Certain reproductive factors are associated with greater or lower risk of dementia, according to researchers who conducted a large population-based study with UK Biobank data.

Jessica Gong, a PhD candidate at the George Institute for Global Health at University of New South Wales in Australia, and coauthors found a greater dementia risk in women with early and late menarche, women who were younger when they first gave birth, and those who had had a hysterectomy, especially those who had a hysterectomy without concomitant oophorectomy or with a previous oophorectomy.

After controlling for key confounders, the researchers found lower risk of all-cause dementia if women had ever been pregnant, ever had an abortion, had a longer reproductive span, or had later menopause.

Use of oral contraceptive pills was associated with a lower dementia risk, they found.

In this study, there was no evidence that hormone therapy (HT) was associated with dementia risk (hazard ratio, 0.99, 95% confidence interval [0.90-1.09], P =.0828).

The analysis, published online April 5 in PLOS Medicine, comprised 273,240 women and 228,957 men without prevalent dementia.

The authors noted that dementia rates are increasing. Globally, 50 million people live with dementia, and the number is expected to triple by 2050, according to Alzheimer’s Disease International.

“Our study identified certain reproductive factors related to shorter exposure to endogenous estrogen were associated with increased risk of dementia, highlighting the susceptibility in dementia risk pertaining to women,” Ms. Gong told this publication.
 

Risk comparison of men and women

Men were included in this study to compare the association between number of children fathered and the risk of all-cause dementia, with the association in their female counterparts.

The U-shaped associations between the number of children and dementia risk were similar for both sexes, suggesting that the risk difference in women may not be associated with factors associated with childbearing

“It may be more related to social and behavioral factors in parenthood, rather than biological factors involved in childbearing,” Ms. Gong said.

Compared with those with two children, for those without children, the multiple adjusted HR (95% CI) was 1.18 (1.04, 1.33) (P = .027) for women and 1.10 (0.98-1.23) P = .164) for men.

For those with four or more children, the HR was 1.14 (0.98, 1.33) (P = .132) for women and 1.26 (1.10-1.45) (P = .003) for men.

Rachel Buckley, PhD, assistant professor of neurology with a dual appointment at Brigham and Women’s and Massachusetts General hospitals in Boston, told this publication she found the comparison of dementia risk with number of children in men and women “fascinating.”

She said the argument usually is that if women have had more births, then they have had more estrogen through their body because women get a huge injection of hormones in pregnancy.

“The idea is that the more pregnancies you have the more protected you are. But this study put that on its head, because if men and women are showing increased [dementia] risk in the number of children they have, it suggests there must be something about having the children – not necessarily the circulating hormones – that might be having an impact,” Dr. Buckley said.

“I had never thought to compare the number of children in men. I do find that very interesting,” she said.

As for the lack of a link between HT and dementia risk, in this study she said, she wouldn’t shut the door on that discussion just yet.

She noted the long history of controversy in the field about whether there is a protective factor against dementia for estrogen or whether exposure to estrogen leads to increased risk.

Before the landmark Women’s Health Initiative (WHI) study in the 1990s, she pointed out, there was evidence in many observational studies that women who had longer exposure to estrogen – whether that was earlier age at first period and later age at menopause combined or women had taken hormone therapy at some point, had less risk for dementia.

Dr. Buckley said that in a secondary outcome of WHI, however, “there was increased risk for progression to dementia in women who were taking hormone therapy which essentially flipped the field on its ahead because until that point everybody thought that estrogen was a protective factor.”

She said although this study found no association with dementia, she still thinks HT has a role to play and that it may just need to be better tailored to individuals.

“If you think about it, we have our tailored cocktail of hormones in our body and who’s to say that my hormones are going to be the same as yours? Why should you and I be put on the same hormone therapy and assume that will give us the same outcome? I think we could do a lot better with customization and calibration of hormones to aid in women’s health.”
 

Lifetime approach to dementia

Ms. Gong says future dementia risk-reduction strategies should consider sex-specific risk, and consider the reproductive events that took place in women’s lifespans as well as their entire hormone history when assessing dementia risk, to ensure that the strategies are sex sensitive.

Dr. Buckley agrees: “I don’t think we should ever think about dementia in terms of 65 onwards. We know this disease is insidious and it starts very, very early.”

Regarding limitations, the authors noted that it was a retrospective study that included self-reported measures of reproductive factors, which may be inherently subject to recall bias.

A coauthor does consultant work for Amgen, Freeline, and Kirin outside the submitted work. There were no other relevant financial disclosures.

Certain reproductive factors are associated with greater or lower risk of dementia, according to researchers who conducted a large population-based study with UK Biobank data.

Jessica Gong, a PhD candidate at the George Institute for Global Health at University of New South Wales in Australia, and coauthors found a greater dementia risk in women with early and late menarche, women who were younger when they first gave birth, and those who had had a hysterectomy, especially those who had a hysterectomy without concomitant oophorectomy or with a previous oophorectomy.

After controlling for key confounders, the researchers found lower risk of all-cause dementia if women had ever been pregnant, ever had an abortion, had a longer reproductive span, or had later menopause.

Use of oral contraceptive pills was associated with a lower dementia risk, they found.

In this study, there was no evidence that hormone therapy (HT) was associated with dementia risk (hazard ratio, 0.99, 95% confidence interval [0.90-1.09], P =.0828).

The analysis, published online April 5 in PLOS Medicine, comprised 273,240 women and 228,957 men without prevalent dementia.

The authors noted that dementia rates are increasing. Globally, 50 million people live with dementia, and the number is expected to triple by 2050, according to Alzheimer’s Disease International.

“Our study identified certain reproductive factors related to shorter exposure to endogenous estrogen were associated with increased risk of dementia, highlighting the susceptibility in dementia risk pertaining to women,” Ms. Gong told this publication.
 

Risk comparison of men and women

Men were included in this study to compare the association between number of children fathered and the risk of all-cause dementia, with the association in their female counterparts.

The U-shaped associations between the number of children and dementia risk were similar for both sexes, suggesting that the risk difference in women may not be associated with factors associated with childbearing

“It may be more related to social and behavioral factors in parenthood, rather than biological factors involved in childbearing,” Ms. Gong said.

Compared with those with two children, for those without children, the multiple adjusted HR (95% CI) was 1.18 (1.04, 1.33) (P = .027) for women and 1.10 (0.98-1.23) P = .164) for men.

For those with four or more children, the HR was 1.14 (0.98, 1.33) (P = .132) for women and 1.26 (1.10-1.45) (P = .003) for men.

Rachel Buckley, PhD, assistant professor of neurology with a dual appointment at Brigham and Women’s and Massachusetts General hospitals in Boston, told this publication she found the comparison of dementia risk with number of children in men and women “fascinating.”

She said the argument usually is that if women have had more births, then they have had more estrogen through their body because women get a huge injection of hormones in pregnancy.

“The idea is that the more pregnancies you have the more protected you are. But this study put that on its head, because if men and women are showing increased [dementia] risk in the number of children they have, it suggests there must be something about having the children – not necessarily the circulating hormones – that might be having an impact,” Dr. Buckley said.

“I had never thought to compare the number of children in men. I do find that very interesting,” she said.

As for the lack of a link between HT and dementia risk, in this study she said, she wouldn’t shut the door on that discussion just yet.

She noted the long history of controversy in the field about whether there is a protective factor against dementia for estrogen or whether exposure to estrogen leads to increased risk.

Before the landmark Women’s Health Initiative (WHI) study in the 1990s, she pointed out, there was evidence in many observational studies that women who had longer exposure to estrogen – whether that was earlier age at first period and later age at menopause combined or women had taken hormone therapy at some point, had less risk for dementia.

Dr. Buckley said that in a secondary outcome of WHI, however, “there was increased risk for progression to dementia in women who were taking hormone therapy which essentially flipped the field on its ahead because until that point everybody thought that estrogen was a protective factor.”

She said although this study found no association with dementia, she still thinks HT has a role to play and that it may just need to be better tailored to individuals.

“If you think about it, we have our tailored cocktail of hormones in our body and who’s to say that my hormones are going to be the same as yours? Why should you and I be put on the same hormone therapy and assume that will give us the same outcome? I think we could do a lot better with customization and calibration of hormones to aid in women’s health.”
 

Lifetime approach to dementia

Ms. Gong says future dementia risk-reduction strategies should consider sex-specific risk, and consider the reproductive events that took place in women’s lifespans as well as their entire hormone history when assessing dementia risk, to ensure that the strategies are sex sensitive.

Dr. Buckley agrees: “I don’t think we should ever think about dementia in terms of 65 onwards. We know this disease is insidious and it starts very, very early.”

Regarding limitations, the authors noted that it was a retrospective study that included self-reported measures of reproductive factors, which may be inherently subject to recall bias.

A coauthor does consultant work for Amgen, Freeline, and Kirin outside the submitted work. There were no other relevant financial disclosures.

Certain reproductive factors are associated with greater or lower risk of dementia, according to researchers who conducted a large population-based study with UK Biobank data.

Jessica Gong, a PhD candidate at the George Institute for Global Health at University of New South Wales in Australia, and coauthors found a greater dementia risk in women with early and late menarche, women who were younger when they first gave birth, and those who had had a hysterectomy, especially those who had a hysterectomy without concomitant oophorectomy or with a previous oophorectomy.

After controlling for key confounders, the researchers found lower risk of all-cause dementia if women had ever been pregnant, ever had an abortion, had a longer reproductive span, or had later menopause.

Use of oral contraceptive pills was associated with a lower dementia risk, they found.

In this study, there was no evidence that hormone therapy (HT) was associated with dementia risk (hazard ratio, 0.99, 95% confidence interval [0.90-1.09], P =.0828).

The analysis, published online April 5 in PLOS Medicine, comprised 273,240 women and 228,957 men without prevalent dementia.

The authors noted that dementia rates are increasing. Globally, 50 million people live with dementia, and the number is expected to triple by 2050, according to Alzheimer’s Disease International.

“Our study identified certain reproductive factors related to shorter exposure to endogenous estrogen were associated with increased risk of dementia, highlighting the susceptibility in dementia risk pertaining to women,” Ms. Gong told this publication.
 

Risk comparison of men and women

Men were included in this study to compare the association between number of children fathered and the risk of all-cause dementia, with the association in their female counterparts.

The U-shaped associations between the number of children and dementia risk were similar for both sexes, suggesting that the risk difference in women may not be associated with factors associated with childbearing

“It may be more related to social and behavioral factors in parenthood, rather than biological factors involved in childbearing,” Ms. Gong said.

Compared with those with two children, for those without children, the multiple adjusted HR (95% CI) was 1.18 (1.04, 1.33) (P = .027) for women and 1.10 (0.98-1.23) P = .164) for men.

For those with four or more children, the HR was 1.14 (0.98, 1.33) (P = .132) for women and 1.26 (1.10-1.45) (P = .003) for men.

Rachel Buckley, PhD, assistant professor of neurology with a dual appointment at Brigham and Women’s and Massachusetts General hospitals in Boston, told this publication she found the comparison of dementia risk with number of children in men and women “fascinating.”

She said the argument usually is that if women have had more births, then they have had more estrogen through their body because women get a huge injection of hormones in pregnancy.

“The idea is that the more pregnancies you have the more protected you are. But this study put that on its head, because if men and women are showing increased [dementia] risk in the number of children they have, it suggests there must be something about having the children – not necessarily the circulating hormones – that might be having an impact,” Dr. Buckley said.

“I had never thought to compare the number of children in men. I do find that very interesting,” she said.

As for the lack of a link between HT and dementia risk, in this study she said, she wouldn’t shut the door on that discussion just yet.

She noted the long history of controversy in the field about whether there is a protective factor against dementia for estrogen or whether exposure to estrogen leads to increased risk.

Before the landmark Women’s Health Initiative (WHI) study in the 1990s, she pointed out, there was evidence in many observational studies that women who had longer exposure to estrogen – whether that was earlier age at first period and later age at menopause combined or women had taken hormone therapy at some point, had less risk for dementia.

Dr. Buckley said that in a secondary outcome of WHI, however, “there was increased risk for progression to dementia in women who were taking hormone therapy which essentially flipped the field on its ahead because until that point everybody thought that estrogen was a protective factor.”

She said although this study found no association with dementia, she still thinks HT has a role to play and that it may just need to be better tailored to individuals.

“If you think about it, we have our tailored cocktail of hormones in our body and who’s to say that my hormones are going to be the same as yours? Why should you and I be put on the same hormone therapy and assume that will give us the same outcome? I think we could do a lot better with customization and calibration of hormones to aid in women’s health.”
 

Lifetime approach to dementia

Ms. Gong says future dementia risk-reduction strategies should consider sex-specific risk, and consider the reproductive events that took place in women’s lifespans as well as their entire hormone history when assessing dementia risk, to ensure that the strategies are sex sensitive.

Dr. Buckley agrees: “I don’t think we should ever think about dementia in terms of 65 onwards. We know this disease is insidious and it starts very, very early.”

Regarding limitations, the authors noted that it was a retrospective study that included self-reported measures of reproductive factors, which may be inherently subject to recall bias.

A coauthor does consultant work for Amgen, Freeline, and Kirin outside the submitted work. There were no other relevant financial disclosures.

The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.

“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.

Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.

But she was propelled into quite a different role when her mother was admitted to the hospital.

Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.

“She needed someone to translate what was going on because she didn’t feel well,” she added.

Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”

Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”

“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.

The experience prompted Dr. Kunz to share several “communication pearls” via Twitter. Her thread has since garnered thousands of “likes” and scores of comments and retweets.

She began the Twitter thread explaining what prompted her comments:

“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”

“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’

2.  End your patient visit with a summary of the plan for the day.

3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.

4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).

5. Many older [patients] get confused in the hospital. Repetition is a good thing.

6. Speak to a family member at least once per day to relay the plan.

7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’

8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).

9.  When possible, sit at eye level with your patient (I love these stools from @YNHH).

10. Take time to listen.”

Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”

Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”

Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.

“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.

Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”

@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”

Patients also shared experiences and offered suggestions.

“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”

Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”

Dr. Kunz said she was taken aback but pleased by the response to her Tweet.

“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”

Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.

“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”

In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.

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

The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.

“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.

Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.

But she was propelled into quite a different role when her mother was admitted to the hospital.

Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.

“She needed someone to translate what was going on because she didn’t feel well,” she added.

Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”

Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”

“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.

The experience prompted Dr. Kunz to share several “communication pearls” via Twitter. Her thread has since garnered thousands of “likes” and scores of comments and retweets.

She began the Twitter thread explaining what prompted her comments:

“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”

“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’

2.  End your patient visit with a summary of the plan for the day.

3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.

4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).

5. Many older [patients] get confused in the hospital. Repetition is a good thing.

6. Speak to a family member at least once per day to relay the plan.

7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’

8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).

9.  When possible, sit at eye level with your patient (I love these stools from @YNHH).

10. Take time to listen.”

Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”

Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”

Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.

“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.

Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”

@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”

Patients also shared experiences and offered suggestions.

“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”

Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”

Dr. Kunz said she was taken aback but pleased by the response to her Tweet.

“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”

Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.

“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”

In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.

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

The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.

“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.

Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.

But she was propelled into quite a different role when her mother was admitted to the hospital.

Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.

“She needed someone to translate what was going on because she didn’t feel well,” she added.

Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”

Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”

“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.

The experience prompted Dr. Kunz to share several “communication pearls” via Twitter. Her thread has since garnered thousands of “likes” and scores of comments and retweets.

She began the Twitter thread explaining what prompted her comments:

“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”

“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’

2.  End your patient visit with a summary of the plan for the day.

3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.

4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).

5. Many older [patients] get confused in the hospital. Repetition is a good thing.

6. Speak to a family member at least once per day to relay the plan.

7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’

8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).

9.  When possible, sit at eye level with your patient (I love these stools from @YNHH).

10. Take time to listen.”

Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”

Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”

Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.

“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.

Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”

@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”

Patients also shared experiences and offered suggestions.

“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”

Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”

Dr. Kunz said she was taken aback but pleased by the response to her Tweet.

“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”

Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.

“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”

In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.

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

There is a two-lane bridge in my town. It is quaint and picturesque, and when we first moved here, I would gaze out at the water as I drove, letting my mind wander along with the seagulls drifting alongside the car. Until one day, crossing back over, I passed a school bus stopped in the other lane, and instead of waving back, the driver gave me such a fierce look of disapproval I felt like I’d been to the principal’s office. What had I done?

I started paying more attention to the pattern of the other cars on the bridge. Although it appeared to be a standard two-lane width, the lanes weren’t quite wide enough if a school bus or large truck needed to cross at the same time as a car coming from the opposite direction. They had to wait until the other lane was clear. It was an unwritten rule of the town that if you saw a school bus on the other side, you stopped your car and yielded the bridge to the bus. It took me weeks to figure this out. When I did, I felt like I finally belonged in the community. Before, I’d been an outsider.

This got me thinking about culture. Every place has its unwritten rules, whether a community or a workplace. But how do we know the culture of a place? It’s pretty much impossible until we experience it for ourselves.

When I did figure out the bridge, I had a little bit of anger, to be honest. How was I supposed to know about the lanes? There weren’t any signs. Geez.

Now, when I approach the bridge, I don’t even think about it. I know what to do if I see a bus coming.

But sometimes I remember that time of confusion before I deciphered the unwritten rule. I still have a twinge of guilt for having done something wrong, even though it hadn’t been my fault.

It reminded me of a memory from medical training. I was an MS4, and my ER rotation was in a busy county hospital with a level I trauma center. To say that the place was chaotic would be an understatement.

On the first morning, I was shown the chart rack (yes, this was back in the day of paper charts). Charts were placed in the order that patients arrived. Med students and residents were to take a chart in chronological order, go triage and assess the patient, and then find an attending. Once finished, you put the chart back on the rack and picked up the next one. This was the extent of my orientation to the ER.

The days and weeks of the rotation flew by. It was a busy and exciting time. By the end of the month, I’d come to feel a part of the team.

Until one day, after finishing discharging a patient, an attending asked me, “Where’s the billing sheet?”

I had no idea what she was talking about. No one had ever shown me a billing sheet. But by this point, as an MS4, I knew well that if an attending asked you something you didn’t know the answer to, you shouldn’t just say that you didn’t know. You should try to figure out if you could at least approximate an answer first.

As I scrambled in my mind to figure out what she was asking me, she took one look at the apprehension in my eyes and asked again, raising her voice, “You haven’t been doing the billing sheets?”

I thought back to the first day of the rotation. The cursory 30-second orientation. Chart rack. Take one. See the patient. Put it back. See the next patient. Nothing about billing sheets.

“No,” I said. “No one ever told me about – ”

But the attending didn’t care that I hadn’t been instructed on the billing sheets. She ripped into me, yelling about how she couldn’t believe I’d been working there the entire month and was not doing the billing sheets. She showed me what they were and where they were supposed to be going and, in front of the whole staff, treated me like not only the biggest idiot she’d ever worked with but that the hospital had ever seen.

As she berated me, I thought about all the patients I’d seen that month. All the billing sheets I hadn’t placed in the pile. All the attendings who hadn’t gotten credit for the patients they’d staffed with me.

But how could I have known? I wanted to ask. How could I have known if nobody showed me or told me?

It was like the bridge. I was in a new environment and somehow expected to know the rules without anyone telling me; and when I didn’t know, people treated me like I’d done it the wrong way on purpose.

I didn’t end up saying anything more to that attending. What could I have said? She had already unleashed a mountain of her pent-up anger at me.

What I did decide in that moment was that I would never be an attending like that.

Like the bridge, this memory years later can still make me feel guilt and shame for doing something wrong. Even though it wasn’t my fault.

I was thinking about this recently with the Match. Thousands of freshly graduated medical students embarking on their new positions as interns in teaching hospitals across the country.

For anyone who, like me, struggled with the unwritten rules of the medical culture with each new rotation, remember to be kind to yourself. If someone treats you poorly for not knowing something, you are not an idiot. You’ve worked incredibly hard to get where you are, and you deserve to be there.

For attendings and more senior trainees, remember what it was like to be starting in a new place. We all make mistakes, and often it’s simply because of a lack of information.

Trainees shouldn’t have to suffer and be made to feel like outsiders until they figure out the unwritten rules of the place. They belong.
 

Dr. Lycette is medical director of Providence Oncology and Hematology Care Clinic, Seaside, Ore. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

There is a two-lane bridge in my town. It is quaint and picturesque, and when we first moved here, I would gaze out at the water as I drove, letting my mind wander along with the seagulls drifting alongside the car. Until one day, crossing back over, I passed a school bus stopped in the other lane, and instead of waving back, the driver gave me such a fierce look of disapproval I felt like I’d been to the principal’s office. What had I done?

I started paying more attention to the pattern of the other cars on the bridge. Although it appeared to be a standard two-lane width, the lanes weren’t quite wide enough if a school bus or large truck needed to cross at the same time as a car coming from the opposite direction. They had to wait until the other lane was clear. It was an unwritten rule of the town that if you saw a school bus on the other side, you stopped your car and yielded the bridge to the bus. It took me weeks to figure this out. When I did, I felt like I finally belonged in the community. Before, I’d been an outsider.

This got me thinking about culture. Every place has its unwritten rules, whether a community or a workplace. But how do we know the culture of a place? It’s pretty much impossible until we experience it for ourselves.

When I did figure out the bridge, I had a little bit of anger, to be honest. How was I supposed to know about the lanes? There weren’t any signs. Geez.

Now, when I approach the bridge, I don’t even think about it. I know what to do if I see a bus coming.

But sometimes I remember that time of confusion before I deciphered the unwritten rule. I still have a twinge of guilt for having done something wrong, even though it hadn’t been my fault.

It reminded me of a memory from medical training. I was an MS4, and my ER rotation was in a busy county hospital with a level I trauma center. To say that the place was chaotic would be an understatement.

On the first morning, I was shown the chart rack (yes, this was back in the day of paper charts). Charts were placed in the order that patients arrived. Med students and residents were to take a chart in chronological order, go triage and assess the patient, and then find an attending. Once finished, you put the chart back on the rack and picked up the next one. This was the extent of my orientation to the ER.

The days and weeks of the rotation flew by. It was a busy and exciting time. By the end of the month, I’d come to feel a part of the team.

Until one day, after finishing discharging a patient, an attending asked me, “Where’s the billing sheet?”

I had no idea what she was talking about. No one had ever shown me a billing sheet. But by this point, as an MS4, I knew well that if an attending asked you something you didn’t know the answer to, you shouldn’t just say that you didn’t know. You should try to figure out if you could at least approximate an answer first.

As I scrambled in my mind to figure out what she was asking me, she took one look at the apprehension in my eyes and asked again, raising her voice, “You haven’t been doing the billing sheets?”

I thought back to the first day of the rotation. The cursory 30-second orientation. Chart rack. Take one. See the patient. Put it back. See the next patient. Nothing about billing sheets.

“No,” I said. “No one ever told me about – ”

But the attending didn’t care that I hadn’t been instructed on the billing sheets. She ripped into me, yelling about how she couldn’t believe I’d been working there the entire month and was not doing the billing sheets. She showed me what they were and where they were supposed to be going and, in front of the whole staff, treated me like not only the biggest idiot she’d ever worked with but that the hospital had ever seen.

As she berated me, I thought about all the patients I’d seen that month. All the billing sheets I hadn’t placed in the pile. All the attendings who hadn’t gotten credit for the patients they’d staffed with me.

But how could I have known? I wanted to ask. How could I have known if nobody showed me or told me?

It was like the bridge. I was in a new environment and somehow expected to know the rules without anyone telling me; and when I didn’t know, people treated me like I’d done it the wrong way on purpose.

I didn’t end up saying anything more to that attending. What could I have said? She had already unleashed a mountain of her pent-up anger at me.

What I did decide in that moment was that I would never be an attending like that.

Like the bridge, this memory years later can still make me feel guilt and shame for doing something wrong. Even though it wasn’t my fault.

I was thinking about this recently with the Match. Thousands of freshly graduated medical students embarking on their new positions as interns in teaching hospitals across the country.

For anyone who, like me, struggled with the unwritten rules of the medical culture with each new rotation, remember to be kind to yourself. If someone treats you poorly for not knowing something, you are not an idiot. You’ve worked incredibly hard to get where you are, and you deserve to be there.

For attendings and more senior trainees, remember what it was like to be starting in a new place. We all make mistakes, and often it’s simply because of a lack of information.

Trainees shouldn’t have to suffer and be made to feel like outsiders until they figure out the unwritten rules of the place. They belong.
 

Dr. Lycette is medical director of Providence Oncology and Hematology Care Clinic, Seaside, Ore. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

There is a two-lane bridge in my town. It is quaint and picturesque, and when we first moved here, I would gaze out at the water as I drove, letting my mind wander along with the seagulls drifting alongside the car. Until one day, crossing back over, I passed a school bus stopped in the other lane, and instead of waving back, the driver gave me such a fierce look of disapproval I felt like I’d been to the principal’s office. What had I done?

I started paying more attention to the pattern of the other cars on the bridge. Although it appeared to be a standard two-lane width, the lanes weren’t quite wide enough if a school bus or large truck needed to cross at the same time as a car coming from the opposite direction. They had to wait until the other lane was clear. It was an unwritten rule of the town that if you saw a school bus on the other side, you stopped your car and yielded the bridge to the bus. It took me weeks to figure this out. When I did, I felt like I finally belonged in the community. Before, I’d been an outsider.

This got me thinking about culture. Every place has its unwritten rules, whether a community or a workplace. But how do we know the culture of a place? It’s pretty much impossible until we experience it for ourselves.

When I did figure out the bridge, I had a little bit of anger, to be honest. How was I supposed to know about the lanes? There weren’t any signs. Geez.

Now, when I approach the bridge, I don’t even think about it. I know what to do if I see a bus coming.

But sometimes I remember that time of confusion before I deciphered the unwritten rule. I still have a twinge of guilt for having done something wrong, even though it hadn’t been my fault.

It reminded me of a memory from medical training. I was an MS4, and my ER rotation was in a busy county hospital with a level I trauma center. To say that the place was chaotic would be an understatement.

On the first morning, I was shown the chart rack (yes, this was back in the day of paper charts). Charts were placed in the order that patients arrived. Med students and residents were to take a chart in chronological order, go triage and assess the patient, and then find an attending. Once finished, you put the chart back on the rack and picked up the next one. This was the extent of my orientation to the ER.

The days and weeks of the rotation flew by. It was a busy and exciting time. By the end of the month, I’d come to feel a part of the team.

Until one day, after finishing discharging a patient, an attending asked me, “Where’s the billing sheet?”

I had no idea what she was talking about. No one had ever shown me a billing sheet. But by this point, as an MS4, I knew well that if an attending asked you something you didn’t know the answer to, you shouldn’t just say that you didn’t know. You should try to figure out if you could at least approximate an answer first.

As I scrambled in my mind to figure out what she was asking me, she took one look at the apprehension in my eyes and asked again, raising her voice, “You haven’t been doing the billing sheets?”

I thought back to the first day of the rotation. The cursory 30-second orientation. Chart rack. Take one. See the patient. Put it back. See the next patient. Nothing about billing sheets.

“No,” I said. “No one ever told me about – ”

But the attending didn’t care that I hadn’t been instructed on the billing sheets. She ripped into me, yelling about how she couldn’t believe I’d been working there the entire month and was not doing the billing sheets. She showed me what they were and where they were supposed to be going and, in front of the whole staff, treated me like not only the biggest idiot she’d ever worked with but that the hospital had ever seen.

As she berated me, I thought about all the patients I’d seen that month. All the billing sheets I hadn’t placed in the pile. All the attendings who hadn’t gotten credit for the patients they’d staffed with me.

But how could I have known? I wanted to ask. How could I have known if nobody showed me or told me?

It was like the bridge. I was in a new environment and somehow expected to know the rules without anyone telling me; and when I didn’t know, people treated me like I’d done it the wrong way on purpose.

I didn’t end up saying anything more to that attending. What could I have said? She had already unleashed a mountain of her pent-up anger at me.

What I did decide in that moment was that I would never be an attending like that.

Like the bridge, this memory years later can still make me feel guilt and shame for doing something wrong. Even though it wasn’t my fault.

I was thinking about this recently with the Match. Thousands of freshly graduated medical students embarking on their new positions as interns in teaching hospitals across the country.

For anyone who, like me, struggled with the unwritten rules of the medical culture with each new rotation, remember to be kind to yourself. If someone treats you poorly for not knowing something, you are not an idiot. You’ve worked incredibly hard to get where you are, and you deserve to be there.

For attendings and more senior trainees, remember what it was like to be starting in a new place. We all make mistakes, and often it’s simply because of a lack of information.

Trainees shouldn’t have to suffer and be made to feel like outsiders until they figure out the unwritten rules of the place. They belong.
 

Dr. Lycette is medical director of Providence Oncology and Hematology Care Clinic, Seaside, Ore. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

Every day we see stark images of the war in Ukraine – bombed-out buildings, explosions, and bodies lying in the streets. But there’s another, less visible war against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here’s what Ukrainians, and their neighbors, are facing on the infectious disease front.

Andrey Zinchuk, MD, MHS, a pulmonary/critical care physician at Yale and a native of Ukraine who immigrated to the U.S. at the age of 14 with his family, set the background for understanding this crisis. He said that TB and HIV rates in Ukraine have long been especially high, even before the current conflict: “Part of the challenge of the health care system in Ukraine is that it’s difficult to maintain a steady policy because of political instability,” he said. “We’ve had three revolutions in the last 20 years,” not counting the current Russian invasion.

The first was the breakup of the Soviet Union, which led to “an epidemic of people with HIV, hepatitis, and opioid use.” Next was the Orange Revolution in 2004 over fraud during a presidential election. In 2014 came the Maiden Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia.

“That’s when Russia annexed Crimea. There was essentially infiltration in Russian propaganda in the east of the country,” Dr. Zinchuk said. “This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People’s Republics) which were mostly Russian-speaking parts of the country,” an area known as the Donbas. This resulted in a war in eastern Ukraine that began 2014, with more than 10,000 deaths.

After the 2014 revolution, Dr. Zinchuk said, “There was a tremendous change in the way ... medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions.”

Nevertheless, health care expenditures in Ukraine have been quite low. Even before the current conflict, Dr. Zinchuk noted, annual health care expenditures in Ukraine were about $600 per capita. In comparison, it’s about $4,500 per person in Germany and $12,530 in the United States.

Despite those low per-capita expenditures in Ukraine, access to medicines – such as insulin for diabetes and antibiotics for tuberculosis – was stable before the war. But now, Dr. Zinchuk said, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have “no plumbing and have to heat the house by burning firewood.” More significantly, their supply of medicine is unstable.

Asked what infections are of most immediate concern, Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, told this news organization that it was “diarrheal diseases, especially in kids ... The water supply [of Mariupol] is no longer potable, but people are drinking it anyway. And sewage systems are destroyed, and raw sewage is just released into the rivers and streams. So the whole family of diarrheal diseases and war are bedfellows. So are respiratory diseases, whenever we have mass migrations and mixing of ... homeless people and transients.” 

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps. Dr. Vermund added, “The Syrian refugee camps in Lebanon are just tent camps with a million, 2 million people in them ... In theory, what the Poles are doing is a good thing from the point of view of preventing the spread of infection.”

One way of examining infections in war zones is by considering them based on how they are spread.
 

Respiratory infections

Although not as high on the list of concerns as TB or HIV, COVID-19 remains a big problem for infectious disease experts. Last fall, Ukraine ranked just behind the U.S. and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial vaccination series.

The same conditions that fuel TB and COVID – crowding, especially in poorly ventilated settings – could lead to another measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases. Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of TB cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis (MDR-TB) – 27%. Equally disturbing is its ranking as having the second-highest rate of HIV/TB co-infection (26%) even before the war. Experts say war is a perfect breeding ground for TB, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in TB diagnosis and treatment access in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end TB by more than a decade. 

Drug-resistant TB has been one of the biggest worries. In their report on TB in Ukraine, British tuberculosis experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that “drug resistance thrives on fractured health systems and sporadic medicine supply.”

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, “[if] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and patients could become infectious again.

Dr. Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he told this news organization that he’s impressed at the Polish government’s efforts to ensure care. Especially with the triad of HIV, TB, and opioid use, Dr. Wingfield and Dr. Potter emphasized that these problems reflect the social determinants of health – “the experiences and conditions in which people live.” These medical conditions are all quite treatable with support, and once treated they pose no risk to others.
 

HIV and opioid use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world – 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

Dr. Vermund told this news organization that “when Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it’s illegal in Russia to use buprenorphine or methadone ... So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin.”

Dr. Altice added that of 800 patients in the region who had to go cold turkey, “ten percent were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress.”

And as they relapsed, the HIV rate soared. “Fifty percent of the methadone patients have got HIV,” Dr. Altice said, “and if they stop taking the methadone, they’re going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized.”

This experience may soon repeat itself. There were two methadone factories in Ukraine – in Odessa and Kharkiv – that are now shut down by the war. Although there are efforts to import methadone and many other drugs, supply chain issues are “devastating,” Dr. Altice said. “If their medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and they could become infectious again. “[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they’ll be desperate. So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves,” and there will be an explosion in HIV.

Dr. Altice observed that with the immigration to Poland and the west, many Ukrainian refugees “are relying on the kindness of strangers.” They are likely to be “fearful to disclose either their HIV or their TB treatment status,” being afraid of being regarded as modern-day lepers, even though they are likely not infectious. Both Dr. Altice and Dr. Potter emphasized the need for the governments of Poland and other receiving countries to provide the refugees with “reassurance that their health information will not be shared with others.” Dr. Altice emphasized that “this is one of the things that I would say that these other countries have to get right.”

Dr. Potter echoed that, noting that extraordinary care needs to be taken so that shared information is not used for deportation.

When refugees are housed with rural hosts, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with TB, HIV, and addiction who are placed in small, remote locations may have difficulty securing transportation to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, said in an interview that a network of European TB researchers have developed a database on TBNet where patients with TB can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally. Dr. Altice noted that there is an “increased vulnerability beyond the vulnerability that they already [have] just by being a refugee” that we generally don’t recognize. Additionally, Poland and Hungary are not very progressive about methadone therapy nor are those nations well-equipped to provide it.

Dr. Altice explained that even within Ukraine, those who want to move to better their chance of getting their methadone are then at risk of being conscripted. He spoke of the grave calculations men must make, choosing to become internally displaced and risk conscription or losing life-saving methadone or medicines for HIV or TB.

One other unfortunate consequence of war might be a spike in rape, sexual abuse, prostitution, unwanted pregnancies, HIV, and sexually transmitted infections.

There were an estimated 80,100 female sex workers in Ukraine in 2016, with 5.2% HIV positive. In times of war, with no home or income, some women turn to prostitution to survive. Others are victims of sex trafficking, both within Ukraine and as refugees. The Russian invasion increased the risks of a surge in HIV infections, unwanted pregnancies, and abortions. Women who find themselves pregnant due to rape (a common tool of war) or sex trafficking may also struggle to access safe abortions. Poland, for example, has severe restrictions on abortion, and Ukrainian women may turn to unsafe, back-alley abortions, with their resulting high risk of infection.
 

Waterborne infections

Another concern involves waterborne infections. In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern. In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound infections and antimicrobial resistance

The ECDC also reports high rates of antimicrobial resistance (AMR) in Ukraine, particularly involving common gram-negative bacteria, including Escherichia coli (53% resistance to third-generation cephalosporins), Klebsiella pneumoniae (54% resistance to carbapenems), and Acinetobacter spp. (77% resistance to carbapenems). Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for AMR. These AMR often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. WHO has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active anti-vaccine campaign against COVID in Ukraine, while at the same time advocating for vaccines in Russia. According to UNICEF, other countries with relatively low vaccination rates and high vaccine skepticism – Moldova, Romania, and Bulgaria – are at higher risk of polio and measles than those with high vaccination levels.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.

Continuing to try to keep supply chains open within Ukraine and ensuring adequate supplies of medications and vaccines to refugees will also be essential. But, of course, the better solution is to end the war.

Dr. Altice, Dr. Potter, Dr. Wingfield, Dr. Vermund, and Dr. Zinchuk all report no relevant financial relationships.

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

Every day we see stark images of the war in Ukraine – bombed-out buildings, explosions, and bodies lying in the streets. But there’s another, less visible war against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here’s what Ukrainians, and their neighbors, are facing on the infectious disease front.

Andrey Zinchuk, MD, MHS, a pulmonary/critical care physician at Yale and a native of Ukraine who immigrated to the U.S. at the age of 14 with his family, set the background for understanding this crisis. He said that TB and HIV rates in Ukraine have long been especially high, even before the current conflict: “Part of the challenge of the health care system in Ukraine is that it’s difficult to maintain a steady policy because of political instability,” he said. “We’ve had three revolutions in the last 20 years,” not counting the current Russian invasion.

The first was the breakup of the Soviet Union, which led to “an epidemic of people with HIV, hepatitis, and opioid use.” Next was the Orange Revolution in 2004 over fraud during a presidential election. In 2014 came the Maiden Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia.

“That’s when Russia annexed Crimea. There was essentially infiltration in Russian propaganda in the east of the country,” Dr. Zinchuk said. “This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People’s Republics) which were mostly Russian-speaking parts of the country,” an area known as the Donbas. This resulted in a war in eastern Ukraine that began 2014, with more than 10,000 deaths.

After the 2014 revolution, Dr. Zinchuk said, “There was a tremendous change in the way ... medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions.”

Nevertheless, health care expenditures in Ukraine have been quite low. Even before the current conflict, Dr. Zinchuk noted, annual health care expenditures in Ukraine were about $600 per capita. In comparison, it’s about $4,500 per person in Germany and $12,530 in the United States.

Despite those low per-capita expenditures in Ukraine, access to medicines – such as insulin for diabetes and antibiotics for tuberculosis – was stable before the war. But now, Dr. Zinchuk said, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have “no plumbing and have to heat the house by burning firewood.” More significantly, their supply of medicine is unstable.

Asked what infections are of most immediate concern, Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, told this news organization that it was “diarrheal diseases, especially in kids ... The water supply [of Mariupol] is no longer potable, but people are drinking it anyway. And sewage systems are destroyed, and raw sewage is just released into the rivers and streams. So the whole family of diarrheal diseases and war are bedfellows. So are respiratory diseases, whenever we have mass migrations and mixing of ... homeless people and transients.” 

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps. Dr. Vermund added, “The Syrian refugee camps in Lebanon are just tent camps with a million, 2 million people in them ... In theory, what the Poles are doing is a good thing from the point of view of preventing the spread of infection.”

One way of examining infections in war zones is by considering them based on how they are spread.
 

Respiratory infections

Although not as high on the list of concerns as TB or HIV, COVID-19 remains a big problem for infectious disease experts. Last fall, Ukraine ranked just behind the U.S. and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial vaccination series.

The same conditions that fuel TB and COVID – crowding, especially in poorly ventilated settings – could lead to another measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases. Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of TB cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis (MDR-TB) – 27%. Equally disturbing is its ranking as having the second-highest rate of HIV/TB co-infection (26%) even before the war. Experts say war is a perfect breeding ground for TB, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in TB diagnosis and treatment access in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end TB by more than a decade. 

Drug-resistant TB has been one of the biggest worries. In their report on TB in Ukraine, British tuberculosis experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that “drug resistance thrives on fractured health systems and sporadic medicine supply.”

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, “[if] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and patients could become infectious again.

Dr. Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he told this news organization that he’s impressed at the Polish government’s efforts to ensure care. Especially with the triad of HIV, TB, and opioid use, Dr. Wingfield and Dr. Potter emphasized that these problems reflect the social determinants of health – “the experiences and conditions in which people live.” These medical conditions are all quite treatable with support, and once treated they pose no risk to others.
 

HIV and opioid use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world – 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

Dr. Vermund told this news organization that “when Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it’s illegal in Russia to use buprenorphine or methadone ... So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin.”

Dr. Altice added that of 800 patients in the region who had to go cold turkey, “ten percent were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress.”

And as they relapsed, the HIV rate soared. “Fifty percent of the methadone patients have got HIV,” Dr. Altice said, “and if they stop taking the methadone, they’re going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized.”

This experience may soon repeat itself. There were two methadone factories in Ukraine – in Odessa and Kharkiv – that are now shut down by the war. Although there are efforts to import methadone and many other drugs, supply chain issues are “devastating,” Dr. Altice said. “If their medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and they could become infectious again. “[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they’ll be desperate. So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves,” and there will be an explosion in HIV.

Dr. Altice observed that with the immigration to Poland and the west, many Ukrainian refugees “are relying on the kindness of strangers.” They are likely to be “fearful to disclose either their HIV or their TB treatment status,” being afraid of being regarded as modern-day lepers, even though they are likely not infectious. Both Dr. Altice and Dr. Potter emphasized the need for the governments of Poland and other receiving countries to provide the refugees with “reassurance that their health information will not be shared with others.” Dr. Altice emphasized that “this is one of the things that I would say that these other countries have to get right.”

Dr. Potter echoed that, noting that extraordinary care needs to be taken so that shared information is not used for deportation.

When refugees are housed with rural hosts, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with TB, HIV, and addiction who are placed in small, remote locations may have difficulty securing transportation to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, said in an interview that a network of European TB researchers have developed a database on TBNet where patients with TB can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally. Dr. Altice noted that there is an “increased vulnerability beyond the vulnerability that they already [have] just by being a refugee” that we generally don’t recognize. Additionally, Poland and Hungary are not very progressive about methadone therapy nor are those nations well-equipped to provide it.

Dr. Altice explained that even within Ukraine, those who want to move to better their chance of getting their methadone are then at risk of being conscripted. He spoke of the grave calculations men must make, choosing to become internally displaced and risk conscription or losing life-saving methadone or medicines for HIV or TB.

One other unfortunate consequence of war might be a spike in rape, sexual abuse, prostitution, unwanted pregnancies, HIV, and sexually transmitted infections.

There were an estimated 80,100 female sex workers in Ukraine in 2016, with 5.2% HIV positive. In times of war, with no home or income, some women turn to prostitution to survive. Others are victims of sex trafficking, both within Ukraine and as refugees. The Russian invasion increased the risks of a surge in HIV infections, unwanted pregnancies, and abortions. Women who find themselves pregnant due to rape (a common tool of war) or sex trafficking may also struggle to access safe abortions. Poland, for example, has severe restrictions on abortion, and Ukrainian women may turn to unsafe, back-alley abortions, with their resulting high risk of infection.
 

Waterborne infections

Another concern involves waterborne infections. In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern. In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound infections and antimicrobial resistance

The ECDC also reports high rates of antimicrobial resistance (AMR) in Ukraine, particularly involving common gram-negative bacteria, including Escherichia coli (53% resistance to third-generation cephalosporins), Klebsiella pneumoniae (54% resistance to carbapenems), and Acinetobacter spp. (77% resistance to carbapenems). Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for AMR. These AMR often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. WHO has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active anti-vaccine campaign against COVID in Ukraine, while at the same time advocating for vaccines in Russia. According to UNICEF, other countries with relatively low vaccination rates and high vaccine skepticism – Moldova, Romania, and Bulgaria – are at higher risk of polio and measles than those with high vaccination levels.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.

Continuing to try to keep supply chains open within Ukraine and ensuring adequate supplies of medications and vaccines to refugees will also be essential. But, of course, the better solution is to end the war.

Dr. Altice, Dr. Potter, Dr. Wingfield, Dr. Vermund, and Dr. Zinchuk all report no relevant financial relationships.

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

Every day we see stark images of the war in Ukraine – bombed-out buildings, explosions, and bodies lying in the streets. But there’s another, less visible war against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here’s what Ukrainians, and their neighbors, are facing on the infectious disease front.

Andrey Zinchuk, MD, MHS, a pulmonary/critical care physician at Yale and a native of Ukraine who immigrated to the U.S. at the age of 14 with his family, set the background for understanding this crisis. He said that TB and HIV rates in Ukraine have long been especially high, even before the current conflict: “Part of the challenge of the health care system in Ukraine is that it’s difficult to maintain a steady policy because of political instability,” he said. “We’ve had three revolutions in the last 20 years,” not counting the current Russian invasion.

The first was the breakup of the Soviet Union, which led to “an epidemic of people with HIV, hepatitis, and opioid use.” Next was the Orange Revolution in 2004 over fraud during a presidential election. In 2014 came the Maiden Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia.

“That’s when Russia annexed Crimea. There was essentially infiltration in Russian propaganda in the east of the country,” Dr. Zinchuk said. “This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People’s Republics) which were mostly Russian-speaking parts of the country,” an area known as the Donbas. This resulted in a war in eastern Ukraine that began 2014, with more than 10,000 deaths.

After the 2014 revolution, Dr. Zinchuk said, “There was a tremendous change in the way ... medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions.”

Nevertheless, health care expenditures in Ukraine have been quite low. Even before the current conflict, Dr. Zinchuk noted, annual health care expenditures in Ukraine were about $600 per capita. In comparison, it’s about $4,500 per person in Germany and $12,530 in the United States.

Despite those low per-capita expenditures in Ukraine, access to medicines – such as insulin for diabetes and antibiotics for tuberculosis – was stable before the war. But now, Dr. Zinchuk said, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have “no plumbing and have to heat the house by burning firewood.” More significantly, their supply of medicine is unstable.

Asked what infections are of most immediate concern, Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, told this news organization that it was “diarrheal diseases, especially in kids ... The water supply [of Mariupol] is no longer potable, but people are drinking it anyway. And sewage systems are destroyed, and raw sewage is just released into the rivers and streams. So the whole family of diarrheal diseases and war are bedfellows. So are respiratory diseases, whenever we have mass migrations and mixing of ... homeless people and transients.” 

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps. Dr. Vermund added, “The Syrian refugee camps in Lebanon are just tent camps with a million, 2 million people in them ... In theory, what the Poles are doing is a good thing from the point of view of preventing the spread of infection.”

One way of examining infections in war zones is by considering them based on how they are spread.
 

Respiratory infections

Although not as high on the list of concerns as TB or HIV, COVID-19 remains a big problem for infectious disease experts. Last fall, Ukraine ranked just behind the U.S. and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial vaccination series.

The same conditions that fuel TB and COVID – crowding, especially in poorly ventilated settings – could lead to another measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases. Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of TB cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis (MDR-TB) – 27%. Equally disturbing is its ranking as having the second-highest rate of HIV/TB co-infection (26%) even before the war. Experts say war is a perfect breeding ground for TB, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in TB diagnosis and treatment access in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end TB by more than a decade. 

Drug-resistant TB has been one of the biggest worries. In their report on TB in Ukraine, British tuberculosis experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that “drug resistance thrives on fractured health systems and sporadic medicine supply.”

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, “[if] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and patients could become infectious again.

Dr. Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he told this news organization that he’s impressed at the Polish government’s efforts to ensure care. Especially with the triad of HIV, TB, and opioid use, Dr. Wingfield and Dr. Potter emphasized that these problems reflect the social determinants of health – “the experiences and conditions in which people live.” These medical conditions are all quite treatable with support, and once treated they pose no risk to others.
 

HIV and opioid use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world – 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

Dr. Vermund told this news organization that “when Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it’s illegal in Russia to use buprenorphine or methadone ... So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin.”

Dr. Altice added that of 800 patients in the region who had to go cold turkey, “ten percent were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress.”

And as they relapsed, the HIV rate soared. “Fifty percent of the methadone patients have got HIV,” Dr. Altice said, “and if they stop taking the methadone, they’re going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized.”

This experience may soon repeat itself. There were two methadone factories in Ukraine – in Odessa and Kharkiv – that are now shut down by the war. Although there are efforts to import methadone and many other drugs, supply chain issues are “devastating,” Dr. Altice said. “If their medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and they could become infectious again. “[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they’ll be desperate. So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves,” and there will be an explosion in HIV.

Dr. Altice observed that with the immigration to Poland and the west, many Ukrainian refugees “are relying on the kindness of strangers.” They are likely to be “fearful to disclose either their HIV or their TB treatment status,” being afraid of being regarded as modern-day lepers, even though they are likely not infectious. Both Dr. Altice and Dr. Potter emphasized the need for the governments of Poland and other receiving countries to provide the refugees with “reassurance that their health information will not be shared with others.” Dr. Altice emphasized that “this is one of the things that I would say that these other countries have to get right.”

Dr. Potter echoed that, noting that extraordinary care needs to be taken so that shared information is not used for deportation.

When refugees are housed with rural hosts, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with TB, HIV, and addiction who are placed in small, remote locations may have difficulty securing transportation to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, said in an interview that a network of European TB researchers have developed a database on TBNet where patients with TB can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally. Dr. Altice noted that there is an “increased vulnerability beyond the vulnerability that they already [have] just by being a refugee” that we generally don’t recognize. Additionally, Poland and Hungary are not very progressive about methadone therapy nor are those nations well-equipped to provide it.

Dr. Altice explained that even within Ukraine, those who want to move to better their chance of getting their methadone are then at risk of being conscripted. He spoke of the grave calculations men must make, choosing to become internally displaced and risk conscription or losing life-saving methadone or medicines for HIV or TB.

One other unfortunate consequence of war might be a spike in rape, sexual abuse, prostitution, unwanted pregnancies, HIV, and sexually transmitted infections.

There were an estimated 80,100 female sex workers in Ukraine in 2016, with 5.2% HIV positive. In times of war, with no home or income, some women turn to prostitution to survive. Others are victims of sex trafficking, both within Ukraine and as refugees. The Russian invasion increased the risks of a surge in HIV infections, unwanted pregnancies, and abortions. Women who find themselves pregnant due to rape (a common tool of war) or sex trafficking may also struggle to access safe abortions. Poland, for example, has severe restrictions on abortion, and Ukrainian women may turn to unsafe, back-alley abortions, with their resulting high risk of infection.
 

Waterborne infections

Another concern involves waterborne infections. In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern. In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound infections and antimicrobial resistance

The ECDC also reports high rates of antimicrobial resistance (AMR) in Ukraine, particularly involving common gram-negative bacteria, including Escherichia coli (53% resistance to third-generation cephalosporins), Klebsiella pneumoniae (54% resistance to carbapenems), and Acinetobacter spp. (77% resistance to carbapenems). Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for AMR. These AMR often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. WHO has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active anti-vaccine campaign against COVID in Ukraine, while at the same time advocating for vaccines in Russia. According to UNICEF, other countries with relatively low vaccination rates and high vaccine skepticism – Moldova, Romania, and Bulgaria – are at higher risk of polio and measles than those with high vaccination levels.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.

Continuing to try to keep supply chains open within Ukraine and ensuring adequate supplies of medications and vaccines to refugees will also be essential. But, of course, the better solution is to end the war.

Dr. Altice, Dr. Potter, Dr. Wingfield, Dr. Vermund, and Dr. Zinchuk all report no relevant financial relationships.

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

Insomnia rates continue to rise in the setting of the pandemic,¹ contributing to increasing rates of depression and anxiety, as well as worsening symptoms of other severe mental illnesses. Data suggests this symptom, defined as chronic sleep onset and/or sleep continuity problems associated with impaired daytime functioning, is common in psychiatric illnesses, and can worsen their course.²

The incidence of psychiatric illness in patients with insomnia is estimated at near 50%, with the highest rates found in mood disorders such as depression and bipolar disorder, as well as anxiety disorders.³ In patients with diagnosed major depressive disorder, insomnia rates can approach 90%.^4-6

Courtesy Dr. Jennifer Reid

Insomnia has been identified as a risk factor for development of mental illness, including doubling the risk of major depressive disorder and tripling the risk of any depressive or anxiety disorder.^7,8 It can also significantly increase the risk of alcohol abuse and psychosis.⁸

Sleep disturbances can worsen symptoms of diagnosed mental illness, including substance abuse, mood and psychotic disorders.^9-10 In one study, nearly 75% of patients with a diagnosis of schizophrenia or bipolar spectrum disorder had at least one type of sleep disturbance (insomnia, hypersomnia, or delayed sleep phase).¹⁰ This was almost twice the rate in healthy controls. Importantly, compared with well-rested subjects with mental illness in this study, sleep-disordered participants had higher rates of negative and depressive symptoms on the Positive and Negative Syndrome Scale, as well as significantly lower function via the global assessment of functioning.^11,12

Additional data suggests simply being awake during the night (00:00-05:59) elevates risk of suicide. The mean incident rate of completed suicide in one study was a striking four times the rate noted during daytime hours (06:00-23:59 ) (P < .001).¹³

Although insomnia symptoms can resolve after relief from a particular life stressor, as many as half of patients with more severe symptoms develop a chronic course.¹⁴ This then leads to an extended use of many types of sedative-hypnotics designed and studied primarily for short-term use.¹⁵ In a survey reviewing national use of prescription drugs for insomnia, as many as 20% of individuals use a medication to target insomnia in a given month.¹⁶

Fortunately, despite the many challenges posed by COVID-19, particularly for those with psychiatric illness and limited access to care, telehealth has become more readily available. Additionally, digital versions of evidence-based treatments specifically for sleep problems, such as cognitive-behavioral therapy for insomnia (CBT-I), are regularly being developed.

The benefits of CBT-I have been demonstrated repeatedly and it is recommended as the first line treatment for insomnia by the Clinical Guidelines of the American Academy of Sleep Medicine, the Centers for Disease Control and Prevention, and the National Institutes of Health.^17-21 Studies suggest benefits persist long-term, even after completing the therapy sessions, which differ in durability from medication choices.¹⁸

One group that may be particularly suited for treatment with CBT-I is women with insomnia during pregnancy or the postpartum period. In these women, options for treatment may be limited by risk of medication during breastfeeding, as well as difficulty traveling to a physician’s or therapist’s office to receive psychotherapy. However, two recent studies evaluated the use of digital CBT-I to treat insomnia during pregnancy and in the postpartum period, respectively.^22-23

In both studies,the same group of women with insomnia diagnosed during pregnancy were given six weekly 20-minute sessions of digital CBT-I or standard treatment for insomnia, including medication and psychotherapy per their usual provider.

By study end, the pregnant women receiving the CBT-I intervention not only had significantly improved severity of insomnia, they also experienced improved depression and anxiety symptoms, and a decrease in the use of prescription or over-the-counter sleep aides, compared with the standard treatment group, lowering the fetal exposure to medication during pregnancy.²²

In the more recent study, the same group was followed for 6 months post partum.²³ Results were again notable, with the women who received CBT-I reporting significantly less insomnia, as well as significantly lower rates of probable major depression at 3 and 6 months (18% vs. 4%, 10% vs. 0%, respectively.) They also exhibited lower rates of moderate to severe anxiety (17% vs. 4%) at 3 months, compared with those receiving standard care. With as many as one in seven women suffering from postpartum depression, these findings represent a substantial public health benefit.

In summary, insomnia is a critical area of focus for any provider diagnosing and treating psychiatric illness. Attempts to optimize sleep, whether through CBT-I or other psychotherapy approaches, or evidence-based medications dosed for appropriate lengths and at safe doses, should be a part of most, if not all, clinical encounters.

Dr. Reid is a board-certified psychiatrist and award-winning medical educator with a private practice in Philadelphia, as well as a clinical faculty role at the University of Pennsylvania, also in Philadelphia. She attended medical school at Columbia University, New York, and completed her psychiatry residency at the University of California, Los Angeles. Dr. Reid is a regular contributor to Psychology Today with her blog, “Think Like a Shrink,” and writes and podcasts as The Reflective Doc.

References

1. Voitsidis P et al. Psychiatry Res. 2020 Jul;289:113076. doi: 10.1016/j.psychres.2020.113076.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va.: American Psychiatric Publishing, 2013.

3. Ford DE and Kamerow DB. JAMA. 1989;262(11):1479-84. doi: 10.1001/jama.1989.03430110069030.

4. Ohayon MM and Roth T. J Psychiatr Res. Jan-Feb 2003;37(1):9-15. doi: 10.1016/s0022-3956(02)00052-3.

5. Seow LSE et al. J Ment Health. 2016 Dec;25(6):492-9. doi: 10.3109/09638237.2015.1124390.

6. Thase ME. J Clin Psychiatry. 1999;60 Suppl 17:28-31; discussion 46-8.

7. Baglioni C et al. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011.

8. Hertenstein E et al. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006.

9. Brower KJ et al. Medical Hypotheses. 2010;74(5):928-33. doi: 10.1016/j.mehy.2009.10.020.

10. Laskemoen JF et al. Compr Psychiatry. 2019 May;91:6-12. doi: 10.1016/j.comppsych.2019.02.006.

11. Kay SR et al. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

12. Hall R. Psychosomatics. May-Jun 1995;36(3):267-75. doi: 10.1016/S0033-3182(95)71666-8.

13. Perlis ML et al. J Clin Psychiatry. 2016 Jun;77(6):e726-33. doi: 10.4088/JCP.15m10131.

14. Morin CM et al. Arch Intern Med. 2009 Mar 9. doi: 10.1001/archinternmed.2008.610.

15. Cheung J et al. Sleep Med Clin. 2019 Jun;14(2):253-65. doi: 10.1016/j.jsmc.2019.01.006.

16. Bertisch SM et al. Sleep. 2014 Feb 1. doi: 10.5665/sleep.3410.

17. Okajima I et al. Sleep Biol Rhythms. 2010 Nov 28. doi: 10.1111/j.1479-8425.2010.00481.x.

18. Trauer JM et al. Ann Intern Med. 2015 Aug 4. doi: 10.7326/M14-2841.

19. Edinger J et al. J Clin Sleep Med. 2021 Feb 1. doi: 10.5664/jcsm.8986.

20. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/sleep/for-clinicians.html.

21. National Institutes of Health. Sleep Health. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/sleep-health.

22. Felder JN et al. JAMA Psychiatry. 2020;77(5):484-92. doi:10.1001/jamapsychiatry.2019.4491.

23. Felder JN et al. Sleep. 2022 Feb 14. doi: 10.1093/sleep/zsab280.

Insomnia rates continue to rise in the setting of the pandemic,¹ contributing to increasing rates of depression and anxiety, as well as worsening symptoms of other severe mental illnesses. Data suggests this symptom, defined as chronic sleep onset and/or sleep continuity problems associated with impaired daytime functioning, is common in psychiatric illnesses, and can worsen their course.²

The incidence of psychiatric illness in patients with insomnia is estimated at near 50%, with the highest rates found in mood disorders such as depression and bipolar disorder, as well as anxiety disorders.³ In patients with diagnosed major depressive disorder, insomnia rates can approach 90%.^4-6

Courtesy Dr. Jennifer Reid

Insomnia has been identified as a risk factor for development of mental illness, including doubling the risk of major depressive disorder and tripling the risk of any depressive or anxiety disorder.^7,8 It can also significantly increase the risk of alcohol abuse and psychosis.⁸

Sleep disturbances can worsen symptoms of diagnosed mental illness, including substance abuse, mood and psychotic disorders.^9-10 In one study, nearly 75% of patients with a diagnosis of schizophrenia or bipolar spectrum disorder had at least one type of sleep disturbance (insomnia, hypersomnia, or delayed sleep phase).¹⁰ This was almost twice the rate in healthy controls. Importantly, compared with well-rested subjects with mental illness in this study, sleep-disordered participants had higher rates of negative and depressive symptoms on the Positive and Negative Syndrome Scale, as well as significantly lower function via the global assessment of functioning.^11,12

Additional data suggests simply being awake during the night (00:00-05:59) elevates risk of suicide. The mean incident rate of completed suicide in one study was a striking four times the rate noted during daytime hours (06:00-23:59 ) (P < .001).¹³

Although insomnia symptoms can resolve after relief from a particular life stressor, as many as half of patients with more severe symptoms develop a chronic course.¹⁴ This then leads to an extended use of many types of sedative-hypnotics designed and studied primarily for short-term use.¹⁵ In a survey reviewing national use of prescription drugs for insomnia, as many as 20% of individuals use a medication to target insomnia in a given month.¹⁶

Fortunately, despite the many challenges posed by COVID-19, particularly for those with psychiatric illness and limited access to care, telehealth has become more readily available. Additionally, digital versions of evidence-based treatments specifically for sleep problems, such as cognitive-behavioral therapy for insomnia (CBT-I), are regularly being developed.

The benefits of CBT-I have been demonstrated repeatedly and it is recommended as the first line treatment for insomnia by the Clinical Guidelines of the American Academy of Sleep Medicine, the Centers for Disease Control and Prevention, and the National Institutes of Health.^17-21 Studies suggest benefits persist long-term, even after completing the therapy sessions, which differ in durability from medication choices.¹⁸

One group that may be particularly suited for treatment with CBT-I is women with insomnia during pregnancy or the postpartum period. In these women, options for treatment may be limited by risk of medication during breastfeeding, as well as difficulty traveling to a physician’s or therapist’s office to receive psychotherapy. However, two recent studies evaluated the use of digital CBT-I to treat insomnia during pregnancy and in the postpartum period, respectively.^22-23

In both studies,the same group of women with insomnia diagnosed during pregnancy were given six weekly 20-minute sessions of digital CBT-I or standard treatment for insomnia, including medication and psychotherapy per their usual provider.

By study end, the pregnant women receiving the CBT-I intervention not only had significantly improved severity of insomnia, they also experienced improved depression and anxiety symptoms, and a decrease in the use of prescription or over-the-counter sleep aides, compared with the standard treatment group, lowering the fetal exposure to medication during pregnancy.²²

In the more recent study, the same group was followed for 6 months post partum.²³ Results were again notable, with the women who received CBT-I reporting significantly less insomnia, as well as significantly lower rates of probable major depression at 3 and 6 months (18% vs. 4%, 10% vs. 0%, respectively.) They also exhibited lower rates of moderate to severe anxiety (17% vs. 4%) at 3 months, compared with those receiving standard care. With as many as one in seven women suffering from postpartum depression, these findings represent a substantial public health benefit.

In summary, insomnia is a critical area of focus for any provider diagnosing and treating psychiatric illness. Attempts to optimize sleep, whether through CBT-I or other psychotherapy approaches, or evidence-based medications dosed for appropriate lengths and at safe doses, should be a part of most, if not all, clinical encounters.

Dr. Reid is a board-certified psychiatrist and award-winning medical educator with a private practice in Philadelphia, as well as a clinical faculty role at the University of Pennsylvania, also in Philadelphia. She attended medical school at Columbia University, New York, and completed her psychiatry residency at the University of California, Los Angeles. Dr. Reid is a regular contributor to Psychology Today with her blog, “Think Like a Shrink,” and writes and podcasts as The Reflective Doc.

References

1. Voitsidis P et al. Psychiatry Res. 2020 Jul;289:113076. doi: 10.1016/j.psychres.2020.113076.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va.: American Psychiatric Publishing, 2013.

3. Ford DE and Kamerow DB. JAMA. 1989;262(11):1479-84. doi: 10.1001/jama.1989.03430110069030.

4. Ohayon MM and Roth T. J Psychiatr Res. Jan-Feb 2003;37(1):9-15. doi: 10.1016/s0022-3956(02)00052-3.

5. Seow LSE et al. J Ment Health. 2016 Dec;25(6):492-9. doi: 10.3109/09638237.2015.1124390.

6. Thase ME. J Clin Psychiatry. 1999;60 Suppl 17:28-31; discussion 46-8.

7. Baglioni C et al. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011.

8. Hertenstein E et al. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006.

9. Brower KJ et al. Medical Hypotheses. 2010;74(5):928-33. doi: 10.1016/j.mehy.2009.10.020.

10. Laskemoen JF et al. Compr Psychiatry. 2019 May;91:6-12. doi: 10.1016/j.comppsych.2019.02.006.

11. Kay SR et al. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

12. Hall R. Psychosomatics. May-Jun 1995;36(3):267-75. doi: 10.1016/S0033-3182(95)71666-8.

13. Perlis ML et al. J Clin Psychiatry. 2016 Jun;77(6):e726-33. doi: 10.4088/JCP.15m10131.

14. Morin CM et al. Arch Intern Med. 2009 Mar 9. doi: 10.1001/archinternmed.2008.610.

15. Cheung J et al. Sleep Med Clin. 2019 Jun;14(2):253-65. doi: 10.1016/j.jsmc.2019.01.006.

16. Bertisch SM et al. Sleep. 2014 Feb 1. doi: 10.5665/sleep.3410.

17. Okajima I et al. Sleep Biol Rhythms. 2010 Nov 28. doi: 10.1111/j.1479-8425.2010.00481.x.

18. Trauer JM et al. Ann Intern Med. 2015 Aug 4. doi: 10.7326/M14-2841.

19. Edinger J et al. J Clin Sleep Med. 2021 Feb 1. doi: 10.5664/jcsm.8986.

20. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/sleep/for-clinicians.html.

21. National Institutes of Health. Sleep Health. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/sleep-health.

22. Felder JN et al. JAMA Psychiatry. 2020;77(5):484-92. doi:10.1001/jamapsychiatry.2019.4491.

23. Felder JN et al. Sleep. 2022 Feb 14. doi: 10.1093/sleep/zsab280.

Insomnia rates continue to rise in the setting of the pandemic,¹ contributing to increasing rates of depression and anxiety, as well as worsening symptoms of other severe mental illnesses. Data suggests this symptom, defined as chronic sleep onset and/or sleep continuity problems associated with impaired daytime functioning, is common in psychiatric illnesses, and can worsen their course.²

The incidence of psychiatric illness in patients with insomnia is estimated at near 50%, with the highest rates found in mood disorders such as depression and bipolar disorder, as well as anxiety disorders.³ In patients with diagnosed major depressive disorder, insomnia rates can approach 90%.^4-6

Courtesy Dr. Jennifer Reid

Insomnia has been identified as a risk factor for development of mental illness, including doubling the risk of major depressive disorder and tripling the risk of any depressive or anxiety disorder.^7,8 It can also significantly increase the risk of alcohol abuse and psychosis.⁸

Sleep disturbances can worsen symptoms of diagnosed mental illness, including substance abuse, mood and psychotic disorders.^9-10 In one study, nearly 75% of patients with a diagnosis of schizophrenia or bipolar spectrum disorder had at least one type of sleep disturbance (insomnia, hypersomnia, or delayed sleep phase).¹⁰ This was almost twice the rate in healthy controls. Importantly, compared with well-rested subjects with mental illness in this study, sleep-disordered participants had higher rates of negative and depressive symptoms on the Positive and Negative Syndrome Scale, as well as significantly lower function via the global assessment of functioning.^11,12

Additional data suggests simply being awake during the night (00:00-05:59) elevates risk of suicide. The mean incident rate of completed suicide in one study was a striking four times the rate noted during daytime hours (06:00-23:59 ) (P < .001).¹³

Although insomnia symptoms can resolve after relief from a particular life stressor, as many as half of patients with more severe symptoms develop a chronic course.¹⁴ This then leads to an extended use of many types of sedative-hypnotics designed and studied primarily for short-term use.¹⁵ In a survey reviewing national use of prescription drugs for insomnia, as many as 20% of individuals use a medication to target insomnia in a given month.¹⁶

Fortunately, despite the many challenges posed by COVID-19, particularly for those with psychiatric illness and limited access to care, telehealth has become more readily available. Additionally, digital versions of evidence-based treatments specifically for sleep problems, such as cognitive-behavioral therapy for insomnia (CBT-I), are regularly being developed.

The benefits of CBT-I have been demonstrated repeatedly and it is recommended as the first line treatment for insomnia by the Clinical Guidelines of the American Academy of Sleep Medicine, the Centers for Disease Control and Prevention, and the National Institutes of Health.^17-21 Studies suggest benefits persist long-term, even after completing the therapy sessions, which differ in durability from medication choices.¹⁸

One group that may be particularly suited for treatment with CBT-I is women with insomnia during pregnancy or the postpartum period. In these women, options for treatment may be limited by risk of medication during breastfeeding, as well as difficulty traveling to a physician’s or therapist’s office to receive psychotherapy. However, two recent studies evaluated the use of digital CBT-I to treat insomnia during pregnancy and in the postpartum period, respectively.^22-23

In both studies,the same group of women with insomnia diagnosed during pregnancy were given six weekly 20-minute sessions of digital CBT-I or standard treatment for insomnia, including medication and psychotherapy per their usual provider.

By study end, the pregnant women receiving the CBT-I intervention not only had significantly improved severity of insomnia, they also experienced improved depression and anxiety symptoms, and a decrease in the use of prescription or over-the-counter sleep aides, compared with the standard treatment group, lowering the fetal exposure to medication during pregnancy.²²

In the more recent study, the same group was followed for 6 months post partum.²³ Results were again notable, with the women who received CBT-I reporting significantly less insomnia, as well as significantly lower rates of probable major depression at 3 and 6 months (18% vs. 4%, 10% vs. 0%, respectively.) They also exhibited lower rates of moderate to severe anxiety (17% vs. 4%) at 3 months, compared with those receiving standard care. With as many as one in seven women suffering from postpartum depression, these findings represent a substantial public health benefit.

In summary, insomnia is a critical area of focus for any provider diagnosing and treating psychiatric illness. Attempts to optimize sleep, whether through CBT-I or other psychotherapy approaches, or evidence-based medications dosed for appropriate lengths and at safe doses, should be a part of most, if not all, clinical encounters.

Dr. Reid is a board-certified psychiatrist and award-winning medical educator with a private practice in Philadelphia, as well as a clinical faculty role at the University of Pennsylvania, also in Philadelphia. She attended medical school at Columbia University, New York, and completed her psychiatry residency at the University of California, Los Angeles. Dr. Reid is a regular contributor to Psychology Today with her blog, “Think Like a Shrink,” and writes and podcasts as The Reflective Doc.

References

1. Voitsidis P et al. Psychiatry Res. 2020 Jul;289:113076. doi: 10.1016/j.psychres.2020.113076.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va.: American Psychiatric Publishing, 2013.

3. Ford DE and Kamerow DB. JAMA. 1989;262(11):1479-84. doi: 10.1001/jama.1989.03430110069030.

4. Ohayon MM and Roth T. J Psychiatr Res. Jan-Feb 2003;37(1):9-15. doi: 10.1016/s0022-3956(02)00052-3.

5. Seow LSE et al. J Ment Health. 2016 Dec;25(6):492-9. doi: 10.3109/09638237.2015.1124390.

6. Thase ME. J Clin Psychiatry. 1999;60 Suppl 17:28-31; discussion 46-8.

7. Baglioni C et al. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011.

8. Hertenstein E et al. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006.

9. Brower KJ et al. Medical Hypotheses. 2010;74(5):928-33. doi: 10.1016/j.mehy.2009.10.020.

10. Laskemoen JF et al. Compr Psychiatry. 2019 May;91:6-12. doi: 10.1016/j.comppsych.2019.02.006.

11. Kay SR et al. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

12. Hall R. Psychosomatics. May-Jun 1995;36(3):267-75. doi: 10.1016/S0033-3182(95)71666-8.

13. Perlis ML et al. J Clin Psychiatry. 2016 Jun;77(6):e726-33. doi: 10.4088/JCP.15m10131.

14. Morin CM et al. Arch Intern Med. 2009 Mar 9. doi: 10.1001/archinternmed.2008.610.

15. Cheung J et al. Sleep Med Clin. 2019 Jun;14(2):253-65. doi: 10.1016/j.jsmc.2019.01.006.

16. Bertisch SM et al. Sleep. 2014 Feb 1. doi: 10.5665/sleep.3410.

17. Okajima I et al. Sleep Biol Rhythms. 2010 Nov 28. doi: 10.1111/j.1479-8425.2010.00481.x.

18. Trauer JM et al. Ann Intern Med. 2015 Aug 4. doi: 10.7326/M14-2841.

19. Edinger J et al. J Clin Sleep Med. 2021 Feb 1. doi: 10.5664/jcsm.8986.

20. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/sleep/for-clinicians.html.

21. National Institutes of Health. Sleep Health. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/sleep-health.

22. Felder JN et al. JAMA Psychiatry. 2020;77(5):484-92. doi:10.1001/jamapsychiatry.2019.4491.

23. Felder JN et al. Sleep. 2022 Feb 14. doi: 10.1093/sleep/zsab280.

Anxiety and depression are common among individuals with inflammatory bowel disease (IBD) who are in remission, and the conditions are linked to unemployment and presenteeism, according to a prospective study.

Previous studies have found a heightened risk of anxiety and depression in IBD, as well as an association with poor treatment compliance and greater morbidity. Presenteeism, defined as reduced productivity due to a physical or mental condition, is increasingly recognized as an indirect economic cost of chronic conditions that may exact a higher cost than absenteeism.

Westend61/Getty Images

Anxiety and depression are common among individuals with inflammatory bowel disease (IBD) who are in remission, and the conditions are linked to unemployment and presenteeism, according to a prospective study.

Previous studies have found a heightened risk of anxiety and depression in IBD, as well as an association with poor treatment compliance and greater morbidity. Presenteeism, defined as reduced productivity due to a physical or mental condition, is increasingly recognized as an indirect economic cost of chronic conditions that may exact a higher cost than absenteeism.

Westend61/Getty Images

Anxiety and depression are common among individuals with inflammatory bowel disease (IBD) who are in remission, and the conditions are linked to unemployment and presenteeism, according to a prospective study.

Previous studies have found a heightened risk of anxiety and depression in IBD, as well as an association with poor treatment compliance and greater morbidity. Presenteeism, defined as reduced productivity due to a physical or mental condition, is increasingly recognized as an indirect economic cost of chronic conditions that may exact a higher cost than absenteeism.

Westend61/Getty Images

The use of bridging locoregional therapy (LRT) before liver transplantation in patients with hepatocellular carcinoma (HCC) has significantly increased in the United States within the past 15 years, a recent analysis suggests. Data show that liver transplant candidates with HCC who have elevated tumor burden and patients with more compensated liver disease have received a greater number of treatments while awaiting transplant.

Sebastian Kaulitzki/Science Photo Library

According to the researchers, led by Allison Kwong, MD, of Stanford (Calif.) University, liver transplant remains a curative option for individuals with unresectable HCC who meet prespecified size criteria. In the United States, a mandated waiting period of 6 months prior “to gaining exception points has been implemented” in an effort “to allow for consideration of tumor biology and reduce the disparities in waitlist dropout between HCC and non-HCC patients,” the researchers wrote.

Several forms of LRT are now available for HCC, including chemoembolization, external beam radiation, radioembolization, and radiofrequency or microwave ablation. In the liver transplant setting, these LRT options enable management of intrahepatic disease in patients who are waiting for liver transplant, Dr. Kwong and colleagues explained.

The researchers, who published their study findings online August 3 in Clinical Gastroenterology and Hepatology, sought to examine the national temporal trends and waitlist outcomes of LRT in 31,609 patients eligible for liver transplant with greater than or equal to 1 approved HCC exception application in the United States.

Patient data were obtained from the Organ Procurement and Transplantation Network database and comprised primary adult LT candidates who were listed from the years 2003 to 2018. The investigators assessed explant histology and performed multivariable competing risk analysis to examine the relationship between the type of first LRT and time to waitlist dropout.

The waitlist dropout variable was defined by list removal due to death or excessive illness. The researchers noted that list removal likely represents disease progression “beyond transplantable criteria and beyond which patients were unlikely to benefit from or be eligible for further LRT.”

In the study population, the median age was 59 years, and approximately 77% of patients were male. More than half (53.1%) of the cohort had hepatitis C as the predominant liver disease etiology. Patients had a median follow-up period of 214 days on the waitlist.

Most patients (79%) received deceased or living-donor transplants, and 18.6% of patients were removed from the waitlist. Between the 2003 and 2006 period, the median waitlist time was 123 days, but this median waitlist duration increased to 257 days for patients listed between 2015 and 2018.

A total of 34,610 LRTs were performed among 24,145 liver transplant candidates during the study period. From 2003 to 2018, the proportion of patients with greater than or equal to 1 LRT recorded in the database rose from 42.3% to 92.4%, respectively. Most patients (67.8%) who received liver-directed therapy had a single LRT, while 23.8% of patients had 2 LRTs, 6.2% had 3 LRTs, and 2.2% had greater than or equal to 4 LRTs.

The most frequent type of LRT performed was chemoembolization, followed by thermal ablation. Radioembolization increased from less than 5% in 2013 to 19% in 2018. Moreover, in 2018, chemoembolization accounted for 50% of LRTs, while thermal ablation accounted for 22% of LRTs.

The incidence rates of LRT per 100 waitlist days was above average in patients who had an initial tumor burden beyond the Milan criteria (0.188), an alpha-fetoprotein level of 21-40 (0.171) or 41-500 ng/mL (0.179), Child-Pugh class A (0.160), patients in short (0.151) and medium (0.154) wait-time regions, as well as patients who were listed following implementation of cap-and-delay in October 2015 (0.192).

In the multivariable competing-risk analysis for waitlist dropout, adjusting for initial tumor burden and AFP, Child-Pugh class, wait region, and listing era, no locoregional therapy was associated with an increased risk of waitlist dropout versus chemoembolization as the first LRT in a multivariable competing-risk analysis (subhazard ratio [sHR], 1.37; 95% CI, 1.28-1.47). The inverse probability of treatment weighting–adjusted analysis found an association between radioembolization, when compared with chemoembolization, and a reduced risk of waitlist dropout (sHR, 0.85; 95% CI, 0.81-0.89). Thermal ablation was also associated with a reduced risk of waitlist dropout, compared with chemoembolization (sHR, 0.95; 95% CI, 0.91-0.99). “Radioembolization and thermal ablation may be superior to chemoembolization and prove to be more cost-effective options, depending on the clinical context,” the researchers wrote.

The researchers noted that they were unable to distinguish patients who were removed from the waitlist between those with disease progression versus liver failure.

The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.

The use of bridging locoregional therapy (LRT) before liver transplantation in patients with hepatocellular carcinoma (HCC) has significantly increased in the United States within the past 15 years, a recent analysis suggests. Data show that liver transplant candidates with HCC who have elevated tumor burden and patients with more compensated liver disease have received a greater number of treatments while awaiting transplant.

Sebastian Kaulitzki/Science Photo Library

According to the researchers, led by Allison Kwong, MD, of Stanford (Calif.) University, liver transplant remains a curative option for individuals with unresectable HCC who meet prespecified size criteria. In the United States, a mandated waiting period of 6 months prior “to gaining exception points has been implemented” in an effort “to allow for consideration of tumor biology and reduce the disparities in waitlist dropout between HCC and non-HCC patients,” the researchers wrote.

Several forms of LRT are now available for HCC, including chemoembolization, external beam radiation, radioembolization, and radiofrequency or microwave ablation. In the liver transplant setting, these LRT options enable management of intrahepatic disease in patients who are waiting for liver transplant, Dr. Kwong and colleagues explained.

The researchers, who published their study findings online August 3 in Clinical Gastroenterology and Hepatology, sought to examine the national temporal trends and waitlist outcomes of LRT in 31,609 patients eligible for liver transplant with greater than or equal to 1 approved HCC exception application in the United States.

Patient data were obtained from the Organ Procurement and Transplantation Network database and comprised primary adult LT candidates who were listed from the years 2003 to 2018. The investigators assessed explant histology and performed multivariable competing risk analysis to examine the relationship between the type of first LRT and time to waitlist dropout.

The waitlist dropout variable was defined by list removal due to death or excessive illness. The researchers noted that list removal likely represents disease progression “beyond transplantable criteria and beyond which patients were unlikely to benefit from or be eligible for further LRT.”

In the study population, the median age was 59 years, and approximately 77% of patients were male. More than half (53.1%) of the cohort had hepatitis C as the predominant liver disease etiology. Patients had a median follow-up period of 214 days on the waitlist.

Most patients (79%) received deceased or living-donor transplants, and 18.6% of patients were removed from the waitlist. Between the 2003 and 2006 period, the median waitlist time was 123 days, but this median waitlist duration increased to 257 days for patients listed between 2015 and 2018.

A total of 34,610 LRTs were performed among 24,145 liver transplant candidates during the study period. From 2003 to 2018, the proportion of patients with greater than or equal to 1 LRT recorded in the database rose from 42.3% to 92.4%, respectively. Most patients (67.8%) who received liver-directed therapy had a single LRT, while 23.8% of patients had 2 LRTs, 6.2% had 3 LRTs, and 2.2% had greater than or equal to 4 LRTs.

The most frequent type of LRT performed was chemoembolization, followed by thermal ablation. Radioembolization increased from less than 5% in 2013 to 19% in 2018. Moreover, in 2018, chemoembolization accounted for 50% of LRTs, while thermal ablation accounted for 22% of LRTs.

The incidence rates of LRT per 100 waitlist days was above average in patients who had an initial tumor burden beyond the Milan criteria (0.188), an alpha-fetoprotein level of 21-40 (0.171) or 41-500 ng/mL (0.179), Child-Pugh class A (0.160), patients in short (0.151) and medium (0.154) wait-time regions, as well as patients who were listed following implementation of cap-and-delay in October 2015 (0.192).

In the multivariable competing-risk analysis for waitlist dropout, adjusting for initial tumor burden and AFP, Child-Pugh class, wait region, and listing era, no locoregional therapy was associated with an increased risk of waitlist dropout versus chemoembolization as the first LRT in a multivariable competing-risk analysis (subhazard ratio [sHR], 1.37; 95% CI, 1.28-1.47). The inverse probability of treatment weighting–adjusted analysis found an association between radioembolization, when compared with chemoembolization, and a reduced risk of waitlist dropout (sHR, 0.85; 95% CI, 0.81-0.89). Thermal ablation was also associated with a reduced risk of waitlist dropout, compared with chemoembolization (sHR, 0.95; 95% CI, 0.91-0.99). “Radioembolization and thermal ablation may be superior to chemoembolization and prove to be more cost-effective options, depending on the clinical context,” the researchers wrote.

The researchers noted that they were unable to distinguish patients who were removed from the waitlist between those with disease progression versus liver failure.

The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.

The use of bridging locoregional therapy (LRT) before liver transplantation in patients with hepatocellular carcinoma (HCC) has significantly increased in the United States within the past 15 years, a recent analysis suggests. Data show that liver transplant candidates with HCC who have elevated tumor burden and patients with more compensated liver disease have received a greater number of treatments while awaiting transplant.

Sebastian Kaulitzki/Science Photo Library

According to the researchers, led by Allison Kwong, MD, of Stanford (Calif.) University, liver transplant remains a curative option for individuals with unresectable HCC who meet prespecified size criteria. In the United States, a mandated waiting period of 6 months prior “to gaining exception points has been implemented” in an effort “to allow for consideration of tumor biology and reduce the disparities in waitlist dropout between HCC and non-HCC patients,” the researchers wrote.

Several forms of LRT are now available for HCC, including chemoembolization, external beam radiation, radioembolization, and radiofrequency or microwave ablation. In the liver transplant setting, these LRT options enable management of intrahepatic disease in patients who are waiting for liver transplant, Dr. Kwong and colleagues explained.

The researchers, who published their study findings online August 3 in Clinical Gastroenterology and Hepatology, sought to examine the national temporal trends and waitlist outcomes of LRT in 31,609 patients eligible for liver transplant with greater than or equal to 1 approved HCC exception application in the United States.

Patient data were obtained from the Organ Procurement and Transplantation Network database and comprised primary adult LT candidates who were listed from the years 2003 to 2018. The investigators assessed explant histology and performed multivariable competing risk analysis to examine the relationship between the type of first LRT and time to waitlist dropout.

The waitlist dropout variable was defined by list removal due to death or excessive illness. The researchers noted that list removal likely represents disease progression “beyond transplantable criteria and beyond which patients were unlikely to benefit from or be eligible for further LRT.”

In the study population, the median age was 59 years, and approximately 77% of patients were male. More than half (53.1%) of the cohort had hepatitis C as the predominant liver disease etiology. Patients had a median follow-up period of 214 days on the waitlist.

Most patients (79%) received deceased or living-donor transplants, and 18.6% of patients were removed from the waitlist. Between the 2003 and 2006 period, the median waitlist time was 123 days, but this median waitlist duration increased to 257 days for patients listed between 2015 and 2018.

A total of 34,610 LRTs were performed among 24,145 liver transplant candidates during the study period. From 2003 to 2018, the proportion of patients with greater than or equal to 1 LRT recorded in the database rose from 42.3% to 92.4%, respectively. Most patients (67.8%) who received liver-directed therapy had a single LRT, while 23.8% of patients had 2 LRTs, 6.2% had 3 LRTs, and 2.2% had greater than or equal to 4 LRTs.

The most frequent type of LRT performed was chemoembolization, followed by thermal ablation. Radioembolization increased from less than 5% in 2013 to 19% in 2018. Moreover, in 2018, chemoembolization accounted for 50% of LRTs, while thermal ablation accounted for 22% of LRTs.

The incidence rates of LRT per 100 waitlist days was above average in patients who had an initial tumor burden beyond the Milan criteria (0.188), an alpha-fetoprotein level of 21-40 (0.171) or 41-500 ng/mL (0.179), Child-Pugh class A (0.160), patients in short (0.151) and medium (0.154) wait-time regions, as well as patients who were listed following implementation of cap-and-delay in October 2015 (0.192).

In the multivariable competing-risk analysis for waitlist dropout, adjusting for initial tumor burden and AFP, Child-Pugh class, wait region, and listing era, no locoregional therapy was associated with an increased risk of waitlist dropout versus chemoembolization as the first LRT in a multivariable competing-risk analysis (subhazard ratio [sHR], 1.37; 95% CI, 1.28-1.47). The inverse probability of treatment weighting–adjusted analysis found an association between radioembolization, when compared with chemoembolization, and a reduced risk of waitlist dropout (sHR, 0.85; 95% CI, 0.81-0.89). Thermal ablation was also associated with a reduced risk of waitlist dropout, compared with chemoembolization (sHR, 0.95; 95% CI, 0.91-0.99). “Radioembolization and thermal ablation may be superior to chemoembolization and prove to be more cost-effective options, depending on the clinical context,” the researchers wrote.

The researchers noted that they were unable to distinguish patients who were removed from the waitlist between those with disease progression versus liver failure.

The researchers reported no conflicts of interest with the pharmaceutical industry. The study received no industry funding.

Spokane, Washington, was supposed to be the center of the Department of Veterans Affairs’ tech reinvention, the first site in the agency’s decade-long project to change its medical records software. But one morning in early March, the latest system malfunction made some clinicians snap.

At Spokane’s Mann-Grandstaff VA Medical Center, the records system — developed by Cerner Corp., based in North Kansas City, Missouri — went down. Staffers, inside the hospital and its outpatient facilities, were back to relying on pen and paper. Computerized schedules were inaccessible. Physicians couldn’t enter new orders or change patients’ medications.

By the next day, the electronic health records were only partially available. Dozens of records remained “sequestered,” meaning that doctors and nurses struggled to update patient charts.

The snafu, the latest in a series at Mann-Grandstaff, heightened Spokane medical staff members’ frustration with a system that has been problematic since it was installed a year and a half ago. The VA said no patients had been harmed because of the problems.

But physicians on the ground there said it’s only a matter of time before serious safety problems — those causing injury or death — emerge, pointing to the program’s ongoing weaknesses amid VA leadership’s full-bore push toward implementation nationwide. One provider said she was glad she didn’t have a relative in Mann-Grandstaff.

The one-two punch of a dangerous outage and staff grievances is the latest setback in the VA’s more than $16 billion effort to upgrade its record-keeping technology. The issues have at times forced clinicians to see fewer patients and file tens of thousands of requests for help to Cerner with patient-safety problems, congressional and agency watchdog reviews show.

If those issues multiply over the vast VA system — which employs more than a quarter-million workers and serves 6.3 million active patients — it could create rampant patient-safety and productivity problems. Despite the VA’s goals of using the technology upgrade to provide seamless records for patients from enlistment in the military until discharge, the doctors and clinicians who spoke to KHN are convinced that the problems experienced in Spokane will be repeated again and again.

The records system, scheduled for deployment at multiple VA facilities in the Pacific Northwest in the coming weeks and months, most recently rolled out at Jonathan M. Wainwright Memorial VA Medical Center in Walla Walla, Washington.

Both Cerner and Mann-Grandstaff officials declined to comment and referred KHN to officials at VA headquarters in Washington, D.C.

“If it’s a total meltdown” in Walla Walla, said Katie Purswell, the American Legion’s director of veterans affairs and rehabilitation, it’s a problem for the department and its decade-long initiative. Initial impressions from staffers are positive, but the issues in Spokane appeared over the course of weeks after the system was turned on.

The distress was particularly acute in early March. On March 2, Cerner turned on a software update to a database containing patient identification information. Problems emerged the next morning. In the record of a patient who was checking in for surgery, staff members discovered incorrect data, including gender information for a different patient. About an hour later, a staffer from the national VA’s medical records office told some clinicians at Mann-Grandstaff to “log out.”

Robert Fischer, Mann-Grandstaff’s medical center director, sent a dire warning later that morning. “Assume all electronic data is corrupted/inaccurate,” Fischer said in an email. He urged clinicians to limit orders for lab work, imaging studies, and medications. The facility shifted to “downtime procedures,” meaning a reliance on paper. 

Some staffers didn’t absorb the late-morning message and continued entering information in the mixed-up records, adding to the stew of erroneous data.

According to information provided to Congress later by the VA, Cerner had informed Mann-Grandstaff of a “complete degradation” the night before — leading to questions from staffers about why it took until late morning the next day to shut down the system. Agency spokesperson Erin Crowe told KHN there wasn’t any delay in notifying staff.

Problems stretched into the following week. Some records — 70 as of March 10, according to a briefing provided to Congress — remained unusable while auditors tried to ascertain what information had been mixed in from other charts. This left clinicians in some instances unable to keep track of patients’ care. Doctors said it became a confusing and chaotic environment. They couldn’t, for example, help patients refill prescriptions.

Members of Congress are concerned — not only about the outage but also VA’s explanations about it. In a letter to agency leadership, the leading Republicans on the House Veterans’ Affairs Committee and the subcommittee overseeing technology, Rep. Mike Bost of Illinois and Rep. Matt Rosendale of Montana, expressed worries the agency was “soft-pedal[ing]” its communications and argued that veterans were misled by assurances that records had been corrected.

The full committee plans to do a deeper examination soon. It has scheduled a closed-door roundtable with VA staffers from Spokane and Walla Walla on April 5.

The outage deepened unhappiness at Mann-Grandstaff. Clinicians there were already frazzled by a deeply buggy system. Downtime was common, a congressional aide told KHN.

A March 17 VA inspector general report documented nearly 39,000 requests for technical help or improvement since the October 2020 deployment of the new records system. Cerner employees often closed requests without resolving the underlying problems, the report said. Mann-Grandstaff staffers became disengaged or devised shortcuts to bypass the malfunctioning software, the inspector general wrote — each a potential root of patient-safety incidents.

The department said the shortcuts — or workarounds — aren’t its policy. “Workarounds are not authorized nor encouraged,” Crowe said.

The Biden administration tried to overhaul the software initiative, putting the program on hiatus before installing new leadership in the medical records office at the end of 2021. But by then, low morale had sunk in. “People in Spokane VA are … demoralized and unhappy,” Rep. Frank Mrvan (D-Ind.), chair of the House subcommittee focused on the VA’s technology modernization programs, told agency leaders during a November congressional hearing. He said staffers told him they felt as though they were beating their heads against a wall to make things function.

Other observers shared Mrvan’s concerns.

Purswell of the American Legion questioned whether appropriate steps are being taken to prepare the Walla Walla facility and its staff for the technology rollout. She asked whether staffers feel as if the Cerner system has been thrust upon them or are excited about the change.

Whether the VA has been persuasive about the benefits of the program is unclear. “I think it’s incumbent on us to demonstrate it’s not a loss,” said Dr. Terry Adirim, the leader of the VA office in charge of implementing the new records technology. “We might have dropped the ball on explaining what a benefit this is.”

Indeed, Adirim conducted a virtual town hall meeting March 21 for veterans in the Walla Walla area — where she was pressed about the problems in Spokane. “If Spokane has been a year figuring this out, why is this moving forward?” one questioner asked, expressing a point made frequently during the call. Adirim said the VA had made “thousands of changes” since the initial rollout.

Medical staffers at the Spokane and Walla Walla VA facilities are part of informal networks sharing their often-negative experiences about the program despite a perception among staff members that dissent will hurt their careers.

Adirim thinks negative feelings can be addressed by stepping up technical support. She also said training programs have been overhauled since the deployment in Spokane. Bottom line: The VA is proceeding.

“People want to revert back to what they did before,” Adirim said, but that’s not going to happen.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Subscribe to KHN's free Morning Briefing.

Spokane, Washington, was supposed to be the center of the Department of Veterans Affairs’ tech reinvention, the first site in the agency’s decade-long project to change its medical records software. But one morning in early March, the latest system malfunction made some clinicians snap.

At Spokane’s Mann-Grandstaff VA Medical Center, the records system — developed by Cerner Corp., based in North Kansas City, Missouri — went down. Staffers, inside the hospital and its outpatient facilities, were back to relying on pen and paper. Computerized schedules were inaccessible. Physicians couldn’t enter new orders or change patients’ medications.

By the next day, the electronic health records were only partially available. Dozens of records remained “sequestered,” meaning that doctors and nurses struggled to update patient charts.

The snafu, the latest in a series at Mann-Grandstaff, heightened Spokane medical staff members’ frustration with a system that has been problematic since it was installed a year and a half ago. The VA said no patients had been harmed because of the problems.

But physicians on the ground there said it’s only a matter of time before serious safety problems — those causing injury or death — emerge, pointing to the program’s ongoing weaknesses amid VA leadership’s full-bore push toward implementation nationwide. One provider said she was glad she didn’t have a relative in Mann-Grandstaff.

The one-two punch of a dangerous outage and staff grievances is the latest setback in the VA’s more than $16 billion effort to upgrade its record-keeping technology. The issues have at times forced clinicians to see fewer patients and file tens of thousands of requests for help to Cerner with patient-safety problems, congressional and agency watchdog reviews show.

If those issues multiply over the vast VA system — which employs more than a quarter-million workers and serves 6.3 million active patients — it could create rampant patient-safety and productivity problems. Despite the VA’s goals of using the technology upgrade to provide seamless records for patients from enlistment in the military until discharge, the doctors and clinicians who spoke to KHN are convinced that the problems experienced in Spokane will be repeated again and again.

The records system, scheduled for deployment at multiple VA facilities in the Pacific Northwest in the coming weeks and months, most recently rolled out at Jonathan M. Wainwright Memorial VA Medical Center in Walla Walla, Washington.

Both Cerner and Mann-Grandstaff officials declined to comment and referred KHN to officials at VA headquarters in Washington, D.C.

“If it’s a total meltdown” in Walla Walla, said Katie Purswell, the American Legion’s director of veterans affairs and rehabilitation, it’s a problem for the department and its decade-long initiative. Initial impressions from staffers are positive, but the issues in Spokane appeared over the course of weeks after the system was turned on.

The distress was particularly acute in early March. On March 2, Cerner turned on a software update to a database containing patient identification information. Problems emerged the next morning. In the record of a patient who was checking in for surgery, staff members discovered incorrect data, including gender information for a different patient. About an hour later, a staffer from the national VA’s medical records office told some clinicians at Mann-Grandstaff to “log out.”

Robert Fischer, Mann-Grandstaff’s medical center director, sent a dire warning later that morning. “Assume all electronic data is corrupted/inaccurate,” Fischer said in an email. He urged clinicians to limit orders for lab work, imaging studies, and medications. The facility shifted to “downtime procedures,” meaning a reliance on paper. 

Some staffers didn’t absorb the late-morning message and continued entering information in the mixed-up records, adding to the stew of erroneous data.

According to information provided to Congress later by the VA, Cerner had informed Mann-Grandstaff of a “complete degradation” the night before — leading to questions from staffers about why it took until late morning the next day to shut down the system. Agency spokesperson Erin Crowe told KHN there wasn’t any delay in notifying staff.

Problems stretched into the following week. Some records — 70 as of March 10, according to a briefing provided to Congress — remained unusable while auditors tried to ascertain what information had been mixed in from other charts. This left clinicians in some instances unable to keep track of patients’ care. Doctors said it became a confusing and chaotic environment. They couldn’t, for example, help patients refill prescriptions.

Members of Congress are concerned — not only about the outage but also VA’s explanations about it. In a letter to agency leadership, the leading Republicans on the House Veterans’ Affairs Committee and the subcommittee overseeing technology, Rep. Mike Bost of Illinois and Rep. Matt Rosendale of Montana, expressed worries the agency was “soft-pedal[ing]” its communications and argued that veterans were misled by assurances that records had been corrected.

The full committee plans to do a deeper examination soon. It has scheduled a closed-door roundtable with VA staffers from Spokane and Walla Walla on April 5.

The outage deepened unhappiness at Mann-Grandstaff. Clinicians there were already frazzled by a deeply buggy system. Downtime was common, a congressional aide told KHN.

A March 17 VA inspector general report documented nearly 39,000 requests for technical help or improvement since the October 2020 deployment of the new records system. Cerner employees often closed requests without resolving the underlying problems, the report said. Mann-Grandstaff staffers became disengaged or devised shortcuts to bypass the malfunctioning software, the inspector general wrote — each a potential root of patient-safety incidents.

The department said the shortcuts — or workarounds — aren’t its policy. “Workarounds are not authorized nor encouraged,” Crowe said.

The Biden administration tried to overhaul the software initiative, putting the program on hiatus before installing new leadership in the medical records office at the end of 2021. But by then, low morale had sunk in. “People in Spokane VA are … demoralized and unhappy,” Rep. Frank Mrvan (D-Ind.), chair of the House subcommittee focused on the VA’s technology modernization programs, told agency leaders during a November congressional hearing. He said staffers told him they felt as though they were beating their heads against a wall to make things function.

Other observers shared Mrvan’s concerns.

Purswell of the American Legion questioned whether appropriate steps are being taken to prepare the Walla Walla facility and its staff for the technology rollout. She asked whether staffers feel as if the Cerner system has been thrust upon them or are excited about the change.

Whether the VA has been persuasive about the benefits of the program is unclear. “I think it’s incumbent on us to demonstrate it’s not a loss,” said Dr. Terry Adirim, the leader of the VA office in charge of implementing the new records technology. “We might have dropped the ball on explaining what a benefit this is.”

Indeed, Adirim conducted a virtual town hall meeting March 21 for veterans in the Walla Walla area — where she was pressed about the problems in Spokane. “If Spokane has been a year figuring this out, why is this moving forward?” one questioner asked, expressing a point made frequently during the call. Adirim said the VA had made “thousands of changes” since the initial rollout.

Medical staffers at the Spokane and Walla Walla VA facilities are part of informal networks sharing their often-negative experiences about the program despite a perception among staff members that dissent will hurt their careers.

Adirim thinks negative feelings can be addressed by stepping up technical support. She also said training programs have been overhauled since the deployment in Spokane. Bottom line: The VA is proceeding.

“People want to revert back to what they did before,” Adirim said, but that’s not going to happen.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Subscribe to KHN's free Morning Briefing.

Spokane, Washington, was supposed to be the center of the Department of Veterans Affairs’ tech reinvention, the first site in the agency’s decade-long project to change its medical records software. But one morning in early March, the latest system malfunction made some clinicians snap.

At Spokane’s Mann-Grandstaff VA Medical Center, the records system — developed by Cerner Corp., based in North Kansas City, Missouri — went down. Staffers, inside the hospital and its outpatient facilities, were back to relying on pen and paper. Computerized schedules were inaccessible. Physicians couldn’t enter new orders or change patients’ medications.

By the next day, the electronic health records were only partially available. Dozens of records remained “sequestered,” meaning that doctors and nurses struggled to update patient charts.

The snafu, the latest in a series at Mann-Grandstaff, heightened Spokane medical staff members’ frustration with a system that has been problematic since it was installed a year and a half ago. The VA said no patients had been harmed because of the problems.

But physicians on the ground there said it’s only a matter of time before serious safety problems — those causing injury or death — emerge, pointing to the program’s ongoing weaknesses amid VA leadership’s full-bore push toward implementation nationwide. One provider said she was glad she didn’t have a relative in Mann-Grandstaff.

The one-two punch of a dangerous outage and staff grievances is the latest setback in the VA’s more than $16 billion effort to upgrade its record-keeping technology. The issues have at times forced clinicians to see fewer patients and file tens of thousands of requests for help to Cerner with patient-safety problems, congressional and agency watchdog reviews show.

If those issues multiply over the vast VA system — which employs more than a quarter-million workers and serves 6.3 million active patients — it could create rampant patient-safety and productivity problems. Despite the VA’s goals of using the technology upgrade to provide seamless records for patients from enlistment in the military until discharge, the doctors and clinicians who spoke to KHN are convinced that the problems experienced in Spokane will be repeated again and again.

The records system, scheduled for deployment at multiple VA facilities in the Pacific Northwest in the coming weeks and months, most recently rolled out at Jonathan M. Wainwright Memorial VA Medical Center in Walla Walla, Washington.

Both Cerner and Mann-Grandstaff officials declined to comment and referred KHN to officials at VA headquarters in Washington, D.C.

“If it’s a total meltdown” in Walla Walla, said Katie Purswell, the American Legion’s director of veterans affairs and rehabilitation, it’s a problem for the department and its decade-long initiative. Initial impressions from staffers are positive, but the issues in Spokane appeared over the course of weeks after the system was turned on.

The distress was particularly acute in early March. On March 2, Cerner turned on a software update to a database containing patient identification information. Problems emerged the next morning. In the record of a patient who was checking in for surgery, staff members discovered incorrect data, including gender information for a different patient. About an hour later, a staffer from the national VA’s medical records office told some clinicians at Mann-Grandstaff to “log out.”

Robert Fischer, Mann-Grandstaff’s medical center director, sent a dire warning later that morning. “Assume all electronic data is corrupted/inaccurate,” Fischer said in an email. He urged clinicians to limit orders for lab work, imaging studies, and medications. The facility shifted to “downtime procedures,” meaning a reliance on paper. 

Some staffers didn’t absorb the late-morning message and continued entering information in the mixed-up records, adding to the stew of erroneous data.

According to information provided to Congress later by the VA, Cerner had informed Mann-Grandstaff of a “complete degradation” the night before — leading to questions from staffers about why it took until late morning the next day to shut down the system. Agency spokesperson Erin Crowe told KHN there wasn’t any delay in notifying staff.

Problems stretched into the following week. Some records — 70 as of March 10, according to a briefing provided to Congress — remained unusable while auditors tried to ascertain what information had been mixed in from other charts. This left clinicians in some instances unable to keep track of patients’ care. Doctors said it became a confusing and chaotic environment. They couldn’t, for example, help patients refill prescriptions.

Members of Congress are concerned — not only about the outage but also VA’s explanations about it. In a letter to agency leadership, the leading Republicans on the House Veterans’ Affairs Committee and the subcommittee overseeing technology, Rep. Mike Bost of Illinois and Rep. Matt Rosendale of Montana, expressed worries the agency was “soft-pedal[ing]” its communications and argued that veterans were misled by assurances that records had been corrected.

The full committee plans to do a deeper examination soon. It has scheduled a closed-door roundtable with VA staffers from Spokane and Walla Walla on April 5.

The outage deepened unhappiness at Mann-Grandstaff. Clinicians there were already frazzled by a deeply buggy system. Downtime was common, a congressional aide told KHN.

A March 17 VA inspector general report documented nearly 39,000 requests for technical help or improvement since the October 2020 deployment of the new records system. Cerner employees often closed requests without resolving the underlying problems, the report said. Mann-Grandstaff staffers became disengaged or devised shortcuts to bypass the malfunctioning software, the inspector general wrote — each a potential root of patient-safety incidents.

The department said the shortcuts — or workarounds — aren’t its policy. “Workarounds are not authorized nor encouraged,” Crowe said.

The Biden administration tried to overhaul the software initiative, putting the program on hiatus before installing new leadership in the medical records office at the end of 2021. But by then, low morale had sunk in. “People in Spokane VA are … demoralized and unhappy,” Rep. Frank Mrvan (D-Ind.), chair of the House subcommittee focused on the VA’s technology modernization programs, told agency leaders during a November congressional hearing. He said staffers told him they felt as though they were beating their heads against a wall to make things function.

Other observers shared Mrvan’s concerns.

Purswell of the American Legion questioned whether appropriate steps are being taken to prepare the Walla Walla facility and its staff for the technology rollout. She asked whether staffers feel as if the Cerner system has been thrust upon them or are excited about the change.

Whether the VA has been persuasive about the benefits of the program is unclear. “I think it’s incumbent on us to demonstrate it’s not a loss,” said Dr. Terry Adirim, the leader of the VA office in charge of implementing the new records technology. “We might have dropped the ball on explaining what a benefit this is.”

Indeed, Adirim conducted a virtual town hall meeting March 21 for veterans in the Walla Walla area — where she was pressed about the problems in Spokane. “If Spokane has been a year figuring this out, why is this moving forward?” one questioner asked, expressing a point made frequently during the call. Adirim said the VA had made “thousands of changes” since the initial rollout.

Medical staffers at the Spokane and Walla Walla VA facilities are part of informal networks sharing their often-negative experiences about the program despite a perception among staff members that dissent will hurt their careers.

Adirim thinks negative feelings can be addressed by stepping up technical support. She also said training programs have been overhauled since the deployment in Spokane. Bottom line: The VA is proceeding.

“People want to revert back to what they did before,” Adirim said, but that’s not going to happen.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Subscribe to KHN's free Morning Briefing.

The Diagnosis: Reactive Perforating Collagenosis

Reactive perforating collagenosis (RPC) may be either acquired or inherited. It is 1 of 4 classical forms of transepithelial elimination, which also includes elastosis perforans serpiginosa (EPS) as well as perforating folliculitis and Kyrle disease. These 4 forms of transepithelial elimination share characteristics of the elimination of altered dermal components through the epidermis.¹ The acquired subtype of RPC frequently occurs in patients with diabetes mellitus and end-stage renal disease,² both present in our patient.

Clinical presentation typically shows pruritic hyperkeratotic papules with a central crater filled with crust that frequently are distributed on the extensor surfaces of the extremities, often in a linear pattern.³ The perforating papules and nodules occasionally may involve the trunk and face.⁴ Histopathologic examination is characterized by the elimination of altered collagen through the epidermis. Established lesions may show a cup-shaped depression of the epidermis filled with a keratin plug. The underlying dermis will show vertically oriented basophilic collagen fibers with focal extrusion through the epidermis, and elastic fibers will be absent.⁵ The exact pathophysiology of this disease is unknown, but it may represent a cutaneous response to superficial trauma caused by intense scratching.⁶

Standard treatment protocols are not well established for this condition, but some evidence shows that a combination of treatments can help ameliorate symptoms, even if they are not curative.⁷ Treatments without strong evidence have included a wide range of topical, systemic, and other therapies. Case series and anecdotal reports have used retinoids, corticosteroids, menthol, antibiotics, allopurinol antihistamines, cryotherapy, and lasers.⁸ One case was treated with a combination of narrowband UVB phototherapy and doxycycline with resolution in approximately 6 weeks.⁹ Other cases have been cured using triple therapy with antihistamines, topical or injected steroids, and emollients or oral antibiotics.⁷ Evidence shows that there may be benefit to combining multiple different treatment types that target pruritus, inflammation, and collagen damage.^7,9 This disease usually cannot be cured, but it may be improved by the available treatments.

The differential diagnosis includes delusional parasitosis, EPS, perforating folliculitis, and prurigo nodularis. Delusional parasitosis also can be characterized by excoriated plaques and a sensation of parasites infesting the skin, as our patient described.¹⁰ However, it can be differentiated from RPC by the fact that it is a diagnosis of exclusion, which would not have the histopathologic findings of the elimination of collagen from the epidermis, as was demonstrated in our patient.¹¹ Elastosis perforans serpiginosa is in the same family of perforating diseases as RPC; however, EPS typically appears in children or young adults and often is associated with other genetic disorders. Physical examination in a patient with EPS would reveal keratotic papules in a serpiginous pattern, whereas our patient had discrete lesions without any serpiginous pattern. The histopathologic appearance of EPS would reveal plugs of elastic fibers rather than collagen fibers, as was demonstrated in our patient.⁸ Perforating folliculitis, while also demonstrating transepithelial elimination similar to RPC, would appear as erythematous follicular papules with small central keratotic plugs and histopathologic findings of a widely dilated follicle with a mass of keratotic debris.¹² Prurigo nodularis would appear as dome-shaped papulonodules with varying degrees of scale, crust, and erosion, with a histopathologic appearance of hyperplasia and thick hyperkeratosis.¹¹

Overall, the histopathology is paramount in differentiating RPC from the alternative diagnoses, with the extrusion of collagen from the epidermis not being seen in these other conditions. The coupling of the medical history (type 2 diabetes mellitus and end-stage renal disease) with the clinical presentation and skin biopsy findings confirmed the diagnosis of RPC.

The Diagnosis: Reactive Perforating Collagenosis

Reactive perforating collagenosis (RPC) may be either acquired or inherited. It is 1 of 4 classical forms of transepithelial elimination, which also includes elastosis perforans serpiginosa (EPS) as well as perforating folliculitis and Kyrle disease. These 4 forms of transepithelial elimination share characteristics of the elimination of altered dermal components through the epidermis.¹ The acquired subtype of RPC frequently occurs in patients with diabetes mellitus and end-stage renal disease,² both present in our patient.

Clinical presentation typically shows pruritic hyperkeratotic papules with a central crater filled with crust that frequently are distributed on the extensor surfaces of the extremities, often in a linear pattern.³ The perforating papules and nodules occasionally may involve the trunk and face.⁴ Histopathologic examination is characterized by the elimination of altered collagen through the epidermis. Established lesions may show a cup-shaped depression of the epidermis filled with a keratin plug. The underlying dermis will show vertically oriented basophilic collagen fibers with focal extrusion through the epidermis, and elastic fibers will be absent.⁵ The exact pathophysiology of this disease is unknown, but it may represent a cutaneous response to superficial trauma caused by intense scratching.⁶

Standard treatment protocols are not well established for this condition, but some evidence shows that a combination of treatments can help ameliorate symptoms, even if they are not curative.⁷ Treatments without strong evidence have included a wide range of topical, systemic, and other therapies. Case series and anecdotal reports have used retinoids, corticosteroids, menthol, antibiotics, allopurinol antihistamines, cryotherapy, and lasers.⁸ One case was treated with a combination of narrowband UVB phototherapy and doxycycline with resolution in approximately 6 weeks.⁹ Other cases have been cured using triple therapy with antihistamines, topical or injected steroids, and emollients or oral antibiotics.⁷ Evidence shows that there may be benefit to combining multiple different treatment types that target pruritus, inflammation, and collagen damage.^7,9 This disease usually cannot be cured, but it may be improved by the available treatments.

The differential diagnosis includes delusional parasitosis, EPS, perforating folliculitis, and prurigo nodularis. Delusional parasitosis also can be characterized by excoriated plaques and a sensation of parasites infesting the skin, as our patient described.¹⁰ However, it can be differentiated from RPC by the fact that it is a diagnosis of exclusion, which would not have the histopathologic findings of the elimination of collagen from the epidermis, as was demonstrated in our patient.¹¹ Elastosis perforans serpiginosa is in the same family of perforating diseases as RPC; however, EPS typically appears in children or young adults and often is associated with other genetic disorders. Physical examination in a patient with EPS would reveal keratotic papules in a serpiginous pattern, whereas our patient had discrete lesions without any serpiginous pattern. The histopathologic appearance of EPS would reveal plugs of elastic fibers rather than collagen fibers, as was demonstrated in our patient.⁸ Perforating folliculitis, while also demonstrating transepithelial elimination similar to RPC, would appear as erythematous follicular papules with small central keratotic plugs and histopathologic findings of a widely dilated follicle with a mass of keratotic debris.¹² Prurigo nodularis would appear as dome-shaped papulonodules with varying degrees of scale, crust, and erosion, with a histopathologic appearance of hyperplasia and thick hyperkeratosis.¹¹

Overall, the histopathology is paramount in differentiating RPC from the alternative diagnoses, with the extrusion of collagen from the epidermis not being seen in these other conditions. The coupling of the medical history (type 2 diabetes mellitus and end-stage renal disease) with the clinical presentation and skin biopsy findings confirmed the diagnosis of RPC.

The Diagnosis: Reactive Perforating Collagenosis

Reactive perforating collagenosis (RPC) may be either acquired or inherited. It is 1 of 4 classical forms of transepithelial elimination, which also includes elastosis perforans serpiginosa (EPS) as well as perforating folliculitis and Kyrle disease. These 4 forms of transepithelial elimination share characteristics of the elimination of altered dermal components through the epidermis.¹ The acquired subtype of RPC frequently occurs in patients with diabetes mellitus and end-stage renal disease,² both present in our patient.

Clinical presentation typically shows pruritic hyperkeratotic papules with a central crater filled with crust that frequently are distributed on the extensor surfaces of the extremities, often in a linear pattern.³ The perforating papules and nodules occasionally may involve the trunk and face.⁴ Histopathologic examination is characterized by the elimination of altered collagen through the epidermis. Established lesions may show a cup-shaped depression of the epidermis filled with a keratin plug. The underlying dermis will show vertically oriented basophilic collagen fibers with focal extrusion through the epidermis, and elastic fibers will be absent.⁵ The exact pathophysiology of this disease is unknown, but it may represent a cutaneous response to superficial trauma caused by intense scratching.⁶

Standard treatment protocols are not well established for this condition, but some evidence shows that a combination of treatments can help ameliorate symptoms, even if they are not curative.⁷ Treatments without strong evidence have included a wide range of topical, systemic, and other therapies. Case series and anecdotal reports have used retinoids, corticosteroids, menthol, antibiotics, allopurinol antihistamines, cryotherapy, and lasers.⁸ One case was treated with a combination of narrowband UVB phototherapy and doxycycline with resolution in approximately 6 weeks.⁹ Other cases have been cured using triple therapy with antihistamines, topical or injected steroids, and emollients or oral antibiotics.⁷ Evidence shows that there may be benefit to combining multiple different treatment types that target pruritus, inflammation, and collagen damage.^7,9 This disease usually cannot be cured, but it may be improved by the available treatments.

The differential diagnosis includes delusional parasitosis, EPS, perforating folliculitis, and prurigo nodularis. Delusional parasitosis also can be characterized by excoriated plaques and a sensation of parasites infesting the skin, as our patient described.¹⁰ However, it can be differentiated from RPC by the fact that it is a diagnosis of exclusion, which would not have the histopathologic findings of the elimination of collagen from the epidermis, as was demonstrated in our patient.¹¹ Elastosis perforans serpiginosa is in the same family of perforating diseases as RPC; however, EPS typically appears in children or young adults and often is associated with other genetic disorders. Physical examination in a patient with EPS would reveal keratotic papules in a serpiginous pattern, whereas our patient had discrete lesions without any serpiginous pattern. The histopathologic appearance of EPS would reveal plugs of elastic fibers rather than collagen fibers, as was demonstrated in our patient.⁸ Perforating folliculitis, while also demonstrating transepithelial elimination similar to RPC, would appear as erythematous follicular papules with small central keratotic plugs and histopathologic findings of a widely dilated follicle with a mass of keratotic debris.¹² Prurigo nodularis would appear as dome-shaped papulonodules with varying degrees of scale, crust, and erosion, with a histopathologic appearance of hyperplasia and thick hyperkeratosis.¹¹

Overall, the histopathology is paramount in differentiating RPC from the alternative diagnoses, with the extrusion of collagen from the epidermis not being seen in these other conditions. The coupling of the medical history (type 2 diabetes mellitus and end-stage renal disease) with the clinical presentation and skin biopsy findings confirmed the diagnosis of RPC.