicks LA. Knowledge and attitudes regarding antibiotic use among adult consumers, adult Hispanic consumers, and health care providers—United States, 2012-2013. MMWR Morb Mortal Wkly Rep. 2015;64(28):767-770. doi:10.15585/mmwr.mm6428a5
4. Centers for Disease Control and Prevention. Antibiotics Aren’t Always the Answer. Accessed June 28, 2022.www.cdc.gov/antibiotic-use/pdfs/AntibioticsArentAlwaystheAnswer-H.pdf
The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.1 In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.2 Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.3
The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.
Methods
Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.4 The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.
Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.
Results
From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).
Discussion
The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.
The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.
In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.
The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.
The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.
Limitations
Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.
Conclusions
Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.
Acknowledgments
The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.
The negative impact of the unnecessary prescribing of antibiotic is well known. Consequences include exposing patients to antibiotic adverse effects, risk of overgrowth of pathogenetic organisms such as clostridial species, unnecessary cost of drugs, and development of selection of antibiotic-resistant organisms in the populace at large. Acute viral respiratory infections are among the leading causes of inappropriate antibiotic usage.1 In a study of 1000 adults with respiratory tract infections in an outpatient setting, 77% of patients were prescribed antibiotics, and the treatment was inappropriate in 64% of those who received prescriptions.2 Patient expectations and clinician perceptions of these expectations play a role. One study showed that 54% of clinicians felt their patients expected to receive antibiotics for a visit due to an acute respiratory infection (ARI), such as a cough or cold; 26% of patients did in fact have this expectation.3
The US Department of Veterans Affairs (VA) Central Ohio Health Care System is a large ambulatory care facility, with 4 associated community-based outpatient clinics, serving more than 43,000 central Ohio veterans and completing more than 500,000 medical appointments annually. An antimicrobial stewardship program has been in place since 2013. In May 2018, the clinical pharmacist assigned to the program alerted medical leadership that, of 67 patients seen in primary care for ARIs between April 16, 2018, and May 15, 2018, 42 (63%) had been prescribed an antibiotic. Based on this finding, clinical leadership designed a process improvement program aimed at reducing inappropriate antibiotic usage for the treatment of uncomplicated ARls likely due to viral pathogens. Key components were clinician and patient education and the substitution of a symptomatic treatment kit in place of an antibiotic prescription.
Methods
Facility clinical leadership, assisted by Volunteer Services, developed a Viral Illness Support Pack to be dispensed by primary care practitioners (PCPs) to patients presenting with symptoms of viral ARIs. The contents of this support pack are shown in the Figure. Patients were provided with tissues, throat lozenges, lip balm, acetaminophen, hand sanitizer, a surgical mask, patient instructions, and the Antibiotics Aren’t Always the Answer pamphlet.4 The contents of the viral support pack were purchased through Volunteer Services using donated funds. In total, 460 packs were distributed to the primary care patient aligned care teams (PACTs), including the community-based outpatient clinics.
Clinicians and care teams received academic detailing prior to distribution of the viral support packs, stressing the importance of avoiding antibiotics to treat viral illnesses. Viral illness support packs were available for distribution from December 1, 2018, through March 31, 2019. The frequency of antibiotic dispensing to patients coded for ARI during this period was compared with that of the same time period in the previous year. All charts were reviewed for coding accuracy. Patients with illnesses requiring antibiotic treatment, such as pneumonia, exacerbations of chronic obstructive pulmonary disease and chronic bronchitis, and streptococcal pharyngitis, were excluded from the study. Statistical significance was determined using the unpaired t test.
Results
From December 1, 2018, to March 31, 2019, 357 viral support packs were distributed to patients (Table). For the historical control period from December 1, 2017, through March 31, 2018, 508 patients were treated for ARIs. Of these, 295 (58%) received clinically inappropriate antibiotics. In contrast, of the 627 patients treated for ARIs during the study period from December 1, 2018, through March 31, 2019, 310 (49%) received clinically inappropriate antibiotics. The 9% decrease during the period when viral support packs were distributed, compared with the prior year, was statistically significant (P = .02).
Discussion
The decrease in antibiotic prescriptions for ARIs was statistically significant. The success of this project can be attributed to 3 factors: clinician education, patient education, and the option for PCPs to provide symptomatic treatment for these patients rather than prescribe an antibiotic.
The importance of antibiotic stewardship has been emphasized to all PCPs at the VA Central Ohio Health Care System. Antibiotic stewardship has been the subject of grand rounds. Prior to distribution of the viral support pack, the chief of specialty medicine, the project’s champion, spoke to all PCPs. Adequate numbers of viral support packs were distributed to all primary care teams.
In addition to direct clinician-to-patient education at the time of the patients’ visits, educational materials were included in the viral support pack. The Antibiotics Aren’t Always the Answer pamphlet is available from the Centers for Disease Control and Prevention. It covers the importance of antibiotic awareness, discusses what antibiotics do and do not treat, how to stay healthy, and causes of antibiotic resistance. The pamphlet contains the clear message that antibiotics are not only ineffective against viral illness, but also can cause significant undesirable outcomes.
The pamphlet Viral Illness Support Pack Traffic Light Card (eAppendix available online at doi:10.12788/fp.0302) provides important clinical information to the patients about their illness. Patients are instructed to contact their primary care team if they are worse after 3 days of illness; symptoms are not improving after 10 days; or they experience blood in respiratory secretions, chills or generalized aching, and localized pain that is one-sided or significantly worsening. Patients are clearly informed to seek further care if not improving with symptomatic treatment.
The ability to provide patients with symptomatic relief, including throat lozenges, lip balm, and acetaminophen, was felt to be important in the success of the project. Furthermore, this eliminated an extra step of the patient needing to visit the pharmacy.
Limitations
Limitations of the study included starting distribution of the support packs somewhat after the onset of the viral illness season, failure to reach all prescribers for academic detailing at the start of the program, and several instances of temporary unavailability of the support packs in some areas.
Conclusions
Patients with ARIs are often significantly symptomatic and frequently believe that they require an antibiotic for treatment. Clinicians may adjust their behavior in response to their patients’ expectations, stated or unstated. The results of this project demonstrate that the combination of patient education and the ready availability of a nonantibiotic symptomatic treatment option can significantly decrease the unnecessary prescribing of antibiotics for viral illnesses.
Acknowledgments
The authors are grateful to Ms. Traci Washington for assistance in sourcing materials; to Karen Corr, PhD, and Anthony Restuccio, MD, for advice on methods; to Mr. Daniel Pignatelli for assistance with data interpretation; and to Mr. Keith Skidmore, Ms. Crystal Conley, and Ms. Megan Harris for assistance with assembling the Viral Illness Support Packs.
1. Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. Appropriate antibiotic use for acute respiratory tract infection in adults: advice for high-value care from the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016;164(6):425-434. doi:10.7326/M15-1840
2. Schroeck JL, Ruh CA, Sellick JA Jr, Ott MC, Mattappallil A, Mergenhagen KA. Factors associated with antibiotic misuse in outpatient treatment for upper respiratory tract infections. Antimicrob Agents Chemother. 2015;59(7):3848-3852. doi:10.1128/AAC.00652-15
3. Francois Watkins LK, Sanchez GV, Albert AP, Roberts RM, Hicks LA. Knowledge and attitudes regarding antibiotic use among adult consumers, adult Hispanic consumers, and health care providers—United States, 2012-2013. MMWR Morb Mortal Wkly Rep. 2015;64(28):767-770. doi:10.15585/mmwr.mm6428a5
4. Centers for Disease Control and Prevention. Antibiotics Aren’t Always the Answer. Accessed June 28, 2022.www.cdc.gov/antibiotic-use/pdfs/AntibioticsArentAlwaystheAnswer-H.pdf
1. Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. Appropriate antibiotic use for acute respiratory tract infection in adults: advice for high-value care from the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016;164(6):425-434. doi:10.7326/M15-1840
2. Schroeck JL, Ruh CA, Sellick JA Jr, Ott MC, Mattappallil A, Mergenhagen KA. Factors associated with antibiotic misuse in outpatient treatment for upper respiratory tract infections. Antimicrob Agents Chemother. 2015;59(7):3848-3852. doi:10.1128/AAC.00652-15
3. Francois Watkins LK, Sanchez GV, Albert AP, Roberts RM, Hicks LA. Knowledge and attitudes regarding antibiotic use among adult consumers, adult Hispanic consumers, and health care providers—United States, 2012-2013. MMWR Morb Mortal Wkly Rep. 2015;64(28):767-770. doi:10.15585/mmwr.mm6428a5
4. Centers for Disease Control and Prevention. Antibiotics Aren’t Always the Answer. Accessed June 28, 2022.www.cdc.gov/antibiotic-use/pdfs/AntibioticsArentAlwaystheAnswer-H.pdf
Postdeployment Respiratory Health: The Roles of the Airborne Hazards and Open Burn Pit Registry and the Post-Deployment Cardiopulmonary Evaluation Network
Case Example
A 37-year-old female never smoker presents to your clinic with progressive dyspnea over the past 15 years. She reports dyspnea on exertion, wheezing, chronic nasal congestion, and difficulty sleeping that started a year after she returned from military deployment to Iraq. She has been unable to exercise, even at low intensity, for the past 5 years, despite being previously active. She has experienced some symptom improvement by taking an albuterol inhaler as needed, loratadine (10 mg), and fluticasone nasal spray (50 mcg). She occasionally uses famotidine for reflux (40 mg). She deployed to Southwest Asia for 12 months (2002-2003) and was primarily stationed in Qayyarah West, an Air Force base in the Mosul district in northern Iraq. She reports exposure during deployment to the fire in the Al-Mishraq sulfur mine, located approximately 25 km north of Qayyarah West, as well as dust storms and burn pits. She currently works as a medical assistant. Her examination is remarkable for normal bronchovesicular breath sounds without any wheezing or crackles on pulmonary evaluation. Her body mass index is 31. You obtain a chest radiograph and spirometry, which are both normal.
The veteran reports feeling frustrated as she has had multiple specialty evaluations in community clinics without receiving a diagnosis, despite worsening symptoms. She reports that she added her information to the Airborne Hazards and Open Burn Pit Registry (AHOBPR). She recently received a letter from the US Department of Veterans Affairs (VA) Post-Deployment Cardiopulmonary Evaluation Network (PDCEN) and is asking you whether she should participate in the PDCEN specialty evaluation. You are not familiar with the military experiences she has described or the programs she asks you about; however, you would like to know more to best care for your patient.
Background
The year 2021 marked the 20th anniversary of the September 11 attacks and the launch of the Global War on Terrorism. Almost 3 million US military personnel have been deployed in support of these operations along with about 300,000 US civilian contractors and thousands of troops from more than 40 nations.1-3
Respiratory hazards associated with deployment to Southwest Asia and Afghanistan are unique and varied. These exposures include blast injuries and a variety of particulate matter sources, such as burn pit combustion byproducts, aeroallergens, and dust storms.7,8,15,16 One air sampling study conducted at 15 deployment sites in Southwest Asia and Afghanistan found mean fine particulate matter (PM2.5) levels were as much as 10 times greater than sampling sites in both rural and urban cities in the United States; all sites sampled exceeded military exposure guidelines (65 µg/m3 for 1 year).17,18 Long-term exposure to PM2.5 has been associated with the development of chronic respiratory and cardiovascular disease; therefore, there has been considerable attention to the respiratory (and nonrespiratory) health of deployed military personnel.19
Concerns regarding the association between deployment and lung disease led to the creation of the national VA Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014 and consists of (1) an online questionnaire to document deployment and medical history, exposure concerns, and symptoms; and (2) an optional in-person or virtual clinical health evaluation at the individual’s local VA medical center or military treatment facility (MTF). As of March 2022, more than 300,000 individuals have completed the online questionnaire of which about 30% declined the optional clinical health evaluation.
The clinical evaluation available to AHOBPR participants has not yet been described in the literature. Therefore, our objectives are to examine AHOBPR clinical evaluation data and review its application throughout the VA. In addition, we will also describe a parallel effort by the VA PDCEN, which is to provide comprehensive multiday clinical evaluations for unique AHOBPR participants with unexplained dyspnea and self-reported respiratory disease. A secondary aim of this publication is to disseminate information to health care professionals (HCPs) within and outside of the VA to aid in the referral and evaluation of previously deployed veterans who experience unexplained dyspnea.
AHOBPR Overview
The AHOBPR is an online questionnaire and optional in-person health evaluation that includes 7 major categories targeting deployment history, symptoms, medical history, health concerns, residential history, nonmilitary occupational history, nonmilitary environmental exposures, and health care utilization. The VA Defense Information Repository is used to obtain service dates for the service member/veteran, conflict involvement, and primary location during deployment. The questionnaire portion of the AHOBPR is administered online. It currently is open to all veterans who served in the Southwest Asia theater of operations (including Iraq, Kuwait, and Egypt) any time after August 2, 1990, or Afghanistan, Djibouti, Syria, or Uzbekistan after September 11, 2001. Veterans are eligible for completing the AHOBPR and optional health evaluation at no cost to the veteran regardless of VA benefits or whether they are currently enrolled in VA health care. Though the focus of the present manuscript is to profile a VA program, it is important to note that the US Department of Defense (DoD) is an active partner with the VA in the promotion of the AHOBPR to service members and similarly provides health evaluations for active-duty service members (including activating Reserve and Guard) through their local MTF.
We reviewed and analyzed AHOBPR operations and VA data from 2014 to 2020. Our analyses were limited to veterans seeking evaluation as well as their corresponding symptoms and HCP’s clinical impression from the electronic health record. As of September 20, 2021, 267,125 individuals completed the AHOBPR. The mean age was 43 years (range, 19-84), and the majority were male (86%) and served in the Army (58%). Open-air burn pits (91%), engine maintenance (38.8%), and convoy operations (71.7%) were the most common deployment-related exposures.
The optional in-person AHOBPR health evaluation may be requested by the veteran after completing the online questionnaire and is performed at the veteran’s local VA facility. The evaluation is most often completed by an environmental health clinician or primary care practitioner (PCP). A variety of resources are available to providers for training on this topic, including fact sheets, webinars, monthly calls, conferences, and accredited e-learning.20 As part of the clinical evaluation, the veteran’s chief concerns are assessed and evaluated. At the time of our analysis, 24,578 clinical examinations were performed across 126 VA medical facilities, with considerable geographic variation. Veterans receiving evaluations were predominantly male (89%) with a median age of 46.0 years (IQR, 15). Veterans’ major respiratory concerns included dyspnea (45.1%), decreased exercise ability (34.8%), and cough > 3 weeks (30.3%) (Table). After clinical evaluation by a VA or MTF HCP, 47.8% were found to have a respiratory diagnosis, including asthma (30.1%), COPD (12.8%), and bronchitis (11.9%).
Registry participants who opt to receive the clinical evaluation may benefit directly by undergoing a detailed clinical history and physical examination as well as having the opportunity to document their health concerns. For some, clinicians may need to refer veterans for additional specialty testing beyond this standard AHOBPR clinical evaluation. Although these evaluations can help address some of the veterans’ concerns, a substantial number may have unexplained respiratory symptoms that warrant further investigation.
Post-Deployment Cardiopulmonary Evaluation Network Clinical Evaluation
In May 2019, the VA established the Airborne Hazards and Burn Pits Center of Excellence (AHBPCE). One of the AHBPCE’s objectives is to deliver specialized care and consultation for veterans with concerns about their postdeployment health, including, but not limited to, unexplained dyspnea. To meet this objective, the AHBPCE developed the PDCEN, a national network consisting of specialty HCPs from 5 VA medical centers—located in San Francisco, California; Denver, Colorado; Baltimore, Maryland; Ann Arbor, Michigan; and East Orange, New Jersey. Collectively, the PDCEN has developed a standardized approach for the comprehensive clinical evaluation of unexplained dyspnea that is implemented uniformly across sites. Staff at the PDCEN screen the AHOBPR to identify veterans with features of respiratory disease and invite them to participate in an in-person evaluation at the nearest PDCEN site. Given the specialty expertise (detailed below) within the Network, the PDCEN focuses on complex cases that are resource intensive. To address complex cases of unexplained dyspnea, the PDCEN has developed a core clinical evaluation approach (Figure).
The first step in a veteran’s PDCEN evaluation entails a set of detailed questionnaires that request information about the veteran’s current respiratory, sleep, and mental health symptoms and any associated medical diagnoses. Questionnaires also identify potential exposures to military burn pits, sulfur mine and oil field fires, diesel exhaust fumes, dust storms, urban pollution, explosions/blasts, and chemical weapons. In addition, the questionnaires include deployment geographic location, which may inform future estimates of particulate matter exposure.21 Prior VA and non-VA evaluations and testing of their respiratory concerns are obtained for review. Exposure and health records from the DoD are also reviewed when available.
The next step in the PDCEN evaluation comprises comprehensive testing, including complete pulmonary function testing, methacholine challenge, cardiopulmonary exercise testing, forced oscillometry and exhaled nitric oxide testing, paired high-resolution inspiratory and expiratory chest computed tomography (CT) imaging, sinus CT imaging, direct flexible laryngoscopy, echocardiography, polysomnography, and laboratory blood testing. The testing process is managed by local site coordinators and varies by institution based on availability of each testing modality and subspecialist appointments.
Once testing is completed, the veteran is evaluated by a team of HCPs, including physicians from the disciplines of pulmonary medicine, environmental and occupational health, sleep medicine, otolaryngology and speech pathology, and mental health (when appropriate). After the clinical evaluation has been completed, this team of expert HCPs at each site convenes to provide a final summary review visit intended to be a comprehensive assessment of the veteran’s primary health concerns. The 3 primary objectives of this final review are to inform the veteran of (1) what respiratory and related conditions they have; (2) whether the conditions is/are deployment related; and (3) what treatments and/or follow-up care may enhance their current state of health in partnership with their local HCPs. The PDCEN does not provide ongoing management of any conditions identified during the veteran’s evaluation but communicates findings and recommendations to the veteran and their PCP for long-term care.
Discussion
The AHOBPR was established in response to mounting concerns that service members and veterans were experiencing adverse health effects that might be attributable to deployment-related exposures. Nearly half of all patients currently enrolled in the AHOBPR report dyspnea, and about one-third have decreased exercise tolerance and/or cough. Of those who completed the questionnaire and the subsequent in-person and generalized AHOBPR examination, our interim analysis showed that about half were assigned a respiratory diagnosis. Yet for many veterans, their breathing symptoms remained unexplained or did not respond to treatment.
While the AHOBPR and related examinations address the needs of many veterans, others may require more comprehensive examination. The PDCEN attends to the latter by providing more detailed and comprehensive clinical evaluations of veterans with deployment-related respiratory health concerns and seeks to learn from these evaluations by analyzing data obtained from veterans across sites. As such, the PDCEN hopes not only to improve the health of individual veterans, but also create standard practices for both VA and non-VA community evaluation of veterans exposed to respiratory hazards during deployment.
One of the major challenges in the field of postdeployment respiratory health is the lack of clear universal language or case definitions that encompass the veteran’s clinical concerns. In an influential case series published in 2011, 38 (77%) of 49 soldiers with history of airborne hazard exposure and unexplained exercise intolerance were reported to have histopathology consistent with constrictive bronchiolitis on surgical lung biopsy.14 Subsequent publications have described other histopathologic features in deployed military personnel, including granulomatous inflammation, interstitial lung disease, emphysema, and pleuritis.12-14 Reconciling these findings from surgical lung biopsy with the clinical presentation and noninvasive studies has proved difficult. Therefore, several groups of investigators have proposed terms, including postdeployment respiratory syndrome, deployment-related distal lung disease, and Iraq/Afghanistan War lung injury to describe the increased respiratory symptoms and variety of histopathologic and imaging findings in this population.9,12,22 At present, there remains a lack of consensus on terminology and case definitions as well as the role of military environmental exposures in exacerbating and/or causing these conditions. As HCPs, it is important to appreciate and acknowledge that the ambiguity and controversy pertaining to terminology, causation, and service connections are a common source of frustration experienced by veterans, which are increasingly reflected among reports in popular media and lay press.
A second and related challenge in the field of postdeployment respiratory health that contributes to veteran and HCP frustration is that many of the aforementioned abnormalities described on surgical lung biopsy are not readily identifiable on noninvasive tests, including traditional interpretation of pulmonary function tests or chest CT imaging.12-14,22 Thus, underlying conditions could be overlooked and veterans’ concerns and symptoms may be dismissed or misattributed to other comorbid conditions. While surgical lung biopsies may offer diagnostic clarity in identifying lung disease, there are significant procedural risks of surgical and anesthetic complications. Furthermore, a definitive diagnosis does not necessarily guarantee a clear treatment plan. For example, there are no current therapies approved by the US Food and Drug Administration for the treatment of constrictive bronchiolitis.
Research efforts are underway, including within the PDCEN, to evaluate a more sensitive and noninvasive assessment of the small airways that may even reduce or eliminate the need for surgical lung biopsy. In contrast to traditional pulmonary function testing, which is helpful for evaluation of the larger airways, forced oscillation technique can be used noninvasively, using pressure oscillations to evaluate for diseases of the smaller airways and has been used in the veteran population and in those exposed to dust from the World Trade Center disaster.23-25 Multiple breath washout technique provides a lung clearance index that is determined by the number of lung turnovers it takes to clear the lungs of an inert gas (eg, sulfur hexafluoride, nitrogen). Elevated lung clearance index values suggest ventilation heterogeneity and have been shown to be higher among deployed veterans with dyspnea.26,27 Finally, advanced CT analytic techniques may help identify functional small airways disease and are higher in deployed service members with constrictive bronchiolitis on surgical lung biopsy.28 These innovative noninvasive techniques are experimental but promising, especially as part of a broader evaluation of small airways disease.
AHOBPR clinical evaluations represent an initial step to better understand postdeployment health conditions available to all AHOBPR participants. The PDCEN clinical evaluation extends the AHOBPR evaluation by providing specialty care for certain veterans requiring more comprehensive evaluation while systematically collecting and analyzing clinical data to advance the field. The VA is committed to leveraging these data and all available expertise to provide a clear description of the spectrum of disease in this population and improve our ability to diagnose, follow, and treat respiratory health conditions occurring after deployment to Southwest Asia and Afghanistan.
Case Conclusion
The veteran was referred to a PDCEN site and underwent a comprehensive multidisciplinary evaluation. Pulmonary function testing showed lung volumes and vital capacity within the predicted normal range, mild air trapping, and a low diffusion capacity for carbon monoxide. Methacholine challenge testing was normal; however, forced oscillometry suggested small airways obstruction. A high-resolution CT showed air trapping without parenchymal changes. Cardiopulmonary exercise testing demonstrated a peak exercise capacity within the predicted normal range but low breathing reserve. Otolaryngology evaluation including laryngoscopy suggested chronic nonallergic rhinitis.
At the end of the veteran’s evaluation, a summary review reported nonallergic rhinitis and distal airway obstruction consistent with small airways disease. Both were reported as most likely related to deployment given her significant environmental exposures and the temporal relationship with her deployment and symptom onset as well as lack of other identifiable causes. A more precise histopathologic diagnosis could be firmly established with a surgical lung biopsy, but after shared decision making with a PDCEN HCP, the patient declined to undergo this invasive procedure. After you review the summary review and recommendations from the PDCEN group, you start the veteran on intranasal steroids and a combined inhaled corticosteroid/long-acting β agonist inhaler as well as refer the veteran to pulmonary rehabilitation. After several weeks, she reports an improvement in sleep and nasal symptoms but continues to experience residual exercise intolerance.
This case serves as an example of the significant limitations that a previously active and healthy patient can develop after deployment to Southwest Asia and Afghanistan. Encouraging this veteran to complete the AHOBPR allowed her to be considered for a PDCEN evaluation that provided the opportunity to undergo a comprehensive noninvasive evaluation of her chronic dyspnea. In doing so, she obtained 2 important diagnoses and data from her evaluation will help establish best practices for standardized evaluations of respiratory concerns following deployment. Through the AHOBPR and PDCEN, the VA seeks to better understand postdeployment health conditions, their relationship to military and environmental exposures, and how best to diagnose and treat these conditions.
Acknowledgments
This work was supported by the US Department of Veterans Affairs (VA) Airborne Hazards and Burn Pits Center of Excellence (Public Law 115-929). The authors acknowledge support and contributions from Dr. Eric Shuping and leadership at VA’s Health Outcomes Military Exposures office as well as the New Jersey War Related Illness and Injury Study Center. In addition, we thank Erin McRoberts and Rajeev Swarup for their contributions to the Post-Deployment Cardiopulmonary Evaluation Network. Post-Deployment Cardiopulmonary Evaluation Network members:
Mehrdad Arjomandi, Caroline Davis, Michelle DeLuca, Nancy Eager, Courtney A. Eberhardt, Michael J. Falvo, Timothy Foley, Fiona A.S. Graff, Deborah Heaney, Stella E. Hines, Rachel E. Howard, Nisha Jani, Sheena Kamineni, Silpa Krefft, Mary L. Langlois, Helen Lozier, Simran K. Matharu, Anisa Moore, Lydia Patrick-DeLuca, Edward Pickering, Alexander Rabin, Michelle Robertson, Samantha L. Rogers, Aaron H. Schneider, Anand Shah, Anays Sotolongo, Jennifer H. Therkorn, Rebecca I. Toczylowski, Matthew Watson, Alison D. Wilczynski, Ian W. Wilson, Romi A. Yount.
1. Wenger J, O’Connell C, Cottrell L. Examination of recent deployment experience across the services and components. Exam. RAND Corporation; 2018. Accessed June 27, 2022. doi:10.7249/rr1928
2. Torreon BS. U.S. periods of war and dates of recent conflicts, RS21405. Congressional Research Service; 2017. June 5, 2020. Accessed June 27, 2022. https://crsreports.congress.gov/product/details?prodcode=RS21405
3. Dunigan M, Farmer CM, Burns RM, Hawks A, Setodji CM. Out of the shadows: the health and well-being of private contractors working in conflict environments. RAND Corporation; 2013. Accessed June 27, 2022. https://www.rand.org/pubs/research_reports/RR420.html
4. Szema AM, Peters MC, Weissinger KM, Gagliano CA, Chen JJ. New-onset asthma among soldiers serving in Iraq and Afghanistan. Allergy Asthma Proc. 2010;31(5):67-71. doi:10.2500/aap.2010.31.3383
5. Pugh MJ, Jaramillo CA, Leung KW, et al. Increasing prevalence of chronic lung disease in veterans of the wars in Iraq and Afghanistan. Mil Med. 2016;181(5):476-481. doi:10.7205/MILMED-D-15-00035
6. Falvo MJ, Osinubi OY, Sotolongo AM, Helmer DA. Airborne hazards exposure and respiratory health of Iraq and Afghanistan veterans. Epidemiol Rev. 2015;37:116-130. doi:10.1093/epirev/mxu009
7. McAndrew LM, Teichman RF, Osinubi OY, Jasien JV, Quigley KS. Environmental exposure and health of Operation Enduring Freedom/Operation Iraqi Freedom veterans. J Occup Environ Med. 2012;54(6):665-669. doi:10.1097/JOM.0b013e318255ba1b
8. Smith B, Wong CA, Smith TC, Boyko EJ, Gackstetter GD; Margaret A. K. Ryan for the Millennium Cohort Study Team. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study. Am J Epidemiol. 2009;170(11):1433-1442. doi:10.1093/aje/kwp287
9. Szema AM, Salihi W, Savary K, Chen JJ. Respiratory symptoms necessitating spirometry among soldiers with Iraq/Afghanistan war lung injury. J Occup Environ Med. 2011;53(9):961-965. doi:10.1097/JOM.0b013e31822c9f05
10. Committee on the Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan; Institute of Medicine. Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan. The National Academies Press; 2011. Accessed June 27, 2022. doi:10.17226/1320911. National Academies of Sciences, Engineering, and Medicine. Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations. The National Academies Press; 2020. Accessed June 27, 2022. doi:10.17226/25837
12. Krefft SD, Wolff J, Zell-Baran L, et al. Respiratory diseases in post-9/11 military personnel following Southwest Asia deployment. J Occup Environ Med. 2020;62(5):337-343. doi:10.1097/JOM.0000000000001817
13. Gordetsky J, Kim C, Miller RF, Mehrad M. Non-necrotizing granulomatous pneumonitis and chronic pleuritis in soldiers deployed to Southwest Asia. Histopathology. 2020;77(3):453-459. doi:10.1111/his.14135
14. King MS, Eisenberg R, Newman JH, et al. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011;365(3):222-230. doi:10.1056/NEJMoa1101388
15. Helmer DA, Rossignol M, Blatt M, Agarwal R, Teichman R, Lange G. Health and exposure concerns of veterans deployed to Iraq and Afghanistan. J Occup Environ Med. 2007;49(5):475-480. doi:10.1097/JOM.0b013e318042d682
16. Kim YH, Warren SH, Kooter I, et al. Chemistry, lung toxicity and mutagenicity of burn pit smoke-related particulate matter. Part Fibre Toxicol. 2021;18(1):45. Published 2021 Dec 16. doi:10.1186/s12989-021-00435-w
17. Engelbrecht JP, McDonald EV, Gillies JA, Jayanty RK, Casuccio G, Gertler AW. Characterizing mineral dusts and other aerosols from the Middle East—Part 1: ambient sampling. Inhal Toxicol. 2009;21(4):297-326. doi:10.1080/08958370802464273
18. US Army Public Health Command. Technical guide 230: environmental health risk assessment and chemical exposure guidelines for deployed military personnel, 2013 revision. Accessed June 27, 2022. https://phc.amedd.army.mil/PHC%20Resource%20Library/TG230-DeploymentEHRA-and-MEGs-2013-Revision.pdf
19. Anderson JO, Thundiyil JG, Stolbach A. Clearing the air: a review of the effects of particulate matter air pollution on human health. J Med Toxicol. 2012;8(2):166-175. doi:10.1007/s13181-011-0203-1
20. Shuping E, Schneiderman A. Resources on environmental exposures for military veterans. Am Fam Physician. 2020;101(12):709-710.
21. Masri S, Garshick E, Coull BA, Koutrakis P. A novel calibration approach using satellite and visibility observations to estimate fine particulate matter exposures in Southwest Asia and Afghanistan. J Air Waste Manag Assoc. 2017;67(1):86-95. doi:10.1080/10962247.2016.1230079
22. Gutor SS, Richmond BW, Du RH, et al. Postdeployment respiratory syndrome in soldiers with chronic exertional dyspnea. Am J Surg Pathol. 2021;45(12):1587-1596. doi:10.1097/PAS.0000000000001757
23. Goldman MD, Saadeh C, Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir Physiol Neurobiol. 2005;148(1-2):179-194. doi:10.1016/j.resp.2005.05.026
24. Butzko RP, Sotolongo AM, Helmer DA, et al. Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms. Respir Physiol Neurobiol. 2019;260:8-16. doi:10.1016/j.resp.2018.11.012
25. Oppenheimer BW, Goldring RM, Herberg ME, et al. Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure. Chest. 2007;132(4):1275-1282. doi:10.1378/chest.07-0913
26. Zell-Baran LM, Krefft SD, Moore CM, Wolff J, Meehan R, Rose CS. Multiple breath washout: a noninvasive tool for identifying lung disease in symptomatic military deployers. Respir Med. 2021;176:106281. doi:10.1016/j.rmed.2020.106281
27. Krefft SD, Strand M, Smith J, Stroup C, Meehan R, Rose C. Utility of lung clearance index testing as a noninvasive marker of deployment-related lung disease. J Occup Environ Med. 2017;59(8):707-711. doi:10.1097/JOM.000000000000105828. Davis CW, Lopez CL, Bell AJ, et al. The severity of functional small airways disease in military personnel with constrictive bronchiolitis as measured by quantitative CT [published online ahead of print, 2022 May 24]. Am J Respir Crit Care Med. 2022;10.1164/rccm.202201-0153LE. doi:10.1164/rccm.202201-0153LE
Case Example
A 37-year-old female never smoker presents to your clinic with progressive dyspnea over the past 15 years. She reports dyspnea on exertion, wheezing, chronic nasal congestion, and difficulty sleeping that started a year after she returned from military deployment to Iraq. She has been unable to exercise, even at low intensity, for the past 5 years, despite being previously active. She has experienced some symptom improvement by taking an albuterol inhaler as needed, loratadine (10 mg), and fluticasone nasal spray (50 mcg). She occasionally uses famotidine for reflux (40 mg). She deployed to Southwest Asia for 12 months (2002-2003) and was primarily stationed in Qayyarah West, an Air Force base in the Mosul district in northern Iraq. She reports exposure during deployment to the fire in the Al-Mishraq sulfur mine, located approximately 25 km north of Qayyarah West, as well as dust storms and burn pits. She currently works as a medical assistant. Her examination is remarkable for normal bronchovesicular breath sounds without any wheezing or crackles on pulmonary evaluation. Her body mass index is 31. You obtain a chest radiograph and spirometry, which are both normal.
The veteran reports feeling frustrated as she has had multiple specialty evaluations in community clinics without receiving a diagnosis, despite worsening symptoms. She reports that she added her information to the Airborne Hazards and Open Burn Pit Registry (AHOBPR). She recently received a letter from the US Department of Veterans Affairs (VA) Post-Deployment Cardiopulmonary Evaluation Network (PDCEN) and is asking you whether she should participate in the PDCEN specialty evaluation. You are not familiar with the military experiences she has described or the programs she asks you about; however, you would like to know more to best care for your patient.
Background
The year 2021 marked the 20th anniversary of the September 11 attacks and the launch of the Global War on Terrorism. Almost 3 million US military personnel have been deployed in support of these operations along with about 300,000 US civilian contractors and thousands of troops from more than 40 nations.1-3
Respiratory hazards associated with deployment to Southwest Asia and Afghanistan are unique and varied. These exposures include blast injuries and a variety of particulate matter sources, such as burn pit combustion byproducts, aeroallergens, and dust storms.7,8,15,16 One air sampling study conducted at 15 deployment sites in Southwest Asia and Afghanistan found mean fine particulate matter (PM2.5) levels were as much as 10 times greater than sampling sites in both rural and urban cities in the United States; all sites sampled exceeded military exposure guidelines (65 µg/m3 for 1 year).17,18 Long-term exposure to PM2.5 has been associated with the development of chronic respiratory and cardiovascular disease; therefore, there has been considerable attention to the respiratory (and nonrespiratory) health of deployed military personnel.19
Concerns regarding the association between deployment and lung disease led to the creation of the national VA Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014 and consists of (1) an online questionnaire to document deployment and medical history, exposure concerns, and symptoms; and (2) an optional in-person or virtual clinical health evaluation at the individual’s local VA medical center or military treatment facility (MTF). As of March 2022, more than 300,000 individuals have completed the online questionnaire of which about 30% declined the optional clinical health evaluation.
The clinical evaluation available to AHOBPR participants has not yet been described in the literature. Therefore, our objectives are to examine AHOBPR clinical evaluation data and review its application throughout the VA. In addition, we will also describe a parallel effort by the VA PDCEN, which is to provide comprehensive multiday clinical evaluations for unique AHOBPR participants with unexplained dyspnea and self-reported respiratory disease. A secondary aim of this publication is to disseminate information to health care professionals (HCPs) within and outside of the VA to aid in the referral and evaluation of previously deployed veterans who experience unexplained dyspnea.
AHOBPR Overview
The AHOBPR is an online questionnaire and optional in-person health evaluation that includes 7 major categories targeting deployment history, symptoms, medical history, health concerns, residential history, nonmilitary occupational history, nonmilitary environmental exposures, and health care utilization. The VA Defense Information Repository is used to obtain service dates for the service member/veteran, conflict involvement, and primary location during deployment. The questionnaire portion of the AHOBPR is administered online. It currently is open to all veterans who served in the Southwest Asia theater of operations (including Iraq, Kuwait, and Egypt) any time after August 2, 1990, or Afghanistan, Djibouti, Syria, or Uzbekistan after September 11, 2001. Veterans are eligible for completing the AHOBPR and optional health evaluation at no cost to the veteran regardless of VA benefits or whether they are currently enrolled in VA health care. Though the focus of the present manuscript is to profile a VA program, it is important to note that the US Department of Defense (DoD) is an active partner with the VA in the promotion of the AHOBPR to service members and similarly provides health evaluations for active-duty service members (including activating Reserve and Guard) through their local MTF.
We reviewed and analyzed AHOBPR operations and VA data from 2014 to 2020. Our analyses were limited to veterans seeking evaluation as well as their corresponding symptoms and HCP’s clinical impression from the electronic health record. As of September 20, 2021, 267,125 individuals completed the AHOBPR. The mean age was 43 years (range, 19-84), and the majority were male (86%) and served in the Army (58%). Open-air burn pits (91%), engine maintenance (38.8%), and convoy operations (71.7%) were the most common deployment-related exposures.
The optional in-person AHOBPR health evaluation may be requested by the veteran after completing the online questionnaire and is performed at the veteran’s local VA facility. The evaluation is most often completed by an environmental health clinician or primary care practitioner (PCP). A variety of resources are available to providers for training on this topic, including fact sheets, webinars, monthly calls, conferences, and accredited e-learning.20 As part of the clinical evaluation, the veteran’s chief concerns are assessed and evaluated. At the time of our analysis, 24,578 clinical examinations were performed across 126 VA medical facilities, with considerable geographic variation. Veterans receiving evaluations were predominantly male (89%) with a median age of 46.0 years (IQR, 15). Veterans’ major respiratory concerns included dyspnea (45.1%), decreased exercise ability (34.8%), and cough > 3 weeks (30.3%) (Table). After clinical evaluation by a VA or MTF HCP, 47.8% were found to have a respiratory diagnosis, including asthma (30.1%), COPD (12.8%), and bronchitis (11.9%).
Registry participants who opt to receive the clinical evaluation may benefit directly by undergoing a detailed clinical history and physical examination as well as having the opportunity to document their health concerns. For some, clinicians may need to refer veterans for additional specialty testing beyond this standard AHOBPR clinical evaluation. Although these evaluations can help address some of the veterans’ concerns, a substantial number may have unexplained respiratory symptoms that warrant further investigation.
Post-Deployment Cardiopulmonary Evaluation Network Clinical Evaluation
In May 2019, the VA established the Airborne Hazards and Burn Pits Center of Excellence (AHBPCE). One of the AHBPCE’s objectives is to deliver specialized care and consultation for veterans with concerns about their postdeployment health, including, but not limited to, unexplained dyspnea. To meet this objective, the AHBPCE developed the PDCEN, a national network consisting of specialty HCPs from 5 VA medical centers—located in San Francisco, California; Denver, Colorado; Baltimore, Maryland; Ann Arbor, Michigan; and East Orange, New Jersey. Collectively, the PDCEN has developed a standardized approach for the comprehensive clinical evaluation of unexplained dyspnea that is implemented uniformly across sites. Staff at the PDCEN screen the AHOBPR to identify veterans with features of respiratory disease and invite them to participate in an in-person evaluation at the nearest PDCEN site. Given the specialty expertise (detailed below) within the Network, the PDCEN focuses on complex cases that are resource intensive. To address complex cases of unexplained dyspnea, the PDCEN has developed a core clinical evaluation approach (Figure).
The first step in a veteran’s PDCEN evaluation entails a set of detailed questionnaires that request information about the veteran’s current respiratory, sleep, and mental health symptoms and any associated medical diagnoses. Questionnaires also identify potential exposures to military burn pits, sulfur mine and oil field fires, diesel exhaust fumes, dust storms, urban pollution, explosions/blasts, and chemical weapons. In addition, the questionnaires include deployment geographic location, which may inform future estimates of particulate matter exposure.21 Prior VA and non-VA evaluations and testing of their respiratory concerns are obtained for review. Exposure and health records from the DoD are also reviewed when available.
The next step in the PDCEN evaluation comprises comprehensive testing, including complete pulmonary function testing, methacholine challenge, cardiopulmonary exercise testing, forced oscillometry and exhaled nitric oxide testing, paired high-resolution inspiratory and expiratory chest computed tomography (CT) imaging, sinus CT imaging, direct flexible laryngoscopy, echocardiography, polysomnography, and laboratory blood testing. The testing process is managed by local site coordinators and varies by institution based on availability of each testing modality and subspecialist appointments.
Once testing is completed, the veteran is evaluated by a team of HCPs, including physicians from the disciplines of pulmonary medicine, environmental and occupational health, sleep medicine, otolaryngology and speech pathology, and mental health (when appropriate). After the clinical evaluation has been completed, this team of expert HCPs at each site convenes to provide a final summary review visit intended to be a comprehensive assessment of the veteran’s primary health concerns. The 3 primary objectives of this final review are to inform the veteran of (1) what respiratory and related conditions they have; (2) whether the conditions is/are deployment related; and (3) what treatments and/or follow-up care may enhance their current state of health in partnership with their local HCPs. The PDCEN does not provide ongoing management of any conditions identified during the veteran’s evaluation but communicates findings and recommendations to the veteran and their PCP for long-term care.
Discussion
The AHOBPR was established in response to mounting concerns that service members and veterans were experiencing adverse health effects that might be attributable to deployment-related exposures. Nearly half of all patients currently enrolled in the AHOBPR report dyspnea, and about one-third have decreased exercise tolerance and/or cough. Of those who completed the questionnaire and the subsequent in-person and generalized AHOBPR examination, our interim analysis showed that about half were assigned a respiratory diagnosis. Yet for many veterans, their breathing symptoms remained unexplained or did not respond to treatment.
While the AHOBPR and related examinations address the needs of many veterans, others may require more comprehensive examination. The PDCEN attends to the latter by providing more detailed and comprehensive clinical evaluations of veterans with deployment-related respiratory health concerns and seeks to learn from these evaluations by analyzing data obtained from veterans across sites. As such, the PDCEN hopes not only to improve the health of individual veterans, but also create standard practices for both VA and non-VA community evaluation of veterans exposed to respiratory hazards during deployment.
One of the major challenges in the field of postdeployment respiratory health is the lack of clear universal language or case definitions that encompass the veteran’s clinical concerns. In an influential case series published in 2011, 38 (77%) of 49 soldiers with history of airborne hazard exposure and unexplained exercise intolerance were reported to have histopathology consistent with constrictive bronchiolitis on surgical lung biopsy.14 Subsequent publications have described other histopathologic features in deployed military personnel, including granulomatous inflammation, interstitial lung disease, emphysema, and pleuritis.12-14 Reconciling these findings from surgical lung biopsy with the clinical presentation and noninvasive studies has proved difficult. Therefore, several groups of investigators have proposed terms, including postdeployment respiratory syndrome, deployment-related distal lung disease, and Iraq/Afghanistan War lung injury to describe the increased respiratory symptoms and variety of histopathologic and imaging findings in this population.9,12,22 At present, there remains a lack of consensus on terminology and case definitions as well as the role of military environmental exposures in exacerbating and/or causing these conditions. As HCPs, it is important to appreciate and acknowledge that the ambiguity and controversy pertaining to terminology, causation, and service connections are a common source of frustration experienced by veterans, which are increasingly reflected among reports in popular media and lay press.
A second and related challenge in the field of postdeployment respiratory health that contributes to veteran and HCP frustration is that many of the aforementioned abnormalities described on surgical lung biopsy are not readily identifiable on noninvasive tests, including traditional interpretation of pulmonary function tests or chest CT imaging.12-14,22 Thus, underlying conditions could be overlooked and veterans’ concerns and symptoms may be dismissed or misattributed to other comorbid conditions. While surgical lung biopsies may offer diagnostic clarity in identifying lung disease, there are significant procedural risks of surgical and anesthetic complications. Furthermore, a definitive diagnosis does not necessarily guarantee a clear treatment plan. For example, there are no current therapies approved by the US Food and Drug Administration for the treatment of constrictive bronchiolitis.
Research efforts are underway, including within the PDCEN, to evaluate a more sensitive and noninvasive assessment of the small airways that may even reduce or eliminate the need for surgical lung biopsy. In contrast to traditional pulmonary function testing, which is helpful for evaluation of the larger airways, forced oscillation technique can be used noninvasively, using pressure oscillations to evaluate for diseases of the smaller airways and has been used in the veteran population and in those exposed to dust from the World Trade Center disaster.23-25 Multiple breath washout technique provides a lung clearance index that is determined by the number of lung turnovers it takes to clear the lungs of an inert gas (eg, sulfur hexafluoride, nitrogen). Elevated lung clearance index values suggest ventilation heterogeneity and have been shown to be higher among deployed veterans with dyspnea.26,27 Finally, advanced CT analytic techniques may help identify functional small airways disease and are higher in deployed service members with constrictive bronchiolitis on surgical lung biopsy.28 These innovative noninvasive techniques are experimental but promising, especially as part of a broader evaluation of small airways disease.
AHOBPR clinical evaluations represent an initial step to better understand postdeployment health conditions available to all AHOBPR participants. The PDCEN clinical evaluation extends the AHOBPR evaluation by providing specialty care for certain veterans requiring more comprehensive evaluation while systematically collecting and analyzing clinical data to advance the field. The VA is committed to leveraging these data and all available expertise to provide a clear description of the spectrum of disease in this population and improve our ability to diagnose, follow, and treat respiratory health conditions occurring after deployment to Southwest Asia and Afghanistan.
Case Conclusion
The veteran was referred to a PDCEN site and underwent a comprehensive multidisciplinary evaluation. Pulmonary function testing showed lung volumes and vital capacity within the predicted normal range, mild air trapping, and a low diffusion capacity for carbon monoxide. Methacholine challenge testing was normal; however, forced oscillometry suggested small airways obstruction. A high-resolution CT showed air trapping without parenchymal changes. Cardiopulmonary exercise testing demonstrated a peak exercise capacity within the predicted normal range but low breathing reserve. Otolaryngology evaluation including laryngoscopy suggested chronic nonallergic rhinitis.
At the end of the veteran’s evaluation, a summary review reported nonallergic rhinitis and distal airway obstruction consistent with small airways disease. Both were reported as most likely related to deployment given her significant environmental exposures and the temporal relationship with her deployment and symptom onset as well as lack of other identifiable causes. A more precise histopathologic diagnosis could be firmly established with a surgical lung biopsy, but after shared decision making with a PDCEN HCP, the patient declined to undergo this invasive procedure. After you review the summary review and recommendations from the PDCEN group, you start the veteran on intranasal steroids and a combined inhaled corticosteroid/long-acting β agonist inhaler as well as refer the veteran to pulmonary rehabilitation. After several weeks, she reports an improvement in sleep and nasal symptoms but continues to experience residual exercise intolerance.
This case serves as an example of the significant limitations that a previously active and healthy patient can develop after deployment to Southwest Asia and Afghanistan. Encouraging this veteran to complete the AHOBPR allowed her to be considered for a PDCEN evaluation that provided the opportunity to undergo a comprehensive noninvasive evaluation of her chronic dyspnea. In doing so, she obtained 2 important diagnoses and data from her evaluation will help establish best practices for standardized evaluations of respiratory concerns following deployment. Through the AHOBPR and PDCEN, the VA seeks to better understand postdeployment health conditions, their relationship to military and environmental exposures, and how best to diagnose and treat these conditions.
Acknowledgments
This work was supported by the US Department of Veterans Affairs (VA) Airborne Hazards and Burn Pits Center of Excellence (Public Law 115-929). The authors acknowledge support and contributions from Dr. Eric Shuping and leadership at VA’s Health Outcomes Military Exposures office as well as the New Jersey War Related Illness and Injury Study Center. In addition, we thank Erin McRoberts and Rajeev Swarup for their contributions to the Post-Deployment Cardiopulmonary Evaluation Network. Post-Deployment Cardiopulmonary Evaluation Network members:
Mehrdad Arjomandi, Caroline Davis, Michelle DeLuca, Nancy Eager, Courtney A. Eberhardt, Michael J. Falvo, Timothy Foley, Fiona A.S. Graff, Deborah Heaney, Stella E. Hines, Rachel E. Howard, Nisha Jani, Sheena Kamineni, Silpa Krefft, Mary L. Langlois, Helen Lozier, Simran K. Matharu, Anisa Moore, Lydia Patrick-DeLuca, Edward Pickering, Alexander Rabin, Michelle Robertson, Samantha L. Rogers, Aaron H. Schneider, Anand Shah, Anays Sotolongo, Jennifer H. Therkorn, Rebecca I. Toczylowski, Matthew Watson, Alison D. Wilczynski, Ian W. Wilson, Romi A. Yount.
Case Example
A 37-year-old female never smoker presents to your clinic with progressive dyspnea over the past 15 years. She reports dyspnea on exertion, wheezing, chronic nasal congestion, and difficulty sleeping that started a year after she returned from military deployment to Iraq. She has been unable to exercise, even at low intensity, for the past 5 years, despite being previously active. She has experienced some symptom improvement by taking an albuterol inhaler as needed, loratadine (10 mg), and fluticasone nasal spray (50 mcg). She occasionally uses famotidine for reflux (40 mg). She deployed to Southwest Asia for 12 months (2002-2003) and was primarily stationed in Qayyarah West, an Air Force base in the Mosul district in northern Iraq. She reports exposure during deployment to the fire in the Al-Mishraq sulfur mine, located approximately 25 km north of Qayyarah West, as well as dust storms and burn pits. She currently works as a medical assistant. Her examination is remarkable for normal bronchovesicular breath sounds without any wheezing or crackles on pulmonary evaluation. Her body mass index is 31. You obtain a chest radiograph and spirometry, which are both normal.
The veteran reports feeling frustrated as she has had multiple specialty evaluations in community clinics without receiving a diagnosis, despite worsening symptoms. She reports that she added her information to the Airborne Hazards and Open Burn Pit Registry (AHOBPR). She recently received a letter from the US Department of Veterans Affairs (VA) Post-Deployment Cardiopulmonary Evaluation Network (PDCEN) and is asking you whether she should participate in the PDCEN specialty evaluation. You are not familiar with the military experiences she has described or the programs she asks you about; however, you would like to know more to best care for your patient.
Background
The year 2021 marked the 20th anniversary of the September 11 attacks and the launch of the Global War on Terrorism. Almost 3 million US military personnel have been deployed in support of these operations along with about 300,000 US civilian contractors and thousands of troops from more than 40 nations.1-3
Respiratory hazards associated with deployment to Southwest Asia and Afghanistan are unique and varied. These exposures include blast injuries and a variety of particulate matter sources, such as burn pit combustion byproducts, aeroallergens, and dust storms.7,8,15,16 One air sampling study conducted at 15 deployment sites in Southwest Asia and Afghanistan found mean fine particulate matter (PM2.5) levels were as much as 10 times greater than sampling sites in both rural and urban cities in the United States; all sites sampled exceeded military exposure guidelines (65 µg/m3 for 1 year).17,18 Long-term exposure to PM2.5 has been associated with the development of chronic respiratory and cardiovascular disease; therefore, there has been considerable attention to the respiratory (and nonrespiratory) health of deployed military personnel.19
Concerns regarding the association between deployment and lung disease led to the creation of the national VA Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014 and consists of (1) an online questionnaire to document deployment and medical history, exposure concerns, and symptoms; and (2) an optional in-person or virtual clinical health evaluation at the individual’s local VA medical center or military treatment facility (MTF). As of March 2022, more than 300,000 individuals have completed the online questionnaire of which about 30% declined the optional clinical health evaluation.
The clinical evaluation available to AHOBPR participants has not yet been described in the literature. Therefore, our objectives are to examine AHOBPR clinical evaluation data and review its application throughout the VA. In addition, we will also describe a parallel effort by the VA PDCEN, which is to provide comprehensive multiday clinical evaluations for unique AHOBPR participants with unexplained dyspnea and self-reported respiratory disease. A secondary aim of this publication is to disseminate information to health care professionals (HCPs) within and outside of the VA to aid in the referral and evaluation of previously deployed veterans who experience unexplained dyspnea.
AHOBPR Overview
The AHOBPR is an online questionnaire and optional in-person health evaluation that includes 7 major categories targeting deployment history, symptoms, medical history, health concerns, residential history, nonmilitary occupational history, nonmilitary environmental exposures, and health care utilization. The VA Defense Information Repository is used to obtain service dates for the service member/veteran, conflict involvement, and primary location during deployment. The questionnaire portion of the AHOBPR is administered online. It currently is open to all veterans who served in the Southwest Asia theater of operations (including Iraq, Kuwait, and Egypt) any time after August 2, 1990, or Afghanistan, Djibouti, Syria, or Uzbekistan after September 11, 2001. Veterans are eligible for completing the AHOBPR and optional health evaluation at no cost to the veteran regardless of VA benefits or whether they are currently enrolled in VA health care. Though the focus of the present manuscript is to profile a VA program, it is important to note that the US Department of Defense (DoD) is an active partner with the VA in the promotion of the AHOBPR to service members and similarly provides health evaluations for active-duty service members (including activating Reserve and Guard) through their local MTF.
We reviewed and analyzed AHOBPR operations and VA data from 2014 to 2020. Our analyses were limited to veterans seeking evaluation as well as their corresponding symptoms and HCP’s clinical impression from the electronic health record. As of September 20, 2021, 267,125 individuals completed the AHOBPR. The mean age was 43 years (range, 19-84), and the majority were male (86%) and served in the Army (58%). Open-air burn pits (91%), engine maintenance (38.8%), and convoy operations (71.7%) were the most common deployment-related exposures.
The optional in-person AHOBPR health evaluation may be requested by the veteran after completing the online questionnaire and is performed at the veteran’s local VA facility. The evaluation is most often completed by an environmental health clinician or primary care practitioner (PCP). A variety of resources are available to providers for training on this topic, including fact sheets, webinars, monthly calls, conferences, and accredited e-learning.20 As part of the clinical evaluation, the veteran’s chief concerns are assessed and evaluated. At the time of our analysis, 24,578 clinical examinations were performed across 126 VA medical facilities, with considerable geographic variation. Veterans receiving evaluations were predominantly male (89%) with a median age of 46.0 years (IQR, 15). Veterans’ major respiratory concerns included dyspnea (45.1%), decreased exercise ability (34.8%), and cough > 3 weeks (30.3%) (Table). After clinical evaluation by a VA or MTF HCP, 47.8% were found to have a respiratory diagnosis, including asthma (30.1%), COPD (12.8%), and bronchitis (11.9%).
Registry participants who opt to receive the clinical evaluation may benefit directly by undergoing a detailed clinical history and physical examination as well as having the opportunity to document their health concerns. For some, clinicians may need to refer veterans for additional specialty testing beyond this standard AHOBPR clinical evaluation. Although these evaluations can help address some of the veterans’ concerns, a substantial number may have unexplained respiratory symptoms that warrant further investigation.
Post-Deployment Cardiopulmonary Evaluation Network Clinical Evaluation
In May 2019, the VA established the Airborne Hazards and Burn Pits Center of Excellence (AHBPCE). One of the AHBPCE’s objectives is to deliver specialized care and consultation for veterans with concerns about their postdeployment health, including, but not limited to, unexplained dyspnea. To meet this objective, the AHBPCE developed the PDCEN, a national network consisting of specialty HCPs from 5 VA medical centers—located in San Francisco, California; Denver, Colorado; Baltimore, Maryland; Ann Arbor, Michigan; and East Orange, New Jersey. Collectively, the PDCEN has developed a standardized approach for the comprehensive clinical evaluation of unexplained dyspnea that is implemented uniformly across sites. Staff at the PDCEN screen the AHOBPR to identify veterans with features of respiratory disease and invite them to participate in an in-person evaluation at the nearest PDCEN site. Given the specialty expertise (detailed below) within the Network, the PDCEN focuses on complex cases that are resource intensive. To address complex cases of unexplained dyspnea, the PDCEN has developed a core clinical evaluation approach (Figure).
The first step in a veteran’s PDCEN evaluation entails a set of detailed questionnaires that request information about the veteran’s current respiratory, sleep, and mental health symptoms and any associated medical diagnoses. Questionnaires also identify potential exposures to military burn pits, sulfur mine and oil field fires, diesel exhaust fumes, dust storms, urban pollution, explosions/blasts, and chemical weapons. In addition, the questionnaires include deployment geographic location, which may inform future estimates of particulate matter exposure.21 Prior VA and non-VA evaluations and testing of their respiratory concerns are obtained for review. Exposure and health records from the DoD are also reviewed when available.
The next step in the PDCEN evaluation comprises comprehensive testing, including complete pulmonary function testing, methacholine challenge, cardiopulmonary exercise testing, forced oscillometry and exhaled nitric oxide testing, paired high-resolution inspiratory and expiratory chest computed tomography (CT) imaging, sinus CT imaging, direct flexible laryngoscopy, echocardiography, polysomnography, and laboratory blood testing. The testing process is managed by local site coordinators and varies by institution based on availability of each testing modality and subspecialist appointments.
Once testing is completed, the veteran is evaluated by a team of HCPs, including physicians from the disciplines of pulmonary medicine, environmental and occupational health, sleep medicine, otolaryngology and speech pathology, and mental health (when appropriate). After the clinical evaluation has been completed, this team of expert HCPs at each site convenes to provide a final summary review visit intended to be a comprehensive assessment of the veteran’s primary health concerns. The 3 primary objectives of this final review are to inform the veteran of (1) what respiratory and related conditions they have; (2) whether the conditions is/are deployment related; and (3) what treatments and/or follow-up care may enhance their current state of health in partnership with their local HCPs. The PDCEN does not provide ongoing management of any conditions identified during the veteran’s evaluation but communicates findings and recommendations to the veteran and their PCP for long-term care.
Discussion
The AHOBPR was established in response to mounting concerns that service members and veterans were experiencing adverse health effects that might be attributable to deployment-related exposures. Nearly half of all patients currently enrolled in the AHOBPR report dyspnea, and about one-third have decreased exercise tolerance and/or cough. Of those who completed the questionnaire and the subsequent in-person and generalized AHOBPR examination, our interim analysis showed that about half were assigned a respiratory diagnosis. Yet for many veterans, their breathing symptoms remained unexplained or did not respond to treatment.
While the AHOBPR and related examinations address the needs of many veterans, others may require more comprehensive examination. The PDCEN attends to the latter by providing more detailed and comprehensive clinical evaluations of veterans with deployment-related respiratory health concerns and seeks to learn from these evaluations by analyzing data obtained from veterans across sites. As such, the PDCEN hopes not only to improve the health of individual veterans, but also create standard practices for both VA and non-VA community evaluation of veterans exposed to respiratory hazards during deployment.
One of the major challenges in the field of postdeployment respiratory health is the lack of clear universal language or case definitions that encompass the veteran’s clinical concerns. In an influential case series published in 2011, 38 (77%) of 49 soldiers with history of airborne hazard exposure and unexplained exercise intolerance were reported to have histopathology consistent with constrictive bronchiolitis on surgical lung biopsy.14 Subsequent publications have described other histopathologic features in deployed military personnel, including granulomatous inflammation, interstitial lung disease, emphysema, and pleuritis.12-14 Reconciling these findings from surgical lung biopsy with the clinical presentation and noninvasive studies has proved difficult. Therefore, several groups of investigators have proposed terms, including postdeployment respiratory syndrome, deployment-related distal lung disease, and Iraq/Afghanistan War lung injury to describe the increased respiratory symptoms and variety of histopathologic and imaging findings in this population.9,12,22 At present, there remains a lack of consensus on terminology and case definitions as well as the role of military environmental exposures in exacerbating and/or causing these conditions. As HCPs, it is important to appreciate and acknowledge that the ambiguity and controversy pertaining to terminology, causation, and service connections are a common source of frustration experienced by veterans, which are increasingly reflected among reports in popular media and lay press.
A second and related challenge in the field of postdeployment respiratory health that contributes to veteran and HCP frustration is that many of the aforementioned abnormalities described on surgical lung biopsy are not readily identifiable on noninvasive tests, including traditional interpretation of pulmonary function tests or chest CT imaging.12-14,22 Thus, underlying conditions could be overlooked and veterans’ concerns and symptoms may be dismissed or misattributed to other comorbid conditions. While surgical lung biopsies may offer diagnostic clarity in identifying lung disease, there are significant procedural risks of surgical and anesthetic complications. Furthermore, a definitive diagnosis does not necessarily guarantee a clear treatment plan. For example, there are no current therapies approved by the US Food and Drug Administration for the treatment of constrictive bronchiolitis.
Research efforts are underway, including within the PDCEN, to evaluate a more sensitive and noninvasive assessment of the small airways that may even reduce or eliminate the need for surgical lung biopsy. In contrast to traditional pulmonary function testing, which is helpful for evaluation of the larger airways, forced oscillation technique can be used noninvasively, using pressure oscillations to evaluate for diseases of the smaller airways and has been used in the veteran population and in those exposed to dust from the World Trade Center disaster.23-25 Multiple breath washout technique provides a lung clearance index that is determined by the number of lung turnovers it takes to clear the lungs of an inert gas (eg, sulfur hexafluoride, nitrogen). Elevated lung clearance index values suggest ventilation heterogeneity and have been shown to be higher among deployed veterans with dyspnea.26,27 Finally, advanced CT analytic techniques may help identify functional small airways disease and are higher in deployed service members with constrictive bronchiolitis on surgical lung biopsy.28 These innovative noninvasive techniques are experimental but promising, especially as part of a broader evaluation of small airways disease.
AHOBPR clinical evaluations represent an initial step to better understand postdeployment health conditions available to all AHOBPR participants. The PDCEN clinical evaluation extends the AHOBPR evaluation by providing specialty care for certain veterans requiring more comprehensive evaluation while systematically collecting and analyzing clinical data to advance the field. The VA is committed to leveraging these data and all available expertise to provide a clear description of the spectrum of disease in this population and improve our ability to diagnose, follow, and treat respiratory health conditions occurring after deployment to Southwest Asia and Afghanistan.
Case Conclusion
The veteran was referred to a PDCEN site and underwent a comprehensive multidisciplinary evaluation. Pulmonary function testing showed lung volumes and vital capacity within the predicted normal range, mild air trapping, and a low diffusion capacity for carbon monoxide. Methacholine challenge testing was normal; however, forced oscillometry suggested small airways obstruction. A high-resolution CT showed air trapping without parenchymal changes. Cardiopulmonary exercise testing demonstrated a peak exercise capacity within the predicted normal range but low breathing reserve. Otolaryngology evaluation including laryngoscopy suggested chronic nonallergic rhinitis.
At the end of the veteran’s evaluation, a summary review reported nonallergic rhinitis and distal airway obstruction consistent with small airways disease. Both were reported as most likely related to deployment given her significant environmental exposures and the temporal relationship with her deployment and symptom onset as well as lack of other identifiable causes. A more precise histopathologic diagnosis could be firmly established with a surgical lung biopsy, but after shared decision making with a PDCEN HCP, the patient declined to undergo this invasive procedure. After you review the summary review and recommendations from the PDCEN group, you start the veteran on intranasal steroids and a combined inhaled corticosteroid/long-acting β agonist inhaler as well as refer the veteran to pulmonary rehabilitation. After several weeks, she reports an improvement in sleep and nasal symptoms but continues to experience residual exercise intolerance.
This case serves as an example of the significant limitations that a previously active and healthy patient can develop after deployment to Southwest Asia and Afghanistan. Encouraging this veteran to complete the AHOBPR allowed her to be considered for a PDCEN evaluation that provided the opportunity to undergo a comprehensive noninvasive evaluation of her chronic dyspnea. In doing so, she obtained 2 important diagnoses and data from her evaluation will help establish best practices for standardized evaluations of respiratory concerns following deployment. Through the AHOBPR and PDCEN, the VA seeks to better understand postdeployment health conditions, their relationship to military and environmental exposures, and how best to diagnose and treat these conditions.
Acknowledgments
This work was supported by the US Department of Veterans Affairs (VA) Airborne Hazards and Burn Pits Center of Excellence (Public Law 115-929). The authors acknowledge support and contributions from Dr. Eric Shuping and leadership at VA’s Health Outcomes Military Exposures office as well as the New Jersey War Related Illness and Injury Study Center. In addition, we thank Erin McRoberts and Rajeev Swarup for their contributions to the Post-Deployment Cardiopulmonary Evaluation Network. Post-Deployment Cardiopulmonary Evaluation Network members:
Mehrdad Arjomandi, Caroline Davis, Michelle DeLuca, Nancy Eager, Courtney A. Eberhardt, Michael J. Falvo, Timothy Foley, Fiona A.S. Graff, Deborah Heaney, Stella E. Hines, Rachel E. Howard, Nisha Jani, Sheena Kamineni, Silpa Krefft, Mary L. Langlois, Helen Lozier, Simran K. Matharu, Anisa Moore, Lydia Patrick-DeLuca, Edward Pickering, Alexander Rabin, Michelle Robertson, Samantha L. Rogers, Aaron H. Schneider, Anand Shah, Anays Sotolongo, Jennifer H. Therkorn, Rebecca I. Toczylowski, Matthew Watson, Alison D. Wilczynski, Ian W. Wilson, Romi A. Yount.
1. Wenger J, O’Connell C, Cottrell L. Examination of recent deployment experience across the services and components. Exam. RAND Corporation; 2018. Accessed June 27, 2022. doi:10.7249/rr1928
2. Torreon BS. U.S. periods of war and dates of recent conflicts, RS21405. Congressional Research Service; 2017. June 5, 2020. Accessed June 27, 2022. https://crsreports.congress.gov/product/details?prodcode=RS21405
3. Dunigan M, Farmer CM, Burns RM, Hawks A, Setodji CM. Out of the shadows: the health and well-being of private contractors working in conflict environments. RAND Corporation; 2013. Accessed June 27, 2022. https://www.rand.org/pubs/research_reports/RR420.html
4. Szema AM, Peters MC, Weissinger KM, Gagliano CA, Chen JJ. New-onset asthma among soldiers serving in Iraq and Afghanistan. Allergy Asthma Proc. 2010;31(5):67-71. doi:10.2500/aap.2010.31.3383
5. Pugh MJ, Jaramillo CA, Leung KW, et al. Increasing prevalence of chronic lung disease in veterans of the wars in Iraq and Afghanistan. Mil Med. 2016;181(5):476-481. doi:10.7205/MILMED-D-15-00035
6. Falvo MJ, Osinubi OY, Sotolongo AM, Helmer DA. Airborne hazards exposure and respiratory health of Iraq and Afghanistan veterans. Epidemiol Rev. 2015;37:116-130. doi:10.1093/epirev/mxu009
7. McAndrew LM, Teichman RF, Osinubi OY, Jasien JV, Quigley KS. Environmental exposure and health of Operation Enduring Freedom/Operation Iraqi Freedom veterans. J Occup Environ Med. 2012;54(6):665-669. doi:10.1097/JOM.0b013e318255ba1b
8. Smith B, Wong CA, Smith TC, Boyko EJ, Gackstetter GD; Margaret A. K. Ryan for the Millennium Cohort Study Team. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study. Am J Epidemiol. 2009;170(11):1433-1442. doi:10.1093/aje/kwp287
9. Szema AM, Salihi W, Savary K, Chen JJ. Respiratory symptoms necessitating spirometry among soldiers with Iraq/Afghanistan war lung injury. J Occup Environ Med. 2011;53(9):961-965. doi:10.1097/JOM.0b013e31822c9f05
10. Committee on the Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan; Institute of Medicine. Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan. The National Academies Press; 2011. Accessed June 27, 2022. doi:10.17226/1320911. National Academies of Sciences, Engineering, and Medicine. Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations. The National Academies Press; 2020. Accessed June 27, 2022. doi:10.17226/25837
12. Krefft SD, Wolff J, Zell-Baran L, et al. Respiratory diseases in post-9/11 military personnel following Southwest Asia deployment. J Occup Environ Med. 2020;62(5):337-343. doi:10.1097/JOM.0000000000001817
13. Gordetsky J, Kim C, Miller RF, Mehrad M. Non-necrotizing granulomatous pneumonitis and chronic pleuritis in soldiers deployed to Southwest Asia. Histopathology. 2020;77(3):453-459. doi:10.1111/his.14135
14. King MS, Eisenberg R, Newman JH, et al. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011;365(3):222-230. doi:10.1056/NEJMoa1101388
15. Helmer DA, Rossignol M, Blatt M, Agarwal R, Teichman R, Lange G. Health and exposure concerns of veterans deployed to Iraq and Afghanistan. J Occup Environ Med. 2007;49(5):475-480. doi:10.1097/JOM.0b013e318042d682
16. Kim YH, Warren SH, Kooter I, et al. Chemistry, lung toxicity and mutagenicity of burn pit smoke-related particulate matter. Part Fibre Toxicol. 2021;18(1):45. Published 2021 Dec 16. doi:10.1186/s12989-021-00435-w
17. Engelbrecht JP, McDonald EV, Gillies JA, Jayanty RK, Casuccio G, Gertler AW. Characterizing mineral dusts and other aerosols from the Middle East—Part 1: ambient sampling. Inhal Toxicol. 2009;21(4):297-326. doi:10.1080/08958370802464273
18. US Army Public Health Command. Technical guide 230: environmental health risk assessment and chemical exposure guidelines for deployed military personnel, 2013 revision. Accessed June 27, 2022. https://phc.amedd.army.mil/PHC%20Resource%20Library/TG230-DeploymentEHRA-and-MEGs-2013-Revision.pdf
19. Anderson JO, Thundiyil JG, Stolbach A. Clearing the air: a review of the effects of particulate matter air pollution on human health. J Med Toxicol. 2012;8(2):166-175. doi:10.1007/s13181-011-0203-1
20. Shuping E, Schneiderman A. Resources on environmental exposures for military veterans. Am Fam Physician. 2020;101(12):709-710.
21. Masri S, Garshick E, Coull BA, Koutrakis P. A novel calibration approach using satellite and visibility observations to estimate fine particulate matter exposures in Southwest Asia and Afghanistan. J Air Waste Manag Assoc. 2017;67(1):86-95. doi:10.1080/10962247.2016.1230079
22. Gutor SS, Richmond BW, Du RH, et al. Postdeployment respiratory syndrome in soldiers with chronic exertional dyspnea. Am J Surg Pathol. 2021;45(12):1587-1596. doi:10.1097/PAS.0000000000001757
23. Goldman MD, Saadeh C, Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir Physiol Neurobiol. 2005;148(1-2):179-194. doi:10.1016/j.resp.2005.05.026
24. Butzko RP, Sotolongo AM, Helmer DA, et al. Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms. Respir Physiol Neurobiol. 2019;260:8-16. doi:10.1016/j.resp.2018.11.012
25. Oppenheimer BW, Goldring RM, Herberg ME, et al. Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure. Chest. 2007;132(4):1275-1282. doi:10.1378/chest.07-0913
26. Zell-Baran LM, Krefft SD, Moore CM, Wolff J, Meehan R, Rose CS. Multiple breath washout: a noninvasive tool for identifying lung disease in symptomatic military deployers. Respir Med. 2021;176:106281. doi:10.1016/j.rmed.2020.106281
27. Krefft SD, Strand M, Smith J, Stroup C, Meehan R, Rose C. Utility of lung clearance index testing as a noninvasive marker of deployment-related lung disease. J Occup Environ Med. 2017;59(8):707-711. doi:10.1097/JOM.000000000000105828. Davis CW, Lopez CL, Bell AJ, et al. The severity of functional small airways disease in military personnel with constrictive bronchiolitis as measured by quantitative CT [published online ahead of print, 2022 May 24]. Am J Respir Crit Care Med. 2022;10.1164/rccm.202201-0153LE. doi:10.1164/rccm.202201-0153LE
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2. Torreon BS. U.S. periods of war and dates of recent conflicts, RS21405. Congressional Research Service; 2017. June 5, 2020. Accessed June 27, 2022. https://crsreports.congress.gov/product/details?prodcode=RS21405
3. Dunigan M, Farmer CM, Burns RM, Hawks A, Setodji CM. Out of the shadows: the health and well-being of private contractors working in conflict environments. RAND Corporation; 2013. Accessed June 27, 2022. https://www.rand.org/pubs/research_reports/RR420.html
4. Szema AM, Peters MC, Weissinger KM, Gagliano CA, Chen JJ. New-onset asthma among soldiers serving in Iraq and Afghanistan. Allergy Asthma Proc. 2010;31(5):67-71. doi:10.2500/aap.2010.31.3383
5. Pugh MJ, Jaramillo CA, Leung KW, et al. Increasing prevalence of chronic lung disease in veterans of the wars in Iraq and Afghanistan. Mil Med. 2016;181(5):476-481. doi:10.7205/MILMED-D-15-00035
6. Falvo MJ, Osinubi OY, Sotolongo AM, Helmer DA. Airborne hazards exposure and respiratory health of Iraq and Afghanistan veterans. Epidemiol Rev. 2015;37:116-130. doi:10.1093/epirev/mxu009
7. McAndrew LM, Teichman RF, Osinubi OY, Jasien JV, Quigley KS. Environmental exposure and health of Operation Enduring Freedom/Operation Iraqi Freedom veterans. J Occup Environ Med. 2012;54(6):665-669. doi:10.1097/JOM.0b013e318255ba1b
8. Smith B, Wong CA, Smith TC, Boyko EJ, Gackstetter GD; Margaret A. K. Ryan for the Millennium Cohort Study Team. Newly reported respiratory symptoms and conditions among military personnel deployed to Iraq and Afghanistan: a prospective population-based study. Am J Epidemiol. 2009;170(11):1433-1442. doi:10.1093/aje/kwp287
9. Szema AM, Salihi W, Savary K, Chen JJ. Respiratory symptoms necessitating spirometry among soldiers with Iraq/Afghanistan war lung injury. J Occup Environ Med. 2011;53(9):961-965. doi:10.1097/JOM.0b013e31822c9f05
10. Committee on the Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan; Institute of Medicine. Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan. The National Academies Press; 2011. Accessed June 27, 2022. doi:10.17226/1320911. National Academies of Sciences, Engineering, and Medicine. Respiratory Health Effects of Airborne Hazards Exposures in the Southwest Asia Theater of Military Operations. The National Academies Press; 2020. Accessed June 27, 2022. doi:10.17226/25837
12. Krefft SD, Wolff J, Zell-Baran L, et al. Respiratory diseases in post-9/11 military personnel following Southwest Asia deployment. J Occup Environ Med. 2020;62(5):337-343. doi:10.1097/JOM.0000000000001817
13. Gordetsky J, Kim C, Miller RF, Mehrad M. Non-necrotizing granulomatous pneumonitis and chronic pleuritis in soldiers deployed to Southwest Asia. Histopathology. 2020;77(3):453-459. doi:10.1111/his.14135
14. King MS, Eisenberg R, Newman JH, et al. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011;365(3):222-230. doi:10.1056/NEJMoa1101388
15. Helmer DA, Rossignol M, Blatt M, Agarwal R, Teichman R, Lange G. Health and exposure concerns of veterans deployed to Iraq and Afghanistan. J Occup Environ Med. 2007;49(5):475-480. doi:10.1097/JOM.0b013e318042d682
16. Kim YH, Warren SH, Kooter I, et al. Chemistry, lung toxicity and mutagenicity of burn pit smoke-related particulate matter. Part Fibre Toxicol. 2021;18(1):45. Published 2021 Dec 16. doi:10.1186/s12989-021-00435-w
17. Engelbrecht JP, McDonald EV, Gillies JA, Jayanty RK, Casuccio G, Gertler AW. Characterizing mineral dusts and other aerosols from the Middle East—Part 1: ambient sampling. Inhal Toxicol. 2009;21(4):297-326. doi:10.1080/08958370802464273
18. US Army Public Health Command. Technical guide 230: environmental health risk assessment and chemical exposure guidelines for deployed military personnel, 2013 revision. Accessed June 27, 2022. https://phc.amedd.army.mil/PHC%20Resource%20Library/TG230-DeploymentEHRA-and-MEGs-2013-Revision.pdf
19. Anderson JO, Thundiyil JG, Stolbach A. Clearing the air: a review of the effects of particulate matter air pollution on human health. J Med Toxicol. 2012;8(2):166-175. doi:10.1007/s13181-011-0203-1
20. Shuping E, Schneiderman A. Resources on environmental exposures for military veterans. Am Fam Physician. 2020;101(12):709-710.
21. Masri S, Garshick E, Coull BA, Koutrakis P. A novel calibration approach using satellite and visibility observations to estimate fine particulate matter exposures in Southwest Asia and Afghanistan. J Air Waste Manag Assoc. 2017;67(1):86-95. doi:10.1080/10962247.2016.1230079
22. Gutor SS, Richmond BW, Du RH, et al. Postdeployment respiratory syndrome in soldiers with chronic exertional dyspnea. Am J Surg Pathol. 2021;45(12):1587-1596. doi:10.1097/PAS.0000000000001757
23. Goldman MD, Saadeh C, Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir Physiol Neurobiol. 2005;148(1-2):179-194. doi:10.1016/j.resp.2005.05.026
24. Butzko RP, Sotolongo AM, Helmer DA, et al. Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms. Respir Physiol Neurobiol. 2019;260:8-16. doi:10.1016/j.resp.2018.11.012
25. Oppenheimer BW, Goldring RM, Herberg ME, et al. Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure. Chest. 2007;132(4):1275-1282. doi:10.1378/chest.07-0913
26. Zell-Baran LM, Krefft SD, Moore CM, Wolff J, Meehan R, Rose CS. Multiple breath washout: a noninvasive tool for identifying lung disease in symptomatic military deployers. Respir Med. 2021;176:106281. doi:10.1016/j.rmed.2020.106281
27. Krefft SD, Strand M, Smith J, Stroup C, Meehan R, Rose C. Utility of lung clearance index testing as a noninvasive marker of deployment-related lung disease. J Occup Environ Med. 2017;59(8):707-711. doi:10.1097/JOM.000000000000105828. Davis CW, Lopez CL, Bell AJ, et al. The severity of functional small airways disease in military personnel with constrictive bronchiolitis as measured by quantitative CT [published online ahead of print, 2022 May 24]. Am J Respir Crit Care Med. 2022;10.1164/rccm.202201-0153LE. doi:10.1164/rccm.202201-0153LE