Federal Practitioner

MAR DEL PLATA, ARGENTINA – In the “active aging” vision promoted by the World Health Organization (WHO), older adults stay physically active, independent, and involved. This concept, though well-intentioned, is not very realistic and could easily be discouraging to individuals suffering from the psychological or physical limitations of old age. It also does not account for diversity among individuals and across cultures. These conclusions were presented by the Geriatric Psychiatry Chapter of the Argentine Psychiatric Association at its XXXVI Argentine Congress of Psychiatry.

“The WHO’s proposal of active aging is a prescriptive, standardized ideology that seems to suggest that being active is the only healthy way to age. However, that’s only part of the picture, and a biased part at that. It doesn’t account for the broad spectrum of aging processes that come in many shades,” said Mariana Pedace, psychologist with the Adult Intensive Care department at the Italian Hospital in Buenos Aires and head of the Older Adults section of the civic association Project: Unite.

“The question is whether the idea of active aging is just one more way to create mandates or rules for older adults, which make up such a heterogeneous and diverse generation,” said Ana Laura Vega, MD, psychiatrist with the Mental Health Department at the Italian Hospital of Buenos Aires.

Might it be better to speak of aging “as expected” or “aging well”? Speakers at the conference did not reach a consensus on which word would be the best to replace the adjective “active.”

“I don’t really see why there has to be an additional term when, at other stages of life, we only talk about ‘infancy,’ ‘adolescence,’ or ‘middle age,’ ” said Dr. Vega.
 

A thorny issue

Since the late 1990s, the WHO has defined active aging as “the process of optimizing opportunities for health, participation, and security to enhance quality of life as people age.” This concept allows older adults to “realize their potential for physical, social, and mental well-being throughout the life course and to participate in society according to their needs, desires, and capacities, while providing them with adequate protection, security, and care when they require assistance.”

The organization clarifies that the word “active” refers to continuing participation in social, economic, cultural, spiritual, and civic affairs, not just the ability to be physically active or to participate in the labor force. “However, in practice, active aging programs invariably promote physical activity and exercise as having health and social benefits,” said sociologist Elizabeth Pike, PhD, head of the Research Unit in Sport, Physical Activity, and Aging at the University of Hertfordshire in the United Kingdom.

“The concept of active aging, as presented, is a thorny issue and can potentially be problematic,” said Dr. Pedace. Along with laying out a single prescriptive way to age healthily, which by default makes passive aging “abnormal,” it also ignores demographic, ethnographic, and cultural differences.

“Each culture has different values. The suggestion of aging well in terms of activity, autonomy, and a happy-go-lucky mindset clearly reflects Western capitalistic values. In Eastern cultures, elderly people occupy a position reflecting their experience and wisdom, while also maintaining a contemplative mindset, which is something that is held in high regard. They are at the heart of the family, and their role is to guide and counsel the younger generations,” said Dr. Pedace.

The specialist added that there are programs inspired by active aging that prioritize outward, dynamic, and observable activities to the detriment of activities that take place behind the scenes such as reflection, analysis, and contemplation. “Following this mindset, an older individual who spends their time in contemplation would be somewhat wasting their sunset years. This raises a problem, because as the years go by and death approaches, spiritual life begins to gain far more significance. And that’s not an activity that is valued or recommended in the terms of this program,” she said.

Dr. Pedace went on to say that another concern with the active-aging program is that it seems to minimize certain characteristics that are unique to old age. Resulting physical, cognitive, and emotional changes can lead to reduced activity but are merely idiosyncrasies of this stage in life and are not pathologic.

Cecilia Guerstein, psychiatrist with the Older Adults Division of Project: United in Buenos Aires, cited Julieta Oddone, PhD, a sociologist on aging who believes that the theory of activity informs the underlying supposition of most programs for older adults: that social activity in itself is beneficial and results in greater fulfillment in life. And that all older people need and desire to stay active and engaged. “The idea is that the more active they are, the happier they will be,” said Dr. Guerstein.

“But ‘doing things’ isn’t necessarily appreciated by every elderly person, nor does it automatically lead to their well-being. The fact that some find a sense of well-being from it doesn’t mean we have to always do the same activities across different contexts. There are ethnographic studies that show that there isn’t necessarily a relationship between activity and well-being, or true social integration,” said Dr. Pedace.
 

Not a burden

Practically speaking, few would question whether physical activity has health benefits and believe that it’s never too late to start moving. Among his more than 45 tips on how to live to a ripe old age and “ripen” slowly and nicely, George D. Lundberg, MD, who is 90 years old, gives six recommendations for exercise: walking at least 2 miles every day, trying to swim every day, learning and practicing the techniques of yoga, deliberately lifting heavy objects (resistance training), and working on balance.

“A key for health care professionals encouraging exercise among older adults is knowing what to listen for and how to identify situations that motivate the person to exercise. For example, it could be walking their granddaughter down to the ice cream parlor,” Carolina Díaz, MD, said in an interview. Dr. Díaz is a geriatrics physician and the medical director of the Hirsch nursing and rehab center for older people in San Miguel, Argentina, which is home to 180 residents with an average age of 82 years.

“Exercise shouldn’t be a burden. If someone has never gone on walks before, I wouldn’t make them walk just because they ought to. Maybe they discover well-being in meeting up with their grandchildren or reading with someone. We believe that well-being is related to mobility, but for someone to move, they need the motivation. And until they have that, there won’t be any change,” said Dr. Díaz.

She added that a physician-patient relationship must be forged and an intervention plan drafted that revolves around the person and focuses on his or her current problems such as loneliness, difficulty walking, or pain. “Based on those problems, we can draw up a plan in which physical activity may play a part; other times, it may not.”

Osvaldo Bodni, psychiatrist and psychoanalyst, former director of the Department for Older Adults within the Argentine Psychoanalytic Association and author of the book, Delegating Power in Human Aging: The Theory of Legacy and Passing the Baton) said in an interview: “Aging isn’t a disease, though it does increase vulnerability. The proposal of physical activity is not the only ‘antidote.’ In my opinion, serenity during aging provides even better protection against life’s storms.”

The physician went on to say, “Active aging programs promote physical activity because it’s easier to go on a walk with someone than it is to have a literature debate with them. However, the goal is to create a feeling of being part of a group. This isn’t bad, but it’s a replacement for family. Being part of a group has come to fill the place that was once filled by one’s children, grandchildren, and students.

“When the flood of change in modern society rushes in so quickly, there is a ‘programmed phase-out’ of knowledge, and the demand for experience drops off. It becomes less valuable, such that older adults often get more comfort from finding someone who is willing to show an interest in their stories. The best therapist is the one who listens; not necessarily the one who invites them on a walk or a bike ride,” concluded Dr. Bodni.

Dr. Vega, Dr. Guerstein, Dr. Díaz, Dr. Bodni, and Dr. Pedace have disclosed no relevant financial relationships.
 

This article was translated from the Medscape Spanish Edition . A version appeared on Medscape.com.

MAR DEL PLATA, ARGENTINA – In the “active aging” vision promoted by the World Health Organization (WHO), older adults stay physically active, independent, and involved. This concept, though well-intentioned, is not very realistic and could easily be discouraging to individuals suffering from the psychological or physical limitations of old age. It also does not account for diversity among individuals and across cultures. These conclusions were presented by the Geriatric Psychiatry Chapter of the Argentine Psychiatric Association at its XXXVI Argentine Congress of Psychiatry.

“The WHO’s proposal of active aging is a prescriptive, standardized ideology that seems to suggest that being active is the only healthy way to age. However, that’s only part of the picture, and a biased part at that. It doesn’t account for the broad spectrum of aging processes that come in many shades,” said Mariana Pedace, psychologist with the Adult Intensive Care department at the Italian Hospital in Buenos Aires and head of the Older Adults section of the civic association Project: Unite.

“The question is whether the idea of active aging is just one more way to create mandates or rules for older adults, which make up such a heterogeneous and diverse generation,” said Ana Laura Vega, MD, psychiatrist with the Mental Health Department at the Italian Hospital of Buenos Aires.

Might it be better to speak of aging “as expected” or “aging well”? Speakers at the conference did not reach a consensus on which word would be the best to replace the adjective “active.”

“I don’t really see why there has to be an additional term when, at other stages of life, we only talk about ‘infancy,’ ‘adolescence,’ or ‘middle age,’ ” said Dr. Vega.
 

A thorny issue

Since the late 1990s, the WHO has defined active aging as “the process of optimizing opportunities for health, participation, and security to enhance quality of life as people age.” This concept allows older adults to “realize their potential for physical, social, and mental well-being throughout the life course and to participate in society according to their needs, desires, and capacities, while providing them with adequate protection, security, and care when they require assistance.”

The organization clarifies that the word “active” refers to continuing participation in social, economic, cultural, spiritual, and civic affairs, not just the ability to be physically active or to participate in the labor force. “However, in practice, active aging programs invariably promote physical activity and exercise as having health and social benefits,” said sociologist Elizabeth Pike, PhD, head of the Research Unit in Sport, Physical Activity, and Aging at the University of Hertfordshire in the United Kingdom.

“The concept of active aging, as presented, is a thorny issue and can potentially be problematic,” said Dr. Pedace. Along with laying out a single prescriptive way to age healthily, which by default makes passive aging “abnormal,” it also ignores demographic, ethnographic, and cultural differences.

“Each culture has different values. The suggestion of aging well in terms of activity, autonomy, and a happy-go-lucky mindset clearly reflects Western capitalistic values. In Eastern cultures, elderly people occupy a position reflecting their experience and wisdom, while also maintaining a contemplative mindset, which is something that is held in high regard. They are at the heart of the family, and their role is to guide and counsel the younger generations,” said Dr. Pedace.

The specialist added that there are programs inspired by active aging that prioritize outward, dynamic, and observable activities to the detriment of activities that take place behind the scenes such as reflection, analysis, and contemplation. “Following this mindset, an older individual who spends their time in contemplation would be somewhat wasting their sunset years. This raises a problem, because as the years go by and death approaches, spiritual life begins to gain far more significance. And that’s not an activity that is valued or recommended in the terms of this program,” she said.

Dr. Pedace went on to say that another concern with the active-aging program is that it seems to minimize certain characteristics that are unique to old age. Resulting physical, cognitive, and emotional changes can lead to reduced activity but are merely idiosyncrasies of this stage in life and are not pathologic.

Cecilia Guerstein, psychiatrist with the Older Adults Division of Project: United in Buenos Aires, cited Julieta Oddone, PhD, a sociologist on aging who believes that the theory of activity informs the underlying supposition of most programs for older adults: that social activity in itself is beneficial and results in greater fulfillment in life. And that all older people need and desire to stay active and engaged. “The idea is that the more active they are, the happier they will be,” said Dr. Guerstein.

“But ‘doing things’ isn’t necessarily appreciated by every elderly person, nor does it automatically lead to their well-being. The fact that some find a sense of well-being from it doesn’t mean we have to always do the same activities across different contexts. There are ethnographic studies that show that there isn’t necessarily a relationship between activity and well-being, or true social integration,” said Dr. Pedace.
 

Not a burden

Practically speaking, few would question whether physical activity has health benefits and believe that it’s never too late to start moving. Among his more than 45 tips on how to live to a ripe old age and “ripen” slowly and nicely, George D. Lundberg, MD, who is 90 years old, gives six recommendations for exercise: walking at least 2 miles every day, trying to swim every day, learning and practicing the techniques of yoga, deliberately lifting heavy objects (resistance training), and working on balance.

“A key for health care professionals encouraging exercise among older adults is knowing what to listen for and how to identify situations that motivate the person to exercise. For example, it could be walking their granddaughter down to the ice cream parlor,” Carolina Díaz, MD, said in an interview. Dr. Díaz is a geriatrics physician and the medical director of the Hirsch nursing and rehab center for older people in San Miguel, Argentina, which is home to 180 residents with an average age of 82 years.

“Exercise shouldn’t be a burden. If someone has never gone on walks before, I wouldn’t make them walk just because they ought to. Maybe they discover well-being in meeting up with their grandchildren or reading with someone. We believe that well-being is related to mobility, but for someone to move, they need the motivation. And until they have that, there won’t be any change,” said Dr. Díaz.

She added that a physician-patient relationship must be forged and an intervention plan drafted that revolves around the person and focuses on his or her current problems such as loneliness, difficulty walking, or pain. “Based on those problems, we can draw up a plan in which physical activity may play a part; other times, it may not.”

Osvaldo Bodni, psychiatrist and psychoanalyst, former director of the Department for Older Adults within the Argentine Psychoanalytic Association and author of the book, Delegating Power in Human Aging: The Theory of Legacy and Passing the Baton) said in an interview: “Aging isn’t a disease, though it does increase vulnerability. The proposal of physical activity is not the only ‘antidote.’ In my opinion, serenity during aging provides even better protection against life’s storms.”

The physician went on to say, “Active aging programs promote physical activity because it’s easier to go on a walk with someone than it is to have a literature debate with them. However, the goal is to create a feeling of being part of a group. This isn’t bad, but it’s a replacement for family. Being part of a group has come to fill the place that was once filled by one’s children, grandchildren, and students.

“When the flood of change in modern society rushes in so quickly, there is a ‘programmed phase-out’ of knowledge, and the demand for experience drops off. It becomes less valuable, such that older adults often get more comfort from finding someone who is willing to show an interest in their stories. The best therapist is the one who listens; not necessarily the one who invites them on a walk or a bike ride,” concluded Dr. Bodni.

Dr. Vega, Dr. Guerstein, Dr. Díaz, Dr. Bodni, and Dr. Pedace have disclosed no relevant financial relationships.
 

This article was translated from the Medscape Spanish Edition . A version appeared on Medscape.com.

MAR DEL PLATA, ARGENTINA – In the “active aging” vision promoted by the World Health Organization (WHO), older adults stay physically active, independent, and involved. This concept, though well-intentioned, is not very realistic and could easily be discouraging to individuals suffering from the psychological or physical limitations of old age. It also does not account for diversity among individuals and across cultures. These conclusions were presented by the Geriatric Psychiatry Chapter of the Argentine Psychiatric Association at its XXXVI Argentine Congress of Psychiatry.

“The WHO’s proposal of active aging is a prescriptive, standardized ideology that seems to suggest that being active is the only healthy way to age. However, that’s only part of the picture, and a biased part at that. It doesn’t account for the broad spectrum of aging processes that come in many shades,” said Mariana Pedace, psychologist with the Adult Intensive Care department at the Italian Hospital in Buenos Aires and head of the Older Adults section of the civic association Project: Unite.

“The question is whether the idea of active aging is just one more way to create mandates or rules for older adults, which make up such a heterogeneous and diverse generation,” said Ana Laura Vega, MD, psychiatrist with the Mental Health Department at the Italian Hospital of Buenos Aires.

Might it be better to speak of aging “as expected” or “aging well”? Speakers at the conference did not reach a consensus on which word would be the best to replace the adjective “active.”

“I don’t really see why there has to be an additional term when, at other stages of life, we only talk about ‘infancy,’ ‘adolescence,’ or ‘middle age,’ ” said Dr. Vega.
 

A thorny issue

Since the late 1990s, the WHO has defined active aging as “the process of optimizing opportunities for health, participation, and security to enhance quality of life as people age.” This concept allows older adults to “realize their potential for physical, social, and mental well-being throughout the life course and to participate in society according to their needs, desires, and capacities, while providing them with adequate protection, security, and care when they require assistance.”

The organization clarifies that the word “active” refers to continuing participation in social, economic, cultural, spiritual, and civic affairs, not just the ability to be physically active or to participate in the labor force. “However, in practice, active aging programs invariably promote physical activity and exercise as having health and social benefits,” said sociologist Elizabeth Pike, PhD, head of the Research Unit in Sport, Physical Activity, and Aging at the University of Hertfordshire in the United Kingdom.

“The concept of active aging, as presented, is a thorny issue and can potentially be problematic,” said Dr. Pedace. Along with laying out a single prescriptive way to age healthily, which by default makes passive aging “abnormal,” it also ignores demographic, ethnographic, and cultural differences.

“Each culture has different values. The suggestion of aging well in terms of activity, autonomy, and a happy-go-lucky mindset clearly reflects Western capitalistic values. In Eastern cultures, elderly people occupy a position reflecting their experience and wisdom, while also maintaining a contemplative mindset, which is something that is held in high regard. They are at the heart of the family, and their role is to guide and counsel the younger generations,” said Dr. Pedace.

The specialist added that there are programs inspired by active aging that prioritize outward, dynamic, and observable activities to the detriment of activities that take place behind the scenes such as reflection, analysis, and contemplation. “Following this mindset, an older individual who spends their time in contemplation would be somewhat wasting their sunset years. This raises a problem, because as the years go by and death approaches, spiritual life begins to gain far more significance. And that’s not an activity that is valued or recommended in the terms of this program,” she said.

Dr. Pedace went on to say that another concern with the active-aging program is that it seems to minimize certain characteristics that are unique to old age. Resulting physical, cognitive, and emotional changes can lead to reduced activity but are merely idiosyncrasies of this stage in life and are not pathologic.

Cecilia Guerstein, psychiatrist with the Older Adults Division of Project: United in Buenos Aires, cited Julieta Oddone, PhD, a sociologist on aging who believes that the theory of activity informs the underlying supposition of most programs for older adults: that social activity in itself is beneficial and results in greater fulfillment in life. And that all older people need and desire to stay active and engaged. “The idea is that the more active they are, the happier they will be,” said Dr. Guerstein.

“But ‘doing things’ isn’t necessarily appreciated by every elderly person, nor does it automatically lead to their well-being. The fact that some find a sense of well-being from it doesn’t mean we have to always do the same activities across different contexts. There are ethnographic studies that show that there isn’t necessarily a relationship between activity and well-being, or true social integration,” said Dr. Pedace.
 

Not a burden

Practically speaking, few would question whether physical activity has health benefits and believe that it’s never too late to start moving. Among his more than 45 tips on how to live to a ripe old age and “ripen” slowly and nicely, George D. Lundberg, MD, who is 90 years old, gives six recommendations for exercise: walking at least 2 miles every day, trying to swim every day, learning and practicing the techniques of yoga, deliberately lifting heavy objects (resistance training), and working on balance.

“A key for health care professionals encouraging exercise among older adults is knowing what to listen for and how to identify situations that motivate the person to exercise. For example, it could be walking their granddaughter down to the ice cream parlor,” Carolina Díaz, MD, said in an interview. Dr. Díaz is a geriatrics physician and the medical director of the Hirsch nursing and rehab center for older people in San Miguel, Argentina, which is home to 180 residents with an average age of 82 years.

“Exercise shouldn’t be a burden. If someone has never gone on walks before, I wouldn’t make them walk just because they ought to. Maybe they discover well-being in meeting up with their grandchildren or reading with someone. We believe that well-being is related to mobility, but for someone to move, they need the motivation. And until they have that, there won’t be any change,” said Dr. Díaz.

She added that a physician-patient relationship must be forged and an intervention plan drafted that revolves around the person and focuses on his or her current problems such as loneliness, difficulty walking, or pain. “Based on those problems, we can draw up a plan in which physical activity may play a part; other times, it may not.”

Osvaldo Bodni, psychiatrist and psychoanalyst, former director of the Department for Older Adults within the Argentine Psychoanalytic Association and author of the book, Delegating Power in Human Aging: The Theory of Legacy and Passing the Baton) said in an interview: “Aging isn’t a disease, though it does increase vulnerability. The proposal of physical activity is not the only ‘antidote.’ In my opinion, serenity during aging provides even better protection against life’s storms.”

The physician went on to say, “Active aging programs promote physical activity because it’s easier to go on a walk with someone than it is to have a literature debate with them. However, the goal is to create a feeling of being part of a group. This isn’t bad, but it’s a replacement for family. Being part of a group has come to fill the place that was once filled by one’s children, grandchildren, and students.

“When the flood of change in modern society rushes in so quickly, there is a ‘programmed phase-out’ of knowledge, and the demand for experience drops off. It becomes less valuable, such that older adults often get more comfort from finding someone who is willing to show an interest in their stories. The best therapist is the one who listens; not necessarily the one who invites them on a walk or a bike ride,” concluded Dr. Bodni.

Dr. Vega, Dr. Guerstein, Dr. Díaz, Dr. Bodni, and Dr. Pedace have disclosed no relevant financial relationships.
 

This article was translated from the Medscape Spanish Edition . A version appeared on Medscape.com.

The identification of an antibody linked to spontaneous reversal of cardiac transthyretin amyloidosis may represent a novel approach to treatment of this normally universally progressive and fatal condition.

Cardiac transthyretin amyloidosis (also called ATTR amyloidosis cardiomyopathy or ATTR-CM) is a progressive disease and a cause of heart failure resulting from accumulation of the protein transthyretin, which misfolds and forms amyloid deposits on the walls of the heart, causing both systolic and diastolic dysfunction.

The condition is progressive and normally fatal within a few years of diagnosis. Treatment options are limited and aimed at slowing progression; nothing has been shown to reverse the course of the disease.

However, an international team of researchers is now reporting the discovery of three patients with ATTR-CM–associated heart failure in whom the condition resolved spontaneously, with reversion to near normal cardiac structure and function. On further investigation, it was found that these three patients had developed circulating polyclonal IgG antibodies to human ATTR amyloid.

They are hopeful that a monoclonal form of these antibodies could be developed and may represent a novel treatment, or even a cure, for the condition.

The researchers report their findings in a letter to the New England Journal of Medicine.

“We are very optimistic about this discovery of these antibodies. They could become the first treatment to clear the amyloid that causes this horribly progressive and fatal condition,” senior author Julian Gillmore, MD, head of the University College London Centre for Amyloidosis, based at the Royal Free Hospital, said in an interview.

“Obviously, there is a lot of work to do before we can say this is the case, but it is very exciting,” he added.

Dr. Gillmore explained how the antibodies were discovered. “This disease has a universally progressive course, but we had one patient who on a repeat appointment said he felt better and on detailed cardiac MRI imaging, we found that the amyloid in his heart had reduced. That is totally unheard of,” he said.

“We then looked back at our cohort of 1,663 patients with ATTR-cardiomyopathy, and we discovered two others who had also improved both on imaging and clinically,” Dr. Gillmore said.

Each of these three patients reported a reduction in symptoms, although they had not received any new or potentially disease-modifying treatments. None of the patients had had recent vaccinations, notable infections, or any clinical suggestion of myocarditis.

Clinical recovery was corroborated by substantial improvement or normalization of findings on echocardiography, serum biomarker levels, and results of cardiopulmonary exercise tests and scintigraphy.

Serial cardiac MRI scans confirmed near-complete regression of myocardial extracellular volume, coupled with remodeling to near-normal cardiac structure and function without scarring.

The researchers wondered whether the changes in these patients may have been brought about by an antibody response. On further investigation, they found antibodies in the three patients that bound specifically to ATTR amyloid deposits in a transgenic mouse model of the condition, and to synthetic ATTR amyloid. No such antibodies were present in the other 350 patients in the cohort with a typical clinical course.

“The cause and clinical significance of the anti-ATTR amyloid antibodies are intriguing and presently unclear. However, the clinical recovery of these patients establishes the unanticipated potential for reversibility of ATTR-CM and raises expectations for its treatment,” the researchers conclude.

Dr. Gillmore said they didn’t know why these three patients had these antibodies, while all the other patients did not. “There must be something different about these patients. We don’t know what that is at present, but we are looking hard.”

The researchers are hoping that after this publication, other centers caring for patients with ATTR-cardiomyopathy will look in their cohorts and see if they can identify other cases where there has been improvement.

“It is very plausible that they do have such cases, but they will be rare, as we all think of this disease as universally progressive and fatal,” Dr. Gillmore noted.

“We haven’t absolutely proven that the antibodies have caused the clearance of amyloid in these patients, but we strongly suspect this to be the case,” Dr. Gillmore said. The researchers are planning to try to confirm this by isolating the antibodies and treating the transgenic mice.

Dr. Gillmore attributed the current discovery to the development of novel imaging cardiac MRI techniques. “This allowed us to monitor closely the amyloid burden in the heart. The observation that this had diminished in these three patients was the breakthrough that led us to look for antibodies.”

Another antibody product directed against ATTR cardiomyopathy is also in development by Neurimmune, a Swiss biopharmaceutical company. A phase 1 study of this agent was recently published, suggesting that it appeared to reduce the amount of amyloid protein deposited in the heart.

Dr. Gillmore said the antibody they have detected is different from the Neurimmune product.

The research was supported by a British Heart Foundation Intermediate Clinical Research Fellowship, a Medical Research Council Career Development Award, and a project grant from the British Heart Foundation. Dr. Gillmore reports being a consultant or expert advisory board member for Alnylam Pharmaceuticals, AstraZeneca, ATTRalus, Eidos Therapeutics, Intellia Therapeutics, Ionis Pharmaceuticals, and Pfizer.

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

The identification of an antibody linked to spontaneous reversal of cardiac transthyretin amyloidosis may represent a novel approach to treatment of this normally universally progressive and fatal condition.

Cardiac transthyretin amyloidosis (also called ATTR amyloidosis cardiomyopathy or ATTR-CM) is a progressive disease and a cause of heart failure resulting from accumulation of the protein transthyretin, which misfolds and forms amyloid deposits on the walls of the heart, causing both systolic and diastolic dysfunction.

The condition is progressive and normally fatal within a few years of diagnosis. Treatment options are limited and aimed at slowing progression; nothing has been shown to reverse the course of the disease.

However, an international team of researchers is now reporting the discovery of three patients with ATTR-CM–associated heart failure in whom the condition resolved spontaneously, with reversion to near normal cardiac structure and function. On further investigation, it was found that these three patients had developed circulating polyclonal IgG antibodies to human ATTR amyloid.

They are hopeful that a monoclonal form of these antibodies could be developed and may represent a novel treatment, or even a cure, for the condition.

The researchers report their findings in a letter to the New England Journal of Medicine.

“We are very optimistic about this discovery of these antibodies. They could become the first treatment to clear the amyloid that causes this horribly progressive and fatal condition,” senior author Julian Gillmore, MD, head of the University College London Centre for Amyloidosis, based at the Royal Free Hospital, said in an interview.

“Obviously, there is a lot of work to do before we can say this is the case, but it is very exciting,” he added.

Dr. Gillmore explained how the antibodies were discovered. “This disease has a universally progressive course, but we had one patient who on a repeat appointment said he felt better and on detailed cardiac MRI imaging, we found that the amyloid in his heart had reduced. That is totally unheard of,” he said.

“We then looked back at our cohort of 1,663 patients with ATTR-cardiomyopathy, and we discovered two others who had also improved both on imaging and clinically,” Dr. Gillmore said.

Each of these three patients reported a reduction in symptoms, although they had not received any new or potentially disease-modifying treatments. None of the patients had had recent vaccinations, notable infections, or any clinical suggestion of myocarditis.

Clinical recovery was corroborated by substantial improvement or normalization of findings on echocardiography, serum biomarker levels, and results of cardiopulmonary exercise tests and scintigraphy.

Serial cardiac MRI scans confirmed near-complete regression of myocardial extracellular volume, coupled with remodeling to near-normal cardiac structure and function without scarring.

The researchers wondered whether the changes in these patients may have been brought about by an antibody response. On further investigation, they found antibodies in the three patients that bound specifically to ATTR amyloid deposits in a transgenic mouse model of the condition, and to synthetic ATTR amyloid. No such antibodies were present in the other 350 patients in the cohort with a typical clinical course.

“The cause and clinical significance of the anti-ATTR amyloid antibodies are intriguing and presently unclear. However, the clinical recovery of these patients establishes the unanticipated potential for reversibility of ATTR-CM and raises expectations for its treatment,” the researchers conclude.

Dr. Gillmore said they didn’t know why these three patients had these antibodies, while all the other patients did not. “There must be something different about these patients. We don’t know what that is at present, but we are looking hard.”

The researchers are hoping that after this publication, other centers caring for patients with ATTR-cardiomyopathy will look in their cohorts and see if they can identify other cases where there has been improvement.

“It is very plausible that they do have such cases, but they will be rare, as we all think of this disease as universally progressive and fatal,” Dr. Gillmore noted.

“We haven’t absolutely proven that the antibodies have caused the clearance of amyloid in these patients, but we strongly suspect this to be the case,” Dr. Gillmore said. The researchers are planning to try to confirm this by isolating the antibodies and treating the transgenic mice.

Dr. Gillmore attributed the current discovery to the development of novel imaging cardiac MRI techniques. “This allowed us to monitor closely the amyloid burden in the heart. The observation that this had diminished in these three patients was the breakthrough that led us to look for antibodies.”

Another antibody product directed against ATTR cardiomyopathy is also in development by Neurimmune, a Swiss biopharmaceutical company. A phase 1 study of this agent was recently published, suggesting that it appeared to reduce the amount of amyloid protein deposited in the heart.

Dr. Gillmore said the antibody they have detected is different from the Neurimmune product.

The research was supported by a British Heart Foundation Intermediate Clinical Research Fellowship, a Medical Research Council Career Development Award, and a project grant from the British Heart Foundation. Dr. Gillmore reports being a consultant or expert advisory board member for Alnylam Pharmaceuticals, AstraZeneca, ATTRalus, Eidos Therapeutics, Intellia Therapeutics, Ionis Pharmaceuticals, and Pfizer.

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

The identification of an antibody linked to spontaneous reversal of cardiac transthyretin amyloidosis may represent a novel approach to treatment of this normally universally progressive and fatal condition.

Cardiac transthyretin amyloidosis (also called ATTR amyloidosis cardiomyopathy or ATTR-CM) is a progressive disease and a cause of heart failure resulting from accumulation of the protein transthyretin, which misfolds and forms amyloid deposits on the walls of the heart, causing both systolic and diastolic dysfunction.

The condition is progressive and normally fatal within a few years of diagnosis. Treatment options are limited and aimed at slowing progression; nothing has been shown to reverse the course of the disease.

However, an international team of researchers is now reporting the discovery of three patients with ATTR-CM–associated heart failure in whom the condition resolved spontaneously, with reversion to near normal cardiac structure and function. On further investigation, it was found that these three patients had developed circulating polyclonal IgG antibodies to human ATTR amyloid.

They are hopeful that a monoclonal form of these antibodies could be developed and may represent a novel treatment, or even a cure, for the condition.

The researchers report their findings in a letter to the New England Journal of Medicine.

“We are very optimistic about this discovery of these antibodies. They could become the first treatment to clear the amyloid that causes this horribly progressive and fatal condition,” senior author Julian Gillmore, MD, head of the University College London Centre for Amyloidosis, based at the Royal Free Hospital, said in an interview.

“Obviously, there is a lot of work to do before we can say this is the case, but it is very exciting,” he added.

Dr. Gillmore explained how the antibodies were discovered. “This disease has a universally progressive course, but we had one patient who on a repeat appointment said he felt better and on detailed cardiac MRI imaging, we found that the amyloid in his heart had reduced. That is totally unheard of,” he said.

“We then looked back at our cohort of 1,663 patients with ATTR-cardiomyopathy, and we discovered two others who had also improved both on imaging and clinically,” Dr. Gillmore said.

Each of these three patients reported a reduction in symptoms, although they had not received any new or potentially disease-modifying treatments. None of the patients had had recent vaccinations, notable infections, or any clinical suggestion of myocarditis.

Clinical recovery was corroborated by substantial improvement or normalization of findings on echocardiography, serum biomarker levels, and results of cardiopulmonary exercise tests and scintigraphy.

Serial cardiac MRI scans confirmed near-complete regression of myocardial extracellular volume, coupled with remodeling to near-normal cardiac structure and function without scarring.

The researchers wondered whether the changes in these patients may have been brought about by an antibody response. On further investigation, they found antibodies in the three patients that bound specifically to ATTR amyloid deposits in a transgenic mouse model of the condition, and to synthetic ATTR amyloid. No such antibodies were present in the other 350 patients in the cohort with a typical clinical course.

“The cause and clinical significance of the anti-ATTR amyloid antibodies are intriguing and presently unclear. However, the clinical recovery of these patients establishes the unanticipated potential for reversibility of ATTR-CM and raises expectations for its treatment,” the researchers conclude.

Dr. Gillmore said they didn’t know why these three patients had these antibodies, while all the other patients did not. “There must be something different about these patients. We don’t know what that is at present, but we are looking hard.”

The researchers are hoping that after this publication, other centers caring for patients with ATTR-cardiomyopathy will look in their cohorts and see if they can identify other cases where there has been improvement.

“It is very plausible that they do have such cases, but they will be rare, as we all think of this disease as universally progressive and fatal,” Dr. Gillmore noted.

“We haven’t absolutely proven that the antibodies have caused the clearance of amyloid in these patients, but we strongly suspect this to be the case,” Dr. Gillmore said. The researchers are planning to try to confirm this by isolating the antibodies and treating the transgenic mice.

Dr. Gillmore attributed the current discovery to the development of novel imaging cardiac MRI techniques. “This allowed us to monitor closely the amyloid burden in the heart. The observation that this had diminished in these three patients was the breakthrough that led us to look for antibodies.”

Another antibody product directed against ATTR cardiomyopathy is also in development by Neurimmune, a Swiss biopharmaceutical company. A phase 1 study of this agent was recently published, suggesting that it appeared to reduce the amount of amyloid protein deposited in the heart.

Dr. Gillmore said the antibody they have detected is different from the Neurimmune product.

The research was supported by a British Heart Foundation Intermediate Clinical Research Fellowship, a Medical Research Council Career Development Award, and a project grant from the British Heart Foundation. Dr. Gillmore reports being a consultant or expert advisory board member for Alnylam Pharmaceuticals, AstraZeneca, ATTRalus, Eidos Therapeutics, Intellia Therapeutics, Ionis Pharmaceuticals, and Pfizer.

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

Women with moderate to severe psoriasis had a lower fertility rate, compared with age-matched peers without psoriasis, and overall, those with psoriasis had a slightly higher risk of pregnancy loss, compared with those who did not have the disease, in a U.K. cohort study.

Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.

“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”

To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.

Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.

The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Fertility, birth outcomes

When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.

As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.

In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.

However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.

“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”

They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”

Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.

This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.

“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”

The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.

Women with moderate to severe psoriasis had a lower fertility rate, compared with age-matched peers without psoriasis, and overall, those with psoriasis had a slightly higher risk of pregnancy loss, compared with those who did not have the disease, in a U.K. cohort study.

Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.

“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”

To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.

Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.

The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Fertility, birth outcomes

When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.

As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.

In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.

However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.

“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”

They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”

Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.

This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.

“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”

The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.

Women with moderate to severe psoriasis had a lower fertility rate, compared with age-matched peers without psoriasis, and overall, those with psoriasis had a slightly higher risk of pregnancy loss, compared with those who did not have the disease, in a U.K. cohort study.

Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.

“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”

To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.

Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.

The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Fertility, birth outcomes

When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.

As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.

In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.

However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.

“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”

They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”

Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.

This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.

“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”

The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Frailty is an age-associated, nonspecific vulnerability to adverse health outcomes. Frailty can also be described as a complex of symptoms characterized by impaired stress tolerance due to a decline in the functionality of different organs.¹ The prevalence of frailty varies widely depending on the method of measurement and the population studied.^2-4 It is a nonconstant factor that increases with age. A deficit accumulation frailty index (FI) is one method used to measure frailty.⁵ This approach sees frailty as a multidimensional risk state measured by quantity rather than the nature of health concerns. A deficit accumulation FI does not require physical testing but correlates well with other phenotypic FIs.⁶ It is, however, time consuming, as ≥ 30 deficits need to be measured to offer greater stability to the frailty estimate.

Health care is seeing increasing utilization of big data analytics to derive predictive models and help with resource allocation. There are currently 2 existing automated tools to predict health care utilization and mortality at the US Department of Veterans Affairs (VA): the VA Frailty Index (VA-FI-10) and the Care Assessment Need (CAN). VA-FI-10 is an International Statistical Classification of Diseases, Tenth Revision (ICD-10) update of the VA-FI that was created in March 2021. The VA-FI-10 is a claims-based frailty assessment tool using 31 health deficits. Calculating the VA-FI-10 requires defining an index date and lookback period (typically 3 years) relative to which it will be calculated.⁷

CAN is a set of risk-stratifying statistical models run on veterans receiving VA primary care services as part of a patient aligned care team (PACT) using electronic health record data.⁸ Each veteran is stratified based on the individual’s risks of hospitalization, death, and hospitalization or death. These 3 events are predicted for 90-day and 1-year time periods for a total of 6 distinct outcomes. CAN is currently on its third iteration (CAN 2.5) and scores range from 0 (low) to 99 (high). CAN scores are updated weekly. The 1-year hospitalization probabilities for all patients range from 0.8% to 93.1%. For patients with a CAN score of 50, the probability of being hospitalized within a year ranges from 4.5% to 5.2%, which increases to 32.2% to 36% for veterans with a CAN score of 95. The probability range widens significantly (32.2%-93.1%) for patients in the top 5 CAN scores (95-99).

CAN scores are a potential screening tool for frailty among older adults; they are generated automatically and provide acceptable diagnostic accuracy. Hence, the CAN score may be a useful tool for primary care practitioners for the detection of frailty in their patients. The CAN score has shown a moderate positive association with the FRAIL Scale.^9,10 The population-based studies that have used the FI approach (differing FIs, depending on the data available) give robust results: People accumulate an average of 0.03 deficits per year after the age of 70 years.¹¹ Interventions to delay or reverse frailty have not been clearly defined with heterogeneity in the definition of frailty and measurement of frailty outcomes.^12,13 The prevalence of frailty in the veteran population is substantially higher than the prevalence in community populations with a similar age distribution. There is also mounting evidence that veterans accumulate deficits more rapidly than their civilian counterparts.¹⁴

COVID-19 was declared a pandemic in March 2020 and had many impacts on global health that were most marked in the first year. These included reductions in hospital visits for non-COVID-19 health concerns, a reduction in completed screening tests, an initial reduction in other infectious diseases (attributable to quarantines), and an increase or worsening of mental health concerns.^15,16

We aimed to investigate whether frailty increased disproportionately in a subset of older veterans in the first year of the COVID-19 pandemic when compared with the previous year using CAN scores. This single institution, longitudinal cohort study was determined to be exempt from institutional review board review but was approved by the Phoenix VA Health Care System (PVAHCS) Research and Development Committee.

Methods

The Office of Clinical Systems Development and Evaluation (CSDE–10E2A) produces a weekly CAN Score Report to help identify the highest-risk patients in a primary care panel or cohort. CAN scores range from 0 (lowest risk) to 99 (highest risk), indicating how likely a patient is to experience hospitalization or death compared with other VA patients. CAN scores are calculated with statistical prediction models that use data elements from the following Corporate Data Warehouse (CDW) domains: demographics, health care utilization, laboratory tests, medical conditions, medications, and vital signs (eAppendix available online at 10.12788/fp.0385).

The CAN Score Report is generated weekly and stored on a CDW server. A patient will receive all 6 distinct CAN scores if they are: (1) assigned to a primary care PACT on the risk date; (2) a veteran; (3) not hospitalized in a VA facility on the risk date; and (4) alive as of the risk date. New to CAN 2.5 is that patients who meet criteria 1, 2, and 4 but are hospitalized in a VA facility on the risk date will receive CAN scores for the 1-year and 90-day mortality models.

Utilizing VA Informatics and Computing Infrastructure (VA HSR RES 13-457, US Department of Veterans Affairs [2008]), we obtained 2 lists of veterans aged 70 to 75 years on February 8, 2019, with a calculated CAN score of ≥ 75 for 1-year mortality and 1-year hospitalization on that date. A veteran with a CAN score of ≥ 75 is likely to be prefrail or frail.^9,10 Veterans who did not have a corresponding calculated CAN score on February 7, 2020, and February 12, 2021, were excluded. COVID-19 was declared a public health emergency in the United States on January 31, 2020, and the World Health Organization declared COVID-19 a pandemic on March 11, 2020.¹⁷ We picked February 7, 2020, within this time frame and without any other special significance. We picked additional CAN score calculation dates approximately 1 year prior and 1 year after this date. Veterans had to be alive on February 12, 2021, (the last date of the CAN score) to be included in the cohorts.

Statistical Analyses

The difference in CAN score from one year to the next was calculated for each patient. The difference between 2019 and 2020 was compared with the difference between 2020 to 2021 using a paired t test. Yearly CAN score values were analyzed using repeated measures analysis of variance. The number of patients that showed an increase in CAN score (ie, increased risk of either mortality or hospitalization within the year) or a decrease (lower risk) was compared using the χ² test. IBM SPSS v26 and GraphPad Prism v18 were used for statistical analysis. P < .05 was considered statistically significant.

Results

There were 3538 veterans at PVAHCS who met the inclusion criteria and had a 1-year mortality CAN score ≥ 75 on February 8, 2019.

In the hospitalization group, there were 6046 veterans in the analysis; 57 veterans missing a 1-year hospitalization CAN score that were excluded. The mean age was 71.7 (1.3) years and included 5874 male (97.2%) and 172 female (2.8%) veterans. There was a decline in mean 1-year hospitalization CAN scores in our subset of frail older veterans by 2.8 (95% CI, -3.1 to -2.6) in the year preceding the COVID-19 pandemic. This mean decline slowed significantly to 1.5 (95% CI, -1.8 to -1.2; P < .0001) after the first year of the COVID-19 pandemic. Mean CAN scores for 1-year hospitalization were 84.6 (95% CI, 84.4 to 84.8), 81.8 (95% CI, 81.5 to 82.1), and 80.2 (95% CI, 79.9 to 80.6) for 2019, 2020, and 2021, respectively.

We also calculated the number of veterans with increasing, stable, and decreasing CAN scores across each of our defined periods in both the 1-year mortality and hospitalization groups.

Discussion

We studied frailty trends in an older veteran subpopulation enrolled at the PVAHCS 1 year prior and into the COVID-19 pandemic using CAN scores. Frailty is a dynamic state. Previous frailty assessments aimed to identify patients at the highest risk of death. With the advent of advanced therapeutics for several diseases, the number of medical conditions that are now managed as chronic illnesses continues to grow. There is a role for repeated measures of frailty to try to identify frailty trends.¹⁹ These trends may assist us in resource allocation, identifying interventions that work and those that do not.

Some studies have shown an overall declining lethality of frailty. This may reflect improvements in the care and management of chronic conditions, screening tests, and increased awareness of healthy lifestyles.²⁰ Another study of frailty trajectories in a veteran population in the 5 years preceding death showed multiple trajectories (stable, gradually increasing, rapidly increasing, and recovering).¹⁹

The PACT is a primary care model implemented at VA medical centers in April 2010. It is a patient-centered medical home model (PCMH) with several components. The VA treats a population of socioeconomically vulnerable patients with complex chronic illness management needs. Some of the components of a PACT model relevant to our study include facilitated self-management support for veterans in between practitioner visits via care partners, peer-to-peer and transitional care programs, physical activity and diet programs, primary care mental health, integration between primary and specialty care, and telehealth.²¹ A previous study has shown that VA primary care clinics with the most PCMH components in place had greater improvements in several chronic disease quality measures than in clinics with a lower number of PCMH components.²²

Limitations

Our study is limited by our older veteran population demographics. We chose only a subset of older veterans at a single VA center for this study and cannot extrapolate the results to all older frail veterans or community dwelling older adults. Robust individuals may also transition to prefrailty and frailty over longer periods; our study monitored frailty trends over 2 years.

CAN scores are not quality measures to improve upon. Allocation and utilization of additional resources may clinically benefit a patient but increase their CAN scores. Although our results are statistically significant, we are unable to make any conclusions about clinical significance.

Conclusions

Our study results indicate frailty as determined by 1-year mortality CAN scores significantly increased in a subset of older veterans during the first year of the COVID-19 pandemic when compared with the previous year. Whether this change in frailty is temporary or long lasting remains to be seen. Automated CAN scores can be effectively utilized to monitor frailty trends in certain veteran populations over longer periods.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Phoenix Veterans Affairs Health Care System.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

Pyogenic hepatic abscess (PHA) is a collection of pus in the liver caused by bacterial infection of the liver parenchyma. This potentially life-threatening condition has a mortality rate reported to be as high as 47%.¹ The incidence of PHA is reported to be 2.3 per 100,000 individuals and is more common in immunosuppressed individuals and those with diabetes mellitus, cancer, and liver transplant.^2,3 PHA infections are usually polymicrobial and most commonly include enteric organisms like Escherichia coli and Klebsiella pneumoniae.⁴

We present a rare cause of PHA with Fusobacterium nucleatum (F nucleatum) in an immunocompetent patient with poor oral health, history of diverticulitis, and recent COVID-19 infection whose only symptoms were chest pain and a 4-week history of fever and malaise.

Case Presentation

A 52-year-old man initially presented to the C.W. Bill Young Veterans Affairs Medical Center (CWBYVAMC) emergency department in Bay Pines, Florida, for fever, malaise, and right-sided chest pain on inspiration. The fever and malaise began while he was on vacation 4 weeks prior. He originally presented to an outside hospital where he tested positive for COVID-19 and was recommended ibuprofen and rest. His symptoms did not improve, and he returned a second time to the outside hospital 2 weeks later and was diagnosed with pneumonia and placed on outpatient antibiotics. The patient subsequently returned to CWBYVAMC 2 weeks after starting antibiotics when he began to develop right-sided inspiratory chest pain. He reported no other recent travel and no abdominal pain. The patient’s history was significant for diverticulitis 2 years before. A colonoscopy was performed during that time and showed no masses.

On presentation, the patient was febrile with a temperature of 100.8 °F; otherwise, his vital signs were stable. Physical examinations, including abdominal, respiratory, and cardiovascular, were unremarkable. The initial laboratory workup revealed a white blood cell (WBC) count of 18.7 K/μL (reference range, 5-10 K/μL) and microcytic anemia with a hemoglobin level of 8.8 g/dL. The comprehensive metabolic panel revealed normal aspartate transaminase, alanine transaminase, and total bilirubin levels and elevated alkaline phosphatase of 215 U/L (reference range, 44-147 U/L), revealing possible mild intrahepatic cholestasis. Urinalysis showed trace proteinuria and urobilinogen. Coagulation studies showed elevated D-dimer and procalcitonin levels at 1.9 ng/mL (reference range, < 0.1 ng/mL) and 1.21 ng/mL (reference range, < 0.5 ng/mL), respectively, with normal prothrombin and partial thromboplastin times. The patient had a normal troponin, fecal, and blood culture; entamoeba serology was negative.

A computed tomograph (CT) angiography of the chest was performed to rule out pulmonary embolism, revealing liver lesions suspicious for abscess or metastatic disease. Minimal pleural effusion was detected bilaterally. A subsequent CT confirmed the presence of hepatic lesions consistent with an abscess (Figure 1).

Discussion

F nucleatum is a gram-negative, nonmotile, spindle-shaped rod found in dental plaques.⁵ The incidence of F nucleatum bacteremia is 0.34 per 100,000 people and increases with age, with the median age being 53.5 years.⁶ Although our patient did not present with F nucleatum bacteremia, it is possible that bacteremia was present before hospitalization but resolved by the time the sample was drawn for culture. F nucleatum bacteremia can lead to a variety of presentations. The most common primary diagnoses are intra-abdominal infections (eg, PHA, respiratory tract infections, and hematological disorders).^1,6

PHA Presentation

The most common presenting symptoms of PHA are fever (88%), abdominal pain (79%), and vomiting (50%).⁴ The patient’s presentation of inspiratory right-sided chest pain is likely due to irritation of the diaphragmatic pleura of the right lung secondary to the abscess formation. The patient did not experience abdominal pain throughout the course of this disease or on palpation of his right upper quadrant. To our knowledge, this is the only case of PHA in the literature of a patient with inspiratory chest pain without respiratory infection, abdominal pain, and cardiac abnormalities. There was no radiologic evidence or signs of hypoxia on admission to CWBYVAMC, which makes respiratory infection an unlikely cause of the chest pain. Moreover, the patient presented with new-onset chest pain 2 weeks after the diagnosis of pneumonia.

Common laboratory findings of PHA include transaminitis, leukocytosis, and bilirubinemia.⁴ Of note, increased procalcitonin has also been associated with PHA and extreme elevation (> 200 μg/L) may be a useful biomarker to identify F nucleatum infections before the presence of leukocytosis.³ CT of PHA usually reveals right lobe involvement, and F nucleatum infection usually demonstrates multiple abscesses.^4,7

Contributing Factors in F nucleatum PHA

F nucleatum is associated with several oral diseases, such as periodontitis and gingivitis.⁸ It is important to do an oral inspection on patients with F nucleatum infections because it can spread from oral cavities to different body parts.

F nucleatum is also found in the gut.⁹ Any disease that can cause a break in the gastrointestinal mucosa may result in F nucleatum bacteremia and PHA. This may be why F nucleatum has been associated with a variety of different diseases, such as diverticulitis, inflammatory bowel disease, appendicitis, and colorectal cancer.^10,11 Our patient had a history of diverticulosis with diverticulitis. Bawa and colleagues described a patient with recurrent diverticulitis who developed F nucleatum bacteremia and PHA.¹¹ Our patient did not have any signs of diverticulitis.

Our patient’s COVID-19 infection also had a role in delaying the appropriate treatment of PHA. Without any symptoms of PHA, a diagnosis is difficult in a patient with a positive COVID-19 test, and treatment was delayed 1 month. Moreover, COVID-19 has been reported to delay the diagnosis of PHA even in the absence of a positive COVID-19 test. Collins and Diamond presented a patient during the COVID-19 pandemic who developed a periodontal abscess, which resulted in F nucleatum bacteremia and PHA due to delayed hospital presentation after the patient’s practitioners recommended self-isolation, despite a negative COVID-19 test.¹² This highlights the impact that COVID-19 may have on the timely diagnosis and treatment of patients with PHA.

Malignancy has been associated with F nucleatum bacteremia.^1,13 Possibly the association is due to gastrointestinal mucosa malignancy’s ability to cause micro-abrasions, resulting in F nucleatum bacteremia.¹⁰ Additionally, F nucleatum may promote the development of colorectal neoplasms.⁸ Due to this association, screening for colorectal cancer in patients with F nucleatum infection is important. In our patient, a colonoscopy was performed during the patient’s hospitalization for diverticulitis 2 years prior. No signs of colorectal neoplasm were noted

Conclusions

PHA due to F nucleatum is a rare but potentially life-threatening condition that must be diagnosed and treated promptly. It usually presents with fever, abdominal pain, and vomiting but can present with chest pain in the absence of a respiratory infection, cardiac abnormalities, and abdominal pain, as in our patient. A wide spectrum of infections can occur with F nucleatum, including PHA.

Suspicion for infection with this organism should be kept high in middle-aged and older individuals who present with an indolent disease course and have risk factors, such as poor oral health and comorbidities. Suspicion should be kept high even in the event of COVID-19 infection, especially in individuals with prolonged fever without other signs indicating respiratory infection. We believe that the most likely causes of this patient’s infection were his dental caries and periodontal disease. The timing of his symptoms is not consistent with his previous episode of diverticulitis. Due to the mortality of PHA, diagnosis and treatment must be prompt. Initial treatment with drainage and empiric anaerobic coverage is recommended, followed by a tailored antibiotic regiment if indicated by culture, and further drainage if suggested by imaging.

The US Coast Guard (USCG) operates within the US Department of Homeland Security during times of peace and represents a force of > 55,000 active-duty service members (ADSMs), civilians, and reservists. ADSMs account for about 40,000 USCG personnel. The missions of the USCG include activities such as maritime law enforcement (drug interdiction), search and rescue, and defense readiness.¹ Akin to other US Department of Defense (DoD) services, USCG ADSMs are required to maintain medical readiness to maximize operational success.

Whereas the DoD centralizes its health care services at military treatment facilities, USCG health care tends to be dispersed to smaller clinics and sickbays across large geographic areas. The USCG operates 42 clinics of varying sizes and medical capabilities, providing outpatient, dentistry, pharmacy, laboratory, radiology, physical therapy, optometry, and other health care services. Many ADSMs are evaluated by a USCG medical officer in these outpatient clinics, and ADSMs may choose to fill prescriptions at the in-house pharmacy if present at that clinic.

The USCG has 14 field pharmacists. In addition to the standard dispensing role at their respective clinics, USCG pharmacists provide regional oversight of pharmaceutical services for USCG units within their area of responsibility (AOR). Therefore, USCG pharmacists clinically, operationally, and logistically support these regional assets within their AOR while serving the traditional pharmacist role. USCG pharmacists have access to ADSM electronic health records (EHRs) when evaluating prescription orders, similar to other ambulatory care settings.

New recruits and accessions into the USCG are first screened for disqualifying health conditions, and ADSMs are required to maintain medical readiness throughout their careers.² Therefore, this population tends to be younger and overall healthier compared with the general population. Equally important, medication errors or inappropriate prescribing in the ADSM group could negatively affect their duty status and mission readiness of the USCG in addition to exposing the ADSM to medication-related harms.

Duty status is an important and unique consideration in this population. ADSMs are expected to be deployable worldwide and physically and mentally capable of executing all duties associated with their position. Duty status implications and the perceived ability to stand watch are tied to an ADMS’s specialty, training, and unit role. Duty status is based on various frameworks like the USCG Medical Manual, Aeromedical Policy Letters, and other governing documents.³ Duty status determinations are initiated by privileged USCG medical practitioners and may be executed in consultation with relevant commands and other subject matter experts. An inappropriately dosed antibiotic prescription, for example, can extend the duration that an ADSM would be considered unfit for full duty due to prolonged illness. Accordingly, being on a limited duty status may negatively affect USCG total mission readiness as a whole. USCG pharmacists play a vital role in optimizing ADSMs’ medication therapies to ensure safety and efficacy.

Currently no published literature explores the number of medication interventions or the impact of those interventions made by USCG pharmacists. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic over 6 months.

Methods

As part of a USCG quality improvement study, a pharmacist tracked all medication interventions on a spreadsheet at USCG Base Alameda clinic from July 1, 2021, to December 31, 2021. The study defined a medication intervention as a communication with the prescriber with the intention to change the medication, strength, dose, dosage form, quantity, or instructions. Each intervention was subcategorized as either a drug therapy problem (DTP) or a non-DTP intervention. Interventions were divided into 7 categories.

Each DTP intervention was evaluated in a retrospective chart review by a panel of USCG pharmacists to assess for duty status severity and replicability. For duty status severity, the panel reviewed the intervention after considering patient-specific factors and determined whether the original prescribing (had there not been an intervention) could have reasonably resulted in a change of duty status for the ADSM from a fit for full duty (FFFD) status to a different duty status (eg, fit for limited duty [FFLD]). This duty status review factored in potential impacts across multiple positions and billets, including aviators (pilots) and divers. In addition, the panel, whose members all have prior community pharmacy experience, assessed replicability by determining whether the same intervention could have reasonably been made in the absence of access to the patient EHR, as would be common in a community pharmacy setting.

Interventions without an identified DTP were considered non-DTP interventions. These interventions involved recommendations for a more cost-effective medication or a similar in stock therapeutic option to minimize delay of patient care. The spreadsheet also included the date, medication name, medication class, specific intervention made, outcome, and other descriptive comments.

Results

During the 6-month period, 1751 prescriptions were dispensed at USCG Base Alameda pharmacy with 116 interventions (7%).

Among the DTP interventions, 26 (41%) dealt with an inappropriate dose, 13 (20%) were for medication omission, 7 (11%) for inappropriate dosage form, and 6 (9%) for excess medication (Table 2).

Discussion

This study is novel in examining the impact of a pharmacist’s medication interventions in a USCG ambulatory care practice setting. A PubMed literature search of the phrases “Coast Guard AND pharmacy” or “Coast Guard AND pharmacy AND intervention” yielded no results specific to pharmacy interventions in a USCG setting. However, the 2021 implementation of the enterprise-wide MHS GENESIS EHR may support additional tracking and analysis tools in the future.

Pharmacist interventions have been studied in diverse patient populations and practice settings, and most conclude that pharmacists make meaningful interventions at their respective organizations.^4-7 Many of these studies were conducted at open-door health care systems, whereas USCG clinics serve ADSMs nearly exclusively. The ADSM population tends to be younger and healthier due to age requirements and medical accession and retention standards.

It is important to recognize the value of a USCG pharmacist in identifying and rectifying potential medication errors, particularly those that may affect the ability to stand duty for ADSMs. An example intervention includes changing the daily starting dose of citalopram from the ordered 30 mg to the intended 10 mg. Inappropriately prescribed medication regimens may increase the incidence of adverse effects or prolong duration to therapeutic efficacy, which impairs the ability to stand duty. There were 3 circumstances where the prescriber had ordered the medication for an incorrect ADSM that were rectified by the pharmacist. If left unchanged, these errors could negatively affect the ADSM’s overall health, well-being, and duty status.

The acceptance rate for interventions in this study was 96%. The literature suggests a highly variable acceptance rate of pharmacist interventions when examined across various practice settings, health systems, and geographic locations.^8-10 This study’s comparatively high rate could be due to the pharmacist-prescriber relationships at USCG clinics. By virtue of colocatation and teamwork initiatives, the pharmacist has the opportunity to develop positive rapport with physicians, physician assistants, and other clinic staff.

Having access to EHRs allowed the pharmacist to make 18 of the DTP interventions. Chart access is not unique to the USCG and is common in other ambulatory care settings. Those 18 interventions, such as reconciling a prescription ordered as fluticasone/salmeterol but recorded in the EHR as “will prescribe montelukast,” were deemed possible because of EHR access. Such interventions could potentially be lost if ADSMs solely received their pharmaceutical care elsewhere.

USCG uses independent duty health services technicians (IDHSs) who practice in settings where a medical officer is not present, such as at smaller sickbays or aboard Coast Guard cutters. In this study, an IDHS had mistakenly created a medication order for the medical officer to sign for bupropion SR, when the ADSM had been taking and was intended to continue taking bupropion XL. This order was signed off by the medical officer, but this oversight was identified and corrected by the pharmacist before dispensing. This indicates that there is a vital educational role that the USCG pharmacist fulfills when working with health care team members within the AOR.

Equally important to consider are the non-DTP interventions. In a military setting, minimizations of delay in care are a high priority. There were 34 instances where the pharmacist made an intervention to recommend a similar therapeutic medication that was in stock to ensure that the ADSM had timely access to the medication without the need for prior authorization. In the context of short-notice, mission-critical deployments that may last for multiple months, recognizing medication shortages or other inventory constraints and recommending therapeutic alternatives ensures that the USCG can maintain a ready posture for missions in addition to providing timely and quality patient care.

Saving about $1700 over 6 months is also important. While this was not explicitly evaluated in the study, prescribers may not be acutely aware of medication pricing. There are often significant price differences between different formulations of the same medication (eg, naproxen delayed-release vs tablets). Because USCG pharmacists are responsible for ordering medications and managing their regional budget within the AOR, they are best poised to make cost-savings recommendations. These interventions suggest that USCG pharmacists must continue to remain actively involved in the patient care team alongside physicians, physician assistants, nurses, and corpsmen. Throughout this setting and in so many others, patients’ health outcomes improve when pharmacists are more engaged in the pharmacotherapy care plan.

Limitations

Currently, the USCG does not publish ADSM demographic or health-related data, making it difficult to evaluate these interventions in the context of age, gender, or type of disease. Accordingly, potential directions for future research include how USCG pharmacists’ interventions are stratified by duty station and initial diagnosis. Such studies may support future models where USCG pharmacists are providing targeted education to prescribers based on disease or medication classes.

This analysis may have limited applicability to other practice settings even within USCG. Most USCG clinics have a limited number of medical officers; indeed, many have only one, and clinics with pharmacies typically have 1 to 5 medical officers aboard. USCG medical officers have a multitude of other duties, which may impact prescribing patterns and pharmacist interventions. Statistical analyses were limited by the dearth of baseline data or comparative literature. Finally, the assessment of DTP interventions’ impact did not use an official measurement tool like the US Department of Veterans Affairs’ Safety Assessment Code matrix.¹¹ Instead, the study used the internal USCG pharmacist panel for the fitness for duty consideration as the main stratification of the DTP interventions’ duty status severity, because maintaining medical readiness is the top priority for a USCG clinic.

Conclusions

The multifaceted role of pharmacists in USCG clinics includes collaborating with the patient care team to make pharmacy interventions that have significant impacts on ADSMs’ wellness and the USCG mission. The ADSMs of this nation deserve quality medical care that translates into mission readiness, and the USCG pharmacy force stands ready to support that goal.

Acknowledgments

The authors acknowledge the contributions of CDR Christopher Janik, US Coast Guard Headquarters, and LCDR Darin Schneider, US Coast Guard D11 Regional Practice Manager, in the drafting of the manuscript.

The US Coast Guard (USCG) operates within the US Department of Homeland Security during times of peace and represents a force of > 55,000 active-duty service members (ADSMs), civilians, and reservists. ADSMs account for about 40,000 USCG personnel. The missions of the USCG include activities such as maritime law enforcement (drug interdiction), search and rescue, and defense readiness.¹ Akin to other US Department of Defense (DoD) services, USCG ADSMs are required to maintain medical readiness to maximize operational success.

Whereas the DoD centralizes its health care services at military treatment facilities, USCG health care tends to be dispersed to smaller clinics and sickbays across large geographic areas. The USCG operates 42 clinics of varying sizes and medical capabilities, providing outpatient, dentistry, pharmacy, laboratory, radiology, physical therapy, optometry, and other health care services. Many ADSMs are evaluated by a USCG medical officer in these outpatient clinics, and ADSMs may choose to fill prescriptions at the in-house pharmacy if present at that clinic.

The USCG has 14 field pharmacists. In addition to the standard dispensing role at their respective clinics, USCG pharmacists provide regional oversight of pharmaceutical services for USCG units within their area of responsibility (AOR). Therefore, USCG pharmacists clinically, operationally, and logistically support these regional assets within their AOR while serving the traditional pharmacist role. USCG pharmacists have access to ADSM electronic health records (EHRs) when evaluating prescription orders, similar to other ambulatory care settings.

New recruits and accessions into the USCG are first screened for disqualifying health conditions, and ADSMs are required to maintain medical readiness throughout their careers.² Therefore, this population tends to be younger and overall healthier compared with the general population. Equally important, medication errors or inappropriate prescribing in the ADSM group could negatively affect their duty status and mission readiness of the USCG in addition to exposing the ADSM to medication-related harms.

Duty status is an important and unique consideration in this population. ADSMs are expected to be deployable worldwide and physically and mentally capable of executing all duties associated with their position. Duty status implications and the perceived ability to stand watch are tied to an ADMS’s specialty, training, and unit role. Duty status is based on various frameworks like the USCG Medical Manual, Aeromedical Policy Letters, and other governing documents.³ Duty status determinations are initiated by privileged USCG medical practitioners and may be executed in consultation with relevant commands and other subject matter experts. An inappropriately dosed antibiotic prescription, for example, can extend the duration that an ADSM would be considered unfit for full duty due to prolonged illness. Accordingly, being on a limited duty status may negatively affect USCG total mission readiness as a whole. USCG pharmacists play a vital role in optimizing ADSMs’ medication therapies to ensure safety and efficacy.

Currently no published literature explores the number of medication interventions or the impact of those interventions made by USCG pharmacists. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic over 6 months.

Methods

As part of a USCG quality improvement study, a pharmacist tracked all medication interventions on a spreadsheet at USCG Base Alameda clinic from July 1, 2021, to December 31, 2021. The study defined a medication intervention as a communication with the prescriber with the intention to change the medication, strength, dose, dosage form, quantity, or instructions. Each intervention was subcategorized as either a drug therapy problem (DTP) or a non-DTP intervention. Interventions were divided into 7 categories.

Each DTP intervention was evaluated in a retrospective chart review by a panel of USCG pharmacists to assess for duty status severity and replicability. For duty status severity, the panel reviewed the intervention after considering patient-specific factors and determined whether the original prescribing (had there not been an intervention) could have reasonably resulted in a change of duty status for the ADSM from a fit for full duty (FFFD) status to a different duty status (eg, fit for limited duty [FFLD]). This duty status review factored in potential impacts across multiple positions and billets, including aviators (pilots) and divers. In addition, the panel, whose members all have prior community pharmacy experience, assessed replicability by determining whether the same intervention could have reasonably been made in the absence of access to the patient EHR, as would be common in a community pharmacy setting.

Interventions without an identified DTP were considered non-DTP interventions. These interventions involved recommendations for a more cost-effective medication or a similar in stock therapeutic option to minimize delay of patient care. The spreadsheet also included the date, medication name, medication class, specific intervention made, outcome, and other descriptive comments.

Results

During the 6-month period, 1751 prescriptions were dispensed at USCG Base Alameda pharmacy with 116 interventions (7%).

Among the DTP interventions, 26 (41%) dealt with an inappropriate dose, 13 (20%) were for medication omission, 7 (11%) for inappropriate dosage form, and 6 (9%) for excess medication (Table 2).

Discussion

This study is novel in examining the impact of a pharmacist’s medication interventions in a USCG ambulatory care practice setting. A PubMed literature search of the phrases “Coast Guard AND pharmacy” or “Coast Guard AND pharmacy AND intervention” yielded no results specific to pharmacy interventions in a USCG setting. However, the 2021 implementation of the enterprise-wide MHS GENESIS EHR may support additional tracking and analysis tools in the future.

Pharmacist interventions have been studied in diverse patient populations and practice settings, and most conclude that pharmacists make meaningful interventions at their respective organizations.^4-7 Many of these studies were conducted at open-door health care systems, whereas USCG clinics serve ADSMs nearly exclusively. The ADSM population tends to be younger and healthier due to age requirements and medical accession and retention standards.

It is important to recognize the value of a USCG pharmacist in identifying and rectifying potential medication errors, particularly those that may affect the ability to stand duty for ADSMs. An example intervention includes changing the daily starting dose of citalopram from the ordered 30 mg to the intended 10 mg. Inappropriately prescribed medication regimens may increase the incidence of adverse effects or prolong duration to therapeutic efficacy, which impairs the ability to stand duty. There were 3 circumstances where the prescriber had ordered the medication for an incorrect ADSM that were rectified by the pharmacist. If left unchanged, these errors could negatively affect the ADSM’s overall health, well-being, and duty status.

The acceptance rate for interventions in this study was 96%. The literature suggests a highly variable acceptance rate of pharmacist interventions when examined across various practice settings, health systems, and geographic locations.^8-10 This study’s comparatively high rate could be due to the pharmacist-prescriber relationships at USCG clinics. By virtue of colocatation and teamwork initiatives, the pharmacist has the opportunity to develop positive rapport with physicians, physician assistants, and other clinic staff.

Having access to EHRs allowed the pharmacist to make 18 of the DTP interventions. Chart access is not unique to the USCG and is common in other ambulatory care settings. Those 18 interventions, such as reconciling a prescription ordered as fluticasone/salmeterol but recorded in the EHR as “will prescribe montelukast,” were deemed possible because of EHR access. Such interventions could potentially be lost if ADSMs solely received their pharmaceutical care elsewhere.

USCG uses independent duty health services technicians (IDHSs) who practice in settings where a medical officer is not present, such as at smaller sickbays or aboard Coast Guard cutters. In this study, an IDHS had mistakenly created a medication order for the medical officer to sign for bupropion SR, when the ADSM had been taking and was intended to continue taking bupropion XL. This order was signed off by the medical officer, but this oversight was identified and corrected by the pharmacist before dispensing. This indicates that there is a vital educational role that the USCG pharmacist fulfills when working with health care team members within the AOR.

Equally important to consider are the non-DTP interventions. In a military setting, minimizations of delay in care are a high priority. There were 34 instances where the pharmacist made an intervention to recommend a similar therapeutic medication that was in stock to ensure that the ADSM had timely access to the medication without the need for prior authorization. In the context of short-notice, mission-critical deployments that may last for multiple months, recognizing medication shortages or other inventory constraints and recommending therapeutic alternatives ensures that the USCG can maintain a ready posture for missions in addition to providing timely and quality patient care.

Saving about $1700 over 6 months is also important. While this was not explicitly evaluated in the study, prescribers may not be acutely aware of medication pricing. There are often significant price differences between different formulations of the same medication (eg, naproxen delayed-release vs tablets). Because USCG pharmacists are responsible for ordering medications and managing their regional budget within the AOR, they are best poised to make cost-savings recommendations. These interventions suggest that USCG pharmacists must continue to remain actively involved in the patient care team alongside physicians, physician assistants, nurses, and corpsmen. Throughout this setting and in so many others, patients’ health outcomes improve when pharmacists are more engaged in the pharmacotherapy care plan.

Limitations

Currently, the USCG does not publish ADSM demographic or health-related data, making it difficult to evaluate these interventions in the context of age, gender, or type of disease. Accordingly, potential directions for future research include how USCG pharmacists’ interventions are stratified by duty station and initial diagnosis. Such studies may support future models where USCG pharmacists are providing targeted education to prescribers based on disease or medication classes.

This analysis may have limited applicability to other practice settings even within USCG. Most USCG clinics have a limited number of medical officers; indeed, many have only one, and clinics with pharmacies typically have 1 to 5 medical officers aboard. USCG medical officers have a multitude of other duties, which may impact prescribing patterns and pharmacist interventions. Statistical analyses were limited by the dearth of baseline data or comparative literature. Finally, the assessment of DTP interventions’ impact did not use an official measurement tool like the US Department of Veterans Affairs’ Safety Assessment Code matrix.¹¹ Instead, the study used the internal USCG pharmacist panel for the fitness for duty consideration as the main stratification of the DTP interventions’ duty status severity, because maintaining medical readiness is the top priority for a USCG clinic.

Conclusions

The multifaceted role of pharmacists in USCG clinics includes collaborating with the patient care team to make pharmacy interventions that have significant impacts on ADSMs’ wellness and the USCG mission. The ADSMs of this nation deserve quality medical care that translates into mission readiness, and the USCG pharmacy force stands ready to support that goal.

Acknowledgments

The authors acknowledge the contributions of CDR Christopher Janik, US Coast Guard Headquarters, and LCDR Darin Schneider, US Coast Guard D11 Regional Practice Manager, in the drafting of the manuscript.

The US Coast Guard (USCG) operates within the US Department of Homeland Security during times of peace and represents a force of > 55,000 active-duty service members (ADSMs), civilians, and reservists. ADSMs account for about 40,000 USCG personnel. The missions of the USCG include activities such as maritime law enforcement (drug interdiction), search and rescue, and defense readiness.¹ Akin to other US Department of Defense (DoD) services, USCG ADSMs are required to maintain medical readiness to maximize operational success.

Whereas the DoD centralizes its health care services at military treatment facilities, USCG health care tends to be dispersed to smaller clinics and sickbays across large geographic areas. The USCG operates 42 clinics of varying sizes and medical capabilities, providing outpatient, dentistry, pharmacy, laboratory, radiology, physical therapy, optometry, and other health care services. Many ADSMs are evaluated by a USCG medical officer in these outpatient clinics, and ADSMs may choose to fill prescriptions at the in-house pharmacy if present at that clinic.

The USCG has 14 field pharmacists. In addition to the standard dispensing role at their respective clinics, USCG pharmacists provide regional oversight of pharmaceutical services for USCG units within their area of responsibility (AOR). Therefore, USCG pharmacists clinically, operationally, and logistically support these regional assets within their AOR while serving the traditional pharmacist role. USCG pharmacists have access to ADSM electronic health records (EHRs) when evaluating prescription orders, similar to other ambulatory care settings.

New recruits and accessions into the USCG are first screened for disqualifying health conditions, and ADSMs are required to maintain medical readiness throughout their careers.² Therefore, this population tends to be younger and overall healthier compared with the general population. Equally important, medication errors or inappropriate prescribing in the ADSM group could negatively affect their duty status and mission readiness of the USCG in addition to exposing the ADSM to medication-related harms.

Duty status is an important and unique consideration in this population. ADSMs are expected to be deployable worldwide and physically and mentally capable of executing all duties associated with their position. Duty status implications and the perceived ability to stand watch are tied to an ADMS’s specialty, training, and unit role. Duty status is based on various frameworks like the USCG Medical Manual, Aeromedical Policy Letters, and other governing documents.³ Duty status determinations are initiated by privileged USCG medical practitioners and may be executed in consultation with relevant commands and other subject matter experts. An inappropriately dosed antibiotic prescription, for example, can extend the duration that an ADSM would be considered unfit for full duty due to prolonged illness. Accordingly, being on a limited duty status may negatively affect USCG total mission readiness as a whole. USCG pharmacists play a vital role in optimizing ADSMs’ medication therapies to ensure safety and efficacy.

Currently no published literature explores the number of medication interventions or the impact of those interventions made by USCG pharmacists. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic over 6 months.

Methods

As part of a USCG quality improvement study, a pharmacist tracked all medication interventions on a spreadsheet at USCG Base Alameda clinic from July 1, 2021, to December 31, 2021. The study defined a medication intervention as a communication with the prescriber with the intention to change the medication, strength, dose, dosage form, quantity, or instructions. Each intervention was subcategorized as either a drug therapy problem (DTP) or a non-DTP intervention. Interventions were divided into 7 categories.

Each DTP intervention was evaluated in a retrospective chart review by a panel of USCG pharmacists to assess for duty status severity and replicability. For duty status severity, the panel reviewed the intervention after considering patient-specific factors and determined whether the original prescribing (had there not been an intervention) could have reasonably resulted in a change of duty status for the ADSM from a fit for full duty (FFFD) status to a different duty status (eg, fit for limited duty [FFLD]). This duty status review factored in potential impacts across multiple positions and billets, including aviators (pilots) and divers. In addition, the panel, whose members all have prior community pharmacy experience, assessed replicability by determining whether the same intervention could have reasonably been made in the absence of access to the patient EHR, as would be common in a community pharmacy setting.

Interventions without an identified DTP were considered non-DTP interventions. These interventions involved recommendations for a more cost-effective medication or a similar in stock therapeutic option to minimize delay of patient care. The spreadsheet also included the date, medication name, medication class, specific intervention made, outcome, and other descriptive comments.

Results

During the 6-month period, 1751 prescriptions were dispensed at USCG Base Alameda pharmacy with 116 interventions (7%).

Among the DTP interventions, 26 (41%) dealt with an inappropriate dose, 13 (20%) were for medication omission, 7 (11%) for inappropriate dosage form, and 6 (9%) for excess medication (Table 2).

Discussion

This study is novel in examining the impact of a pharmacist’s medication interventions in a USCG ambulatory care practice setting. A PubMed literature search of the phrases “Coast Guard AND pharmacy” or “Coast Guard AND pharmacy AND intervention” yielded no results specific to pharmacy interventions in a USCG setting. However, the 2021 implementation of the enterprise-wide MHS GENESIS EHR may support additional tracking and analysis tools in the future.

Pharmacist interventions have been studied in diverse patient populations and practice settings, and most conclude that pharmacists make meaningful interventions at their respective organizations.^4-7 Many of these studies were conducted at open-door health care systems, whereas USCG clinics serve ADSMs nearly exclusively. The ADSM population tends to be younger and healthier due to age requirements and medical accession and retention standards.

It is important to recognize the value of a USCG pharmacist in identifying and rectifying potential medication errors, particularly those that may affect the ability to stand duty for ADSMs. An example intervention includes changing the daily starting dose of citalopram from the ordered 30 mg to the intended 10 mg. Inappropriately prescribed medication regimens may increase the incidence of adverse effects or prolong duration to therapeutic efficacy, which impairs the ability to stand duty. There were 3 circumstances where the prescriber had ordered the medication for an incorrect ADSM that were rectified by the pharmacist. If left unchanged, these errors could negatively affect the ADSM’s overall health, well-being, and duty status.

The acceptance rate for interventions in this study was 96%. The literature suggests a highly variable acceptance rate of pharmacist interventions when examined across various practice settings, health systems, and geographic locations.^8-10 This study’s comparatively high rate could be due to the pharmacist-prescriber relationships at USCG clinics. By virtue of colocatation and teamwork initiatives, the pharmacist has the opportunity to develop positive rapport with physicians, physician assistants, and other clinic staff.

Having access to EHRs allowed the pharmacist to make 18 of the DTP interventions. Chart access is not unique to the USCG and is common in other ambulatory care settings. Those 18 interventions, such as reconciling a prescription ordered as fluticasone/salmeterol but recorded in the EHR as “will prescribe montelukast,” were deemed possible because of EHR access. Such interventions could potentially be lost if ADSMs solely received their pharmaceutical care elsewhere.

USCG uses independent duty health services technicians (IDHSs) who practice in settings where a medical officer is not present, such as at smaller sickbays or aboard Coast Guard cutters. In this study, an IDHS had mistakenly created a medication order for the medical officer to sign for bupropion SR, when the ADSM had been taking and was intended to continue taking bupropion XL. This order was signed off by the medical officer, but this oversight was identified and corrected by the pharmacist before dispensing. This indicates that there is a vital educational role that the USCG pharmacist fulfills when working with health care team members within the AOR.

Equally important to consider are the non-DTP interventions. In a military setting, minimizations of delay in care are a high priority. There were 34 instances where the pharmacist made an intervention to recommend a similar therapeutic medication that was in stock to ensure that the ADSM had timely access to the medication without the need for prior authorization. In the context of short-notice, mission-critical deployments that may last for multiple months, recognizing medication shortages or other inventory constraints and recommending therapeutic alternatives ensures that the USCG can maintain a ready posture for missions in addition to providing timely and quality patient care.

Saving about $1700 over 6 months is also important. While this was not explicitly evaluated in the study, prescribers may not be acutely aware of medication pricing. There are often significant price differences between different formulations of the same medication (eg, naproxen delayed-release vs tablets). Because USCG pharmacists are responsible for ordering medications and managing their regional budget within the AOR, they are best poised to make cost-savings recommendations. These interventions suggest that USCG pharmacists must continue to remain actively involved in the patient care team alongside physicians, physician assistants, nurses, and corpsmen. Throughout this setting and in so many others, patients’ health outcomes improve when pharmacists are more engaged in the pharmacotherapy care plan.

Limitations

Currently, the USCG does not publish ADSM demographic or health-related data, making it difficult to evaluate these interventions in the context of age, gender, or type of disease. Accordingly, potential directions for future research include how USCG pharmacists’ interventions are stratified by duty station and initial diagnosis. Such studies may support future models where USCG pharmacists are providing targeted education to prescribers based on disease or medication classes.

This analysis may have limited applicability to other practice settings even within USCG. Most USCG clinics have a limited number of medical officers; indeed, many have only one, and clinics with pharmacies typically have 1 to 5 medical officers aboard. USCG medical officers have a multitude of other duties, which may impact prescribing patterns and pharmacist interventions. Statistical analyses were limited by the dearth of baseline data or comparative literature. Finally, the assessment of DTP interventions’ impact did not use an official measurement tool like the US Department of Veterans Affairs’ Safety Assessment Code matrix.¹¹ Instead, the study used the internal USCG pharmacist panel for the fitness for duty consideration as the main stratification of the DTP interventions’ duty status severity, because maintaining medical readiness is the top priority for a USCG clinic.

Conclusions

The multifaceted role of pharmacists in USCG clinics includes collaborating with the patient care team to make pharmacy interventions that have significant impacts on ADSMs’ wellness and the USCG mission. The ADSMs of this nation deserve quality medical care that translates into mission readiness, and the USCG pharmacy force stands ready to support that goal.

Acknowledgments

The authors acknowledge the contributions of CDR Christopher Janik, US Coast Guard Headquarters, and LCDR Darin Schneider, US Coast Guard D11 Regional Practice Manager, in the drafting of the manuscript.

Advances in technology, including ubiquitous access to the internet and the capacity to transfer high-resolution representative images, have facilitated the adoption of telepathology by laboratories worldwide.^1-5 Telepathology includes the use of telecommunication links that enable transmission of digital pathology images for primary diagnosis, quality assurance (QA), education, research, or second opinion diagnoses.³ This improvement has culminated in approvals by the US Food and Drug Administration (FDA) of whole slide imaging (WSI) systems for surgical pathology slides: specifically, the Philips IntelliSite Digital Pathology Solution in 2017 and the Leica Aperio AT2 DX in 2020.^6-8 However, the approvals do not include telecytology due to lack of whole slide multiplanar scanning at different planes of focus or z-stacking capabilities.⁷

Long-term trends in pathology, specifically the slow reduction in the number of practicing pathologists available in the workforce compared with the total served population, along with the social distancing imperatives and disruptions brought about by the COVID-19 pandemic have made telepathology implementation pertinent to continue and improve pathology practice.^8-10

Description and Definitions

The primary modes of telepathology (static image telepathology, robotic telepathology, video microscopy, WSI, and multimodality telepathology) have been defined by the American Telemedicine Association (ATA).² WSI has been particularly suited for telepathology due to the ability to view digital slides in high resolution at various magnifications. These image files can also be viewed and shared with ease with other observers. Also, they take a shorter time to view compared with the use of a robotic microscope.³

Selection, Validation, and Implementation

WSI platforms vary in their characteristics and have several parameters, including but not limited to batch scanning vs continuous or random-access processing, throughput volume capacities, scan speed, cost, manual vs automatic loading of slides, image quality, slide capacity, flexibility for different slide sizes/features, telepathology capabilities once slide scanned, z-stacking, and regulatory approval status.⁸ Selection of the WSI device is dependent on need and cost considerations. For example, use for frozen section requires faster scanning speed and does not generally require a high throughput scanner.

Validation of telepathology by the testing site demonstrates that the new system performs as expected for its intended clinical use before being put into service and that the digital slides produced are acceptable for clinical diagnostic interpretation.¹¹ The College of American Pathologists (CAP) established WSI validation guidelines are part of the published laboratory standard of care.^11-13 An appropriate validation enables the benefits of telepathology while mitigating the risks.

There are 3 major CAP recommendations for validation. First, ≥ 60 cases should be included for each use case being validated with 20 additional cases for relevant ancillary applications not included in the 60 cases. Second, diagnostic concordance (ideally ≥ 95%) should be established between digital and glass slides for the same observer. Third, there should be a 2-week washout period between the viewing of digital and glass slides (Table 2).^12,13

Guidelines from the ATA establish that telepathology systems should be validated for clinical use, including non-WSI platforms.² Published validations of other non-WSI platforms (such as by robotic or multimodality telepathology) have followed the structure proposed in the guidelines by CAP for validating WSI.^14,15

Ensuring that all relevant responsibilities (clinical, facility, technical, training, documentation/archiving, quality management, and operations related) for the use of telepathology are met is another aspect of validation and implementation.² Clinical responsibilities include an agreement between the sending (referring) and receiving (consulting) parties on the information to accompany the digital material.² From ATA clinical guidelines, this includes identification information, provision to the consulting pathologist of all relevant clinical data, provision to retrieve for access any needed and/or relevant diagnostic material, and responsibility by referrer that the correct image/metadata was sent.² Involved parties should be trained to manage the materials being transmitted.²

Facility responsibilities include maintaining the standard of care defined by the facility and regulatory agencies.² The maintenance of accreditation, adherence to licensure requirements, and proper management of privileges to practice telepathology are also important.² Technical responsibilities include ensuring a proper validation that meets the standard of care and covers use cases.^2,11-13

All processes, training, and competencies should be followed and documented per standard facility operating procedures.² ATA recommends that telepathology should result in a formal report for diagnostic consultations, maintain logs of telepathology interactions or disclaimer statements, and have an appropriate retention policy.² The CAP recommends digital images used for primary diagnosis should be kept for 10 years if the original glass slides are not available.¹⁶ Once implemented, telepathology reports must be incorporated into the pathology and laboratory medicine department’s quality management plan for both the technical performance of the telepathology system and diagnostic performance of the pathologists using the system.² Operations responsibilities include ensuring that the telepathology system is maintained according to vendor recommendations and regulatory standards. Appropriate provisions for space and associated needs should be developed in conjunction with the information technology team of the facility to ensure appropriate security, privacy, and regulatory compliance.²

Applications and Uses

Telecytology. Rapid real-time telecytology has been documented to be useful in rapid on-site evaluations (ROSE) of the adequacy of fine needle aspirations (FNA).^17-21 Nevertheless, current Medicare reimbursement is limited given that ROSE is cost prohibitive, time consuming, and affects productivity in cytology laboratories.^17,22,23 Estimates of the time to provide ROSE for 1 procedure without telecytology range from 48.7 to 56.2 minutes.^17,23 The use of telecytology significantly reduces pathologist ROSE time without losing quality to about 12 minutes, of which only an average of 7.5 minutes was spent by the cytopathologist for the ROSE diagnosis.^17-21 ROSE also can be used for distant and remote locations to improve patient care.^17-21 Multiple vendors provide real-time telecytology service. Innovations using smartphone adapters, digital cameras that could work as their own IP addresses, and connection with high-speed dedicated connections with viewing platforms on high-sensitivity monitors can facilitate ROSE to improve patient management.^24,25 The successful accurate use of ROSE has been described; however, there are currently no FDA-approved telepathology ROSE platforms.^17-19,21-25

To date, the FDA has not approved any telecytology whole slide scanner due to a lack of z-stacking capability in submitted scanners.^7,21 Not all whole slide scanners offer z-stacking, though even in those that do offer it, the time necessary to scan the entire slide with adequate z-stacking takes too long to be clinically acceptable for many situations involving ROSE.²¹ WSI has also been used to develop international consensus for cytologic samples.²⁶ Published recommendations for the validation of these other modalities before usage follow the spirit of the CAP guidelines (as far as multiple cases with high concordance rates) for validation of WSI for diagnostic purposes but vary on the exact number of slides and acceptable concordance rate.^21,27 For ROSE with a robotic microscope without any on-site cytology personnel, documented standardized training of nonpathology staff members, such as the radiologist or other physician performing the FNA procedure, may be needed to enable the performance of ROSE telecytology and ensure compliance with regulations.^2,21 Besides ROSE, there are published validations for telecytology in primary diagnosis and QA, indicating a role for telecytology for diagnosis for laboratories that have properly validated and implemented the laboratory-developed test.^28-30

Frozen section. Telepathology has significant potential to improve access to frozen section consultation.^5,31-33 Benefits to improving access to frozen section include providing frozen section consultation at remote or off-site locations, increasing access to subspecialty consultation, improving workflow by eliminating the need to travel off-site to the frozen section case, cost savings in staff work time, and providing educational opportunities for pathology trainees.^5,31-33 In our experience, WSI with real-time viewing of frozen section allows for the assessment of transplant tissues, which is an evaluation that generally occurs at night. Discrepancies from frozen section telepathology using WSI to the final diagnosis may occur and those specific to WSI could result from slide or image quality, internet connectivity, and lack of training in using the telepathology system.³² Other issues that may lead to discrepancies between the frozen section diagnosis and the final diagnosis may occur with the review of glass slides by light microscopy.³⁴ Appropriate performance of validation, training, implementation, and quality control for telepathology can help in reaping the benefits while mitigating the risks.² In a large study comparing frozen section evaluation by telepathology with light microscopy, the sensitivity and specificity of frozen section were comparable between telepathology and light microscopy with a trend toward greater sensitivity by telepathology (0.92 and 0.99 for telepathology vs 0.90 and 0.99 by light microscopy alone, sensitivity and specificity, respectively).³³

Other applications. Evidence for efficacy in surgical pathology diagnosis led to FDA approval of the Philips IntelliSite Digital Pathology in 2017 and the Leica Aperio AT2 DX in 2020 WSI platforms.^6-8 The use of WSI in surgical pathology has been successfully validated or used in clinical practice at several pathology laboratory settings with documented benefits in the literature for primary and secondary diagnoses, QA, research, and education.^6-8,35-45 Benefits of telepathology include improved ergonomics and access to real-time pathologic services in remote areas or during on-site pathologist absence and expert second opinions. Telepathology also may reduce risk of slide loss during transport, shortened turnaround time, reduced costs of operation through workflow efficiencies, better load balancing, improve virtual collaboration, and digital storage of slides that may be irreplaceable.^3-8,35-45 Telepathology also has been shown to be useful for education, improving access to learning materials and increasing quality instructional materials at a lower cost.⁴⁵ The increased ease of collaboration with remote experts and access to slide material for other pathologists improves QA capabilities.^3-8,35-45 The availability of virtual slides is expected to promote further research in telepathology and pathology due to the increased availability of virtual material to researchers.^1,5,46

Telehematology. Published validations have shown effectiveness for hematopathology specimens, such as the peripheral smear. Telehematology also has demonstrated potential in a laboratory after proper validation and implementation as a laboratory-developed test.^37,47-49

Telemicrobiology and Computer-Assisted Pathologic Diagnosis. Telemicrobiology also has been successfully used for clinical, educational, and QA purposes.⁵⁰ The digitalization of slides involved with telepathology enables further innovation in machine learning for computer-assisted pathologic diagnosis (CAPD), which is already being used clinically for cervical Pap smears.²⁰ An artificial intelligence (AI)–based algorithm analyzes the slides to identify cells of interest, which are presented to the cytopathologist for confirmation.²⁰ However, the expansion of CAPD to include a variety of specimen types or diagnostic situations as well as safely and effectively take initiative in completing an accurate automated diagnosis requires additional development.^20,51,52 One of the key factors for machine learning to develop AI is the provision of a corpus of data.^51,52 Public, open-source data sources have been limited in size while private proprietary sources have highly restricted and expensive access; to address this, there is a current effort to build the world’s largest public open-source digital pathology corpus at Temple University Hospital, which may help enable innovations in the future.⁵²

Long-Term Trends/Applications

The COVID-19 pandemic has been unprecedented not only in its widespread morbidity and mortality, but also for the significant socioeconomic, health, lifestyle, societal, and workspace changes.^53-57 Specifically, the pandemic has introduced not only a need for social distancing and staff quarantines to prevent the spread of infection, but also a reduction in the workforce due to the stresses of COVID-19 (also known as the Great Resignation).⁵⁵ Before the pandemic, there was an existing downtrend in the number of pathologists in the US workforce.^9-10,58,59 From 2007 to 2017, the number of active pathologists in the US declined by 17.5% despite the increasing national population, resulting in not only an absolute decrease in the number of pathologists, but also an increasing population served per pathologist ratio.⁵⁹ Since 2017, this downtrend has continued; given the increasing loss of active pathologists from the workforce and the decreasing training of new pathologists, this decrease shows no signs of reversing even as the impact of the COVID-19 pandemic has begun to wane.^9,10,58-60

The advantages of telepathology in enabling social distancing and reducing travel to remote sites are known.^3-7,17 Given these advantages, some medical centers in the US have previously successfully validated and implemented telepathology operations earlier during the COVID-19 pandemic to ease workflow and ensure continued operations.^56,57 The use of telepathology also helps in balancing workload and continuing pathology operations even in light of the workforce reduction as cases no longer need to be signed out on site with glass slides but instead can be signed out at a remote laboratory. Although the impact of the COVID-19 pandemic on operations is decreasing, the capabilities for social distancing and reducing travel remain important to both improve operations and ensure resiliency in response to similar potential events.^3-7,17,60

Considering the long-term trends, the lessons of the COVID-19 pandemic, and the potential for future pandemics or other disasters, telepathology’s validation and implementation remains a reasonable choice for pathology practices looking to improve. A variety of practices not just in the general population, but also among US Department of Veterans Affairs medical centers (VAMCs) and the US Department of Defense Military Health System treating a veteran population can benefit from telepathology where it has previously been reported to have been reliable or successfully implemented.^61-63 Although the veteran population differs from the general population in several characteristics, such as the severity of disease, coexisting morbidities, and other history, given proper validation and implementation, telepathology’s usefulness extends across different pathology practice settings.^35-43,61-66

Limitations of Telepathology

In telepathology’s current state, there are limitations despite its immense promise.^6,35 These include initial capital costs, the additional training requirement, the additional time necessary to scan slides, technical challenges (ie, laboratory information system integration, color calibration, display artifacts, potential for small particle scanner omissions, and information technology dependence), the potential for slower evaluation per slide compared with optical microscopes, limitations of slide imaging (ie, z-stacking or lack of polarization on digital pathology), and occupational concerns regarding eye strain with increased computer monitor usage (ie, computer vision syndrome).^6,35 In addition, there are few telepathology scanners with FDA approval for WSI.^6-8

The improving technology of telepathology has made these limitations surmountable, including faster slide scanning and increasing digital storage capacity for large WSI files. Due to this improvement in technology, an increasing number of laboratory settings, have adopted telepathology as its advantages have begun to outweigh the limitations.^2-5 Additionally, the proper validation performed before implementing telepathology can help laboratories identify their unique challenges, troubleshoot, and resolve the limitations before use in clinical care.^11-13 Continuing QA during its use and implementation is important to ensure that telepathology performs as expected for clinical purposes despite its limitations.²

Conclusions

Telepathology is a promising technology that may improve pathology practice once properly validated and implemented.^1-8 Though there are barriers to this validation and implementation, particularly the capital costs and training, there are several potential benefits, including increased productivity, cost savings, improvement in the workflow, enhanced access to pathologic consultation, and adaptability of the pathology laboratory in an era of a decreased workforce and social distancing due to the COVID-19 pandemic.^1-8,55-56 This potential applies across the wide spectrum of potential telepathology uses from frozen section, telecytology (including ROSE) to primary and second opinion diagnoses.^1-8,17-33 The benefits also extends to QA, education, and research, as diagnoses can not only be rereviewed by specialty or second opinion consultation with ease, but also digital slides can be produced for educational and research purposes.^3-8,35-45 Settings that treat the general population and those focused on the care of veterans or members of the armed forces have reported similar reliability or successful implementation.^35-44,61-63 All in all, the use of telepathology represents an innovation that may transform the practice of pathology tomorrow.